HIV infection: Risk factors and prevention
strategies
Author:
Section Editor:
Myron S Cohen, MD
Roy M Gulick, MD, MPH
Deputy Editor:
Jennifer Mitty, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2022. | This topic last updated: Sep 20, 2021.
INTRODUCTION
Although the incidence of HIV has dropped
considerably since the height of the epidemic, millions of new HIV infections occur
globally each year. An understanding of the risk factors for HIV infection lies at the
foundation of successful preventive strategies, which should combine both
behavioral and biomedical interventions to reduce HIV infection risk.
This topic reviews these risk factors and prevention strategies. More detailed
discussion on particular prevention strategies, including pre- and postexposure
prophylaxis for HIV, and prevention of mother-to-child transmission of HIV are
found elsewhere. (See "Administration of pre-exposure prophylaxis against HIV
infection" and "Management of nonoccupational exposures to HIV and hepatitis B
and C in adults" and "Management of health care personnel exposed to
HIV" and "Antiretroviral selection and management in pregnant women with HIV
in resource-rich settings" and "Prevention of mother-to-child HIV transmission in
resource-limited settings".)
MODES OF ACQUISITION
HIV infection is acquired through sexual
intercourse, exposure to infected blood, or perinatal transmission. The distribution
of the modes of transmission of HIV infection varies in different countries. In the
United States, male-to-male sexual contact and injection drug use (IDU) account
for more than half of cases [1]. The estimated lifetime risk of an HIV diagnosis in
the United States is 1 in 6 for all men who have sex with men (MSM), 1 in 2 for
African American MSM, 1 in 4 for Latino MSM, 1 in 23 for women with IDU, and 1 in
36 for men with IDU, in contrast to 1 in 241 and 1 in 473 for heterosexual women
and men, respectively [2,3].
In contrast, in some resource-limited areas, penile-vaginal intercourse is
responsible for the majority of HIV infections, with a smaller but growing
proportion of cases among MSM [4]. Stigma remains a major problem hindering
the study of MSM in resource-constrained countries; the incidence and prevalence
of HIV in MSM in these settings warrant greater attention. (See "Global
epidemiology of HIV infection", section on 'Modes of transmission driving the
epidemic'.)
RISK FACTORS FOR INFECTION
Risk of HIV infection varies by type of
sexual or parenteral exposure (table 1). However, estimates of risk are mostly
based on observational studies and are difficult to quantify since transmission risk
also depends on other cofactors that greatly enhance (and occasionally reduce)
the probability of infection [5-7]. As an example, risk factors for HIV transmission
include high viral load in the source patient, and risk factors for HIV acquisition
after exposure include sexually transmitted infections (STIs), and lack of
circumcision, as well as certain host and genetic factors [8-10].
Infectiousness of source
Viremia in the source individual and acute HIV — For all modes of transmission,
a higher viral load in the source individual living with HIV is associated with a
greater risk of transmission. Viral load depends on several factors, most
importantly whether the individual is taking antiretroviral therapy (ART) and the
stage of HIV disease [5,11,12]. Individuals with stable viral suppression
demonstrate no risk for HIV transmission [11,13-18]. Conversely, the risk of HIV
transmission appears higher during acute infection, when HIV infection is
unrecognized and maximal viremia is present [5,19]. Phylogenetic and modeling
studies (further discussed below) have highlighted that transmission from acutely
infected individuals contributes disproportionately to the spread of HIV.
In studies of heterosexual couples, those who transmit HIV have higher levels of
HIV RNA than those who do not transmit HIV [5,8,20,21]. As an example, in a study
of 415 HIV-serodiscordant couples in Uganda, the baseline serum viral load was
higher among transmitting partners than non-transmitting partners (90,000 versus
38,000 copies/mL, respectively) [8]. For each log increase in viral load, there was a
2.5-fold increase in the risk of transmission. In contrast, there were no HIV
transmission events from partners living with HIV whose baseline viral load was
<1500 copies/mL, suggesting a threshold viral level for transmission [8].
Accordingly, higher viral load in the genital secretions also increases the
probability of HIV transmission [20]. Similar findings have been described for
perinatal HIV transmission. (See "Antiretroviral selection and management in
pregnant women with HIV in resource-rich settings", section on 'HIV viremia and
risk of infant infection'.)
The viral load can be very high in patients with acute HIV infection or in those with
advanced untreated AIDS [22]. Acute infection is also associated with increased
viral shedding in genital secretions for several weeks after infection compared with
the stable lower levels seen in chronic infection [23]. Accordingly, in several
studies, the risk of transmission of HIV appears highest from patients with acute
HIV infection and higher from patients with late-stage disease (ie, AIDS) compared
with chronic infection [22,24-28]. One modeling study estimated that 38 percent of
all HIV transmissions in Malawi were attributable to sexual contact with acutely
infected individuals [24]. A phylogenetic analysis of patients with acute and early
HIV infection, including mostly men who have sex with men, was similarly
suggestive of transmission networks during early infection, with evidence of
infection with viruses that could be grouped into closely related clusters [25,26].
Additionally, some animal data also support an increase in viral infectivity during
newly-acquired infection [29].
Virus in genital fluids — In general, lower levels of blood plasma HIV RNA are
associated with decreased genital HIV RNA levels [20]. Several studies have shown
that HIV can still be intermittently detected in seminal fluid of some men living
with HIV, despite suppression of HIV viremia with ART [30-34]; this has been
associated with concurrent STI, such as urethritis [33]. HIV can also often be
detected in the vaginal secretions of women despite the use of ART that
suppresses replication in blood [35,36]. However, when plasma RNA is suppressed,
detectable viral RNA in genital fluids likely does not represent replicationcompetent virus capable of transmission. Several studies among women and men
have demonstrated that treatment-induced viral suppression in the blood
eliminates the risk of transmission. These studies are discussed in detail
elsewhere. (See 'Treatment as prevention' below.)
Source with unknown HIV status — Often the HIV status of the sexual or
injecting partner is unknown. The probability of HIV acquisition from a source
person whose HIV status is unknown is approximated by estimating the likelihood
that the source has HIV multiplied by the likelihood of transmission. As an
example, in the United States, the prevalence of HIV infection in men aged 18 to 39
in the NHANES study (2003 to 2006) was 0.43 percent [37]. Thus, the estimated risk
of transmission following a single random episode of receptive vaginal intercourse
in the United States would be approximated by multiplying 0.0043 times 0.001 for
an estimate of 0.0000043 (ie, 1 in approximately 233,000).
However, specific information about the source may increase the likelihood that he
or she is living with HIV (eg, a history of injection drug use). Furthermore, such
calculations are completely different in parts of the world, such as many parts of
sub-Saharan Africa, where HIV infection is far more prevalent.
Sexual transmission risk factors — The exact risk of transmission of HIV with
sexual exposure is incompletely defined [5,6,38]. However, the data do suggest
that risk of HIV acquisition varies by type of exposure (ie, sexual acts) [39-44].
The risk of acquiring HIV after rape by an unknown assailant depends on many
factors specific to the assault. This issue is discussed in detail elsewhere.
(See "Evaluation and management of adult and adolescent sexual assault
victims".)
Sexual behavior — The risk of HIV transmission varies widely depending on the
type of sexual exposure. In general, exposures that lead to mucosal disruption and
bleeding are associated with higher risk than other exposures. Unprotected anal
intercourse conveys the greatest probability of sexual transmission of HIV [38].
Other behavioral factors, such as whether condoms were used, the number of
sexual partners, or sex under the influence of recreational drugs, also affect the
overall risk of HIV infection. As an example, in a study of 3257 men who have sex
with men (MSM) in six US cities, risk factors for HIV acquisition included history of
a large number of sexual partners, unprotected receptive anal sex with a partner
with an unknown HIV serostatus, and use of nitrate inhalants [45]. In sub-Saharan
Africa, having a male sexual partner of older age is a risk of HIV acquisition among
young women [46].
The risk of HIV transmission for different types of sexual exposure to HIV in
discordant couples has been estimated using different methods (generally
through modeling studies) and cohorts (table 1) [47]
●Receptive anal intercourse – One transmission per 72 sex acts
●Insertive anal intercourse – One transmission per 900 sex acts
●Receptive penile-vaginal intercourse – One transmission per 1250 sex
acts
●Insertive penile-vaginal intercourse – One transmission per 2500 sex
acts
●Receptive or insertive penile-oral sex – Zero to four transmissions per
10,000 sex acts
However, these risk estimates make it difficult to understand the magnitude of the
HIV pandemic. Clinicians need to be aware that such estimates of risk are often
based on studies of monogamous couples, among whom amplifying factors have
been treated and repeated exposure may offer as yet unexplained protection from
infection. There are scant empiric data on per contact risk of exposure.
Additionally, differences in infectivity are also strongly influenced by the presence
of other cofactors, such as concomitant genital ulcerative disease [5]. As an
example, some models suggest that rates of HIV transmission may be as high as
one transmission event for every three episodes of insertive anal sex between a
male source with late-stage disease and a susceptible female with genital
ulcerative disease [48]. Thus, using a single value for assessing risk of HIV
transmission based on route of sexual exposure fails to reflect the variation
associated with other important cofactors.
HIV transmission among MSM is generally higher than among heterosexual
partners. Among heterosexual partners, male-to-female transmission may be
slightly more common (ie, efficient) than female-to-male transmission, as
observed for most STIs. The relative risk of male-to-female compared with femaleto-male HIV transmission was well illustrated in one study of 563 HIV
serodiscordant couples (including 156 females living with HIV and 400 males living
with HIV), in which 19 male partners and 82 female partners acquired HIV during
the course of observation [49]. This study suggested that male-to-female
transmission was 1.9 times more efficient (95% CI 1.1-33) than female-to-male
transmission.
Notably, female-to-female sexual transmission of HIV has only rarely been
reported [50,51].
Lack of circumcision — HIV acquisition rates among uncircumcised males are
higher than for circumcised males. The biologic basis for this observation may be
related to a high density of HIV target cells in male foreskin, including Langerhans
cells and macrophages [52]. Randomized controlled trials in Africa have
demonstrated that circumcision reduces the risk of female-to-male HIV
transmission by 50 to 60 percent [53-56], and this benefit is sustained [56].
However, male circumcision of men living with HIV does not appear to decrease
the risk of HIV transmission to the female partner, and efficacy in men who have
sex with men has not been demonstrated. (See 'Male circumcision' below.)
Sexually transmitted infections — Concurrent sexually transmitted infections
(STIs) have been long known to increase the risk of both acquiring and
transmitting HIV infection. The increased risk is widely acknowledged for STIs that
cause genital ulcer disease but is also described with other STIs [57]. It has also
been associated with the change in vaginal flora that characterizes bacterial
vaginosis [58,59] and dysbiosis [60]. In particular, risk of HIV acquisition has been
linked to specific inflammatory cytokine profiles evoked by STIs [19] and certain
bacterial species that may compromise prevention strategies [61].
Several studies have demonstrated an increased incidence of HIV infection among
patients with genital ulcerative diseases, such as herpes simplex virus and syphilis
[22,62,63]. As an example, in a study of 174 monogamous Ugandan couples with
discordant HIV serostatus, the probability of transmission was approximately four
times higher in patients with genital ulceration compared to those without [22].
The effect of these infections on HIV risk is discussed in detail elsewhere.
(See "Epidemiology, clinical manifestations, and diagnosis of genital herpes
simplex virus infection", section on 'HSV-2 and risk of HIV
transmission' and "Syphilis in patients with HIV", section on 'Effect of syphilis on
HIV'.)
Increased risk of HIV is not limited to STIs that cause genital ulcer disease. In a
prospective study of 242 South African women with high-risk sexual behavior, 28
became infected with HIV over 24 months [64]. Presence of a concurrent STI was
associated with an increased risk of infection with HIV (hazard ratio [HR] 3.29, 95%
CI 1.5-7.2). The incremental risk for HIV infection with Neisseria
gonorrhoeae infection was greater than that with other infections (Chlamydia
trachomatis, Mycoplasma genitalium, Trichomonas vaginalis). The majority of women
with STIs were asymptomatic.
Among people with HIV infection, STIs may increase HIV shedding in genital
secretions in spite of suppression of viremia with ART [65-67]. However, viral
copies recovered are not likely to be replication competent.
Genetic background — Similarity of HLA-class-I alleles between HIV discordant
couples may affect the risk of transmission by resulting in selected viral strains
that are more likely to escape the immune containment of the uninfected partner.
In a study of serodiscordant couples, sharing of HLA-B alleles was associated with
accelerated transmission of HIV after controlling for other variables (HR 2.23, 95%
CI 1.52 to 3.26) [10] (see "Human leukocyte antigens (HLA): A roadmap"). The most
profound effects are mediated by the homozygous deletion of the CCR5 receptor
[68]. People with this genetic variation are resistant to HIV because the CCR5
receptor is critical to HIV acquisition. Two patients who underwent bone marrow
transplants with CCR5 deleted stem cells were cured of HIV infection,
demonstrating the critical importance of this receptor [69-71]. (See "The natural
history and clinical features of HIV infection in adults and adolescents", section on
'Alterations in the CCR5 coreceptor'.)
Hormonal contraceptive use — Early studies raised concern that certain
hormonal contraceptive methods, specifically depot medroxyprogesterone
acetate (DPMA), might increase the risk of HIV acquisition. However, subsequent
data suggest no increased risk of HIV among women using DMPA or other
contraceptives. These studies are discussed in detail elsewhere. (See "HIV and
women", section on 'Risk factors for HIV acquisition'.)
Other factors — Studies observing higher incidence of HIV acquisition during late
pregnancy and the postpartum period suggest the possibility that physiologic
changes during pregnancy affect susceptibility to HIV infection [72,73]. There has
also been increased interest in defining specific vaginal fluid cytokine profiles that
are associated with and could serve as a marker for increased risk of HIV infection
[74,75].
Bloodborne transmission risk factors — The risk of transmission of HIV infection
following inadvertent exposure varies widely depending upon the type of
exposure.
The risk of HIV infection has been estimated for different types of bloodborne
exposure to a source with HIV (table 1) [7,76,77]:
●Blood transfusion – nine infections per 10 exposures
●Needle or syringe sharing – one infection per 150 exposures
●Percutaneous needle-stick – one infection per 435 exposures
●Mucous membrane exposure to blood (eg, splash to eye) – one
infection per 1000 exposures
●Other exposure (eg, human bite) – one infection per 25,000
exposures
Studies on needlestick injuries in the health care setting have identified certain
characteristics of injury that are associated with increased risk of HIV infection [78].
These include a deep injury, injury with a device that was visibly contaminated with
the source individual's blood, injury with a needle that had been placed in a vein or
artery, and terminal illness in the source individual. The volume of blood
contributes to the probability of transmission since the reported risk of HIV
acquisition after transfusion with a contaminated unit of blood ranges from 88 to
100 percent [7]. With the current screening procedures for donated blood, this risk
is vanishingly small (see "Blood donor screening: Laboratory testing", section on
'HIV-1 and HIV-2'). In the United States, between 2000 and 2013, there has only
been a single confirmed case of occupationally-acquired HIV infection among
health care personnel, in a laboratory technician who had a needle puncture while
working with live HIV culture [79].
The risk of HIV may be higher among individuals who inject drugs than is reflected
by the risk of needle sharing. Many individuals who use injection drugs also
participate in sexual behavior, such as unprotected sex and sex with multiple
partners, that incrementally increases the risk for HIV infection [80].
Perinatal transmission risk factors — This is discussed in detail elsewhere.
(See "Antiretroviral selection and management in pregnant women with HIV in
resource-rich settings" and "Prevention of mother-to-child HIV transmission in
resource-limited settings".)
EFFICACY OF PREVENTION STRATEGIES
Postexposure prophylaxis — For individuals who have a discrete high-risk
exposure to HIV, postexposure prophylaxis with an antiretroviral-based regimen is
an effective strategy to reduce the risk of infection. This is discussed in detail
elsewhere. (See "Management of health care personnel exposed to
HIV" and "Management of nonoccupational exposures to HIV and hepatitis B and
C in adults".)
Pre-exposure prophylaxis — For individuals who are at ongoing high risk for HIV
infection, pre-exposure prophylaxis with an antiretroviral-based regimen is an
effective strategy to reduce the risk of infection. Pre-exposure prophylaxis is
discussed in detail elsewhere. (See "Administration of pre-exposure prophylaxis
against HIV infection".)
Treatment as prevention — Treatment as prevention refers to the concept that
successfully treating HIV with antiretroviral therapy (ART) minimizes the risk of
transmission by decreasing the HIV plasma viral load, and it assumes the potential
of a population level benefit.
Several studies have indicated that the risk of transmission to an uninfected sexual
partner is negligible when an individual living with HIV has achieved durable viral
suppression with ART [81]. This was best demonstrated in a large trial (HPTN 052)
that included 1763 HIV serodiscordant heterosexual couples from 13 sites in 9
countries in Africa, Asia, South America, and North America [12,82]. The
serodiscordant couples were randomly assigned to an "early ART" arm (initiation
of HIV treatment at enrollment) or "delayed ART" arm (initiation of HIV treatment
when the CD4 count dropped to less than 250 cells/microL or after an AIDS-related
illness). ART consisted mainly of zidovudine, lamivudine, and efavirenz. After 1.7
years of follow-up, interim analysis demonstrated that early ART substantially
reduced the risk of HIV transmission to the partner compared with delayed ART (1
versus 27 linked transmissions, as determined by viral sequencing; hazard ratio
[HR] 0.04, 95% CI 0.01-0.26). Following these results, ART was offered to the
participants living with HIV in the delayed ART group who had not yet initiated it;
by the end of the study, 96 percent of the delayed group had started on ART. After
a median of 5.5 years and 8904 couple-years of follow-up, the prevention benefits
were sustained:
●A total of 46 linked transmissions were identified. Three occurred in
couples originally assigned to the early ART group compared with 43
in the delayed ART group (93 percent risk reduction with early ART). A
total of eight linked transmissions occurred after the partner living
with HIV had initiated ART, but they either occurred within three
months of ART initiation or in the setting of ART failure. Thus, no
linked transmission events occurred when the partner living with HIV
had achieved stable viral suppression on ART.
●There were an additional 16 HIV infections in each group. Of these,
14 in the early ART group and 12 in the delayed ART group were
determined by viral sequencing to be genetically unlinked (ie, the
source was not the individual's documented partner). An additional
six infections (two in the early ART and four in the delayed ART group)
could not be sequenced for technical reasons.
●Overall, the incidence of HIV infection in the study was low (0.9
percent per year overall and 2.2 events per 100 person years in the
delayed ART group at the interim analysis), which potentially reflects
other risk reduction strategies in this study. All participants received
condoms and risk reduction counseling. Complete adherence to
condom use was independently associated with a reduced risk of both
linked and unlinked HIV infections.
The efficacy of ART in reducing the risk of HIV transmission to an uninfected sexual
partner has also been supported by many observational studies among
heterosexual discordant couples [13,14,83-91]. As an example, in a large
retrospective study of almost 39,000 such couples in China, the incidence of HIV
infection among uninfected partners was lower if the infected partner was on ART
versus untreated (1.3 versus 2.6 infections per 100 person years, respectively,
adjusted HR 0.74, 95% CI 0.65–0.84) [85]. Similarly, in a large population-based
prospective cohort study of individuals without HIV in rural KwaZulu-Natal, South
Africa, where transmission is predominantly through heterosexual sex, HIV
infection risk was lower in communities with high ART coverage compared with
areas of low ART coverage [92]. Such ecological studies, which examine
relationships between exposures and outcomes at the group level, have a number
of methodological challenges, including selection bias, confounding, and
assumptions about the time lag of effects, which limit the ability to link the
exposure to the outcome for the individual [86,93]. Nevertheless, these results
indicate the importance of ART as a prevention strategy.
Although most studies of treatment as prevention have included condom use
counseling as part of the preventive strategy, studies evaluating serodiscordant
couples who specifically do not use condoms also suggest that successful ART
prevents transmission [14-16]. As an example, in a prospective observational study
of serodiscordant (548 heterosexual and 340 men who have sex with men [MSM])
couples who chose not to use condoms and among whom the partner living with
HIV was virally suppressed on ART (<200 copies/mL), there were no documented
intra-couple transmission events after more than 1200 couple-years of follow-up
[14]. One heterosexual and 10 MSM partners acquired HIV infection during the
study period, but viral sequence analysis suggested that these infections were not
transmitted from the long-term partner living with HIV.
The efficacy of treatment as prevention is also reflected in the reduction in the rate
of mother-to-child transmission of HIV with successful ART of the mother during
pregnancy and delivery. (See "Antiretroviral selection and management in
pregnant women with HIV in resource-rich settings", section on 'Efficacy of ART in
preventing transmission' and "Prevention of mother-to-child HIV transmission in
resource-limited settings", section on 'Efficacy of maternal ART in preventing
transmission'.)
Data on the efficacy of ART to prevent transmission in populations at risk for other
modes of transmission (ie, MSM or injection drug users) are more limited:
●Several
observational studies have suggested that ART prevents
sexual transmission among MSM [14-16]. As an example, in a study of
nearly 800 serodiscordant MSM couples in Europe, of which the
partner living with HIV was virologically suppressed (viral load <200
copies/mL) on ART, there were no linked transmissions over 1500
couple-years, which included over 76,000 condomless sex acts [16].
Over a third of men without HIV reported sex outside the partnership,
and 15 incident unlinked infections were detected. Similarly, a study of
nearly 350 MSM serodiscordant couples in Australia, Thailand, and
Brazil did not detect any linked transmission over 232 couple-years,
during which the infected partner was on suppressive ART (with a
viral load <200 copies/mL) [15].
●In a study of people who inject drugs in Indonesia, Vietnam, and the
Ukraine, accelerated ART and substance use management reduced
mortality and reduced HIV transmission among injection partners
compared with standard of care (0 versus 7 incident infections, which
were likely transmission events) [94].
Test and treat — Given the impact of ART in eliminating HIV transmission
between serodiscordant couples, there has been substantial interest in a strategy
of early ART initiation upon diagnosis as a way to reduce community HIV incidence.
Modeling studies have suggested that this "test-and-treat" strategy could
significantly reduce HIV transmission in high prevalence countries [95-97], but
randomized trials have yielded mixed results, with most demonstrating modest
decrease in HIV incidence between intervention and control arms [98-101]. Trial
interventions have included combinations of enhanced HIV testing, linkage to care,
ART initiation, and adherence support. The magnitude of benefit at the population
level requires complex interpretation. Some illustrative trials include the following:
●In a trial in rural Uganda and Kenya (SEARCH Trial) that included over
150,000 participants, communities were randomly assigned to annual
HIV testing with rapid ART initiation for those who test positive
(intervention) compared with baseline HIV testing and ART
administration according to national guidelines (control) [100]. All
testing was performed in the setting of multi-disease public health
fairs that also addressed hypertension and diabetes mellitus. The
intervention resulted in higher rates of viral suppression (79 versus 68
percent at three years) and reduced mortality among individuals
living with HIV (relative risk 0.77). However, it did not reduce the
three-year cumulative incidence compared with the control group
(0.77 versus 0.81 percent, relative risk 0.95, 95% CI 0.77-1.17); across
both groups, annual HIV incidence decreased by 30 percent over
three years. Marked improvement in the standard of care available to
the control group over the course of the trial likely compromised the
differences between groups.
●In a trial in Zambia and South Africa (PopART Trial) with greater than
48,000 participants, communities were randomly assigned to standard
care or a prevention intervention of annual home-based HIV
counseling and testing, linkage to care and adherence support for
those who test positive, and encouragement of male circumcision
[101]. Those in the prevention intervention group were further
randomly assigned to universal ART or ART initiation according to
local guidelines. Both intervention arms had increased rates of viral
suppression compared to the standard care arm; however, only the
intervention arm with ART provided per local guidelines had a lower
HIV incidence compared with standard care (adjusted rate ratio for
HIV incidence 0.70 [95% CI 0.55-0.88]). The reduction in HIV incidence
with the prevention intervention and universal ART compared with
standard care was lower in magnitude and not statistically significant
(adjusted rate ratio 0.93 [95% CI 0.74-1.18]). When the two
intervention arms were combined, there was a 20 percent decrease in
HIV incidence relative to control communities. The explanation for the
difference in HIV incidence reduction between the two prevention
intervention groups is unclear.
●A trial in rural and semi-urban areas in Botswana (Ya Tsie Trial) that
included over 12,000 participants also demonstrated a 35 percent
reduction in HIV incidence (0.59 versus 0.92 percent per year,
incidence rate ratio 0.65, 95% CI 0.46-0.90) with annual HIV testing,
enhanced linkage to care with early ART initiation, and
encouragement of male circumcision [99].
Further analyses of cost-effectiveness and projected population impact are also
ongoing. These studies emphasize the degree of difficulty in treating the right
people at the right time with the right drugs to get the maximal benefit of
treatment as prevention. Untreated acute and early HIV transmission and
migration of people off ART can be expected to lead to HIV transmission at a rate
that would compromise the population benefit of a "Test and Treat" strategy.
However, population surveys in African countries have demonstrated strong
correlation between expansion of treatment of HIV and falling incidence of HIV
infection [102].
Condom use — Consistent condom use effectively decreases the risk of sexual HIV
transmission and acquisition [103-106]. In 2009, a collaborative statement from the
American College of Physicians and the HIV Medicine Association called for wider
availability of condoms and education about their proper use to minimize the risk
of HIV transmission [106]. In order for condom use to be effective in decreasing
HIV prevalence, they need to be used consistently and with ongoing exposures,
particularly in areas of high prevalence.
The majority of evidence for condom effectiveness is from observational studies.
In a meta-analysis of 12 studies of HIV heterosexual serodiscordant couples,
condom usage was classified in three categories: always, sometimes, or none
[103]. HIV infection rates were much higher in those who never used condoms
versus those who always did (6.7 versus 0.9 infections per 100 person years). A
subsequent analysis of these studies suggested that condoms are 90 to 95 percent
effective when used consistently [107]. A similar Cochrane review estimated that
the consistent use of male latex condoms, defined as using a condom for all acts of
penetrative vaginal intercourse, reduces HIV incidence by 80 percent, based on
several longitudinal female-to-male and male-to-female serodiscordant couples
[105]. Additionally, in a trial of ART to reduce HIV transmission within
serodiscordant couples, a self-report of "100 percent use" of condoms compared
with "less than 100 percent use" was associated with decreased HIV transmission
(HR 0.35; 0.14-0.88) [82]. These clinical studies are consistent with the in vitro
finding that latex and polyurethane condoms are impenetrable to HIV viral
particles [108].
Since women are often unable to convince their partners to use a condom, there is
a need to assess other barrier methods that women can initiate. Female condoms
are also impervious to viruses, including HIV; however, there are few clinical data
regarding efficacy in prevention of HIV transmission [109].
Male circumcision
HIV infection in heterosexual men — Male circumcision reduces the risk of
heterosexual men becoming infected with HIV. Voluntary male medical
circumcision is generally safe, but rare cases of tetanus following circumcision
have been reported in locations where uptake of infant tetanus immunization is
low [110,111]. (See "Tetanus".)
The efficacy of male circumcision to protect that male against HIV infection has
been established by several randomized, controlled trials of circumcision
conducted in Africa [53-55]. In these trials, men were randomly assigned to an
intervention group, in which immediate circumcision was offered, or a control
group, in which circumcision was delayed until the end of the study. In all cases,
circumcisions were performed by clinicians experienced in the procedure and were
rarely associated with moderate or severe adverse effects. These three trials were
all ended early because of evidence of reduced HIV incidence in the intervention
groups:
●In a trial in Orange Farm, South Africa, circumcision reduced the risk
of HIV infection by 60 percent among 3274 men aged 18 to 24 years
(20 versus 48 new infections in the circumcision and control groups,
respectively, after a mean follow-up of 18 months) [53]. The
investigators controlled for behavioral factors, condom use, and
health-seeking behaviors.
●In a trial in Kisumu, Kenya, circumcision reduced the risk of HIV
infection by 53 percent among 2784 men aged 18 to 24 years (22
versus 47 new infections in the circumcision and control groups,
respectively, after a median follow-up of 24 months) [54].
●In a trial in Rakai, Uganda, circumcision reduced the risk of HIV
infection by 51 percent among 4996 men aged 15 to 49 years (0.66
versus 1.33 new infections per 100 person years in the circumcision
and control groups, respectively, over 24 months) [55]. Following trial
closure, the majority of uncircumcised men underwent circumcision.
After five years, circumcision remained associated with a lower HIV
risk (0.5 versus 1.93 new infections per 100 person years in
circumcised and uncircumcised men, respectively) [56].
Population studies in Africa following wider availability and encouragement of
voluntary medical male circumcision have also suggested an association between
circumcision and reduced incidence of HIV infection and have continued to
demonstrate safety of the practice [91,112-114].
Data from the United States are limited. One study examined visit records of
heterosexual African-American men who underwent HIV testing while attending
STI clinics in Baltimore from 1993 to 2000 and analyzed the association between
circumcision and the risk of HIV infection [115]. "Known" HIV risk was defined as
patient notification by either their sexual partner or by an intervention specialist
from the partner notification system of recent HIV exposure. Among 394 visits by
patients with known exposure, circumcision was associated with lower HIV
prevalence (10.2 percent versus 22 percent; adjusted prevalence rate ratio, 0.49
[95% CI 0.26-0.93]). In the United States, however, the majority of sexually-acquired
HIV infections are among men who have sex with men (MSM), among whom
circumcision has uncertain benefit with regard to HIV risk. (See 'HIV infection in
MSM' below.)
Any policy to promote circumcision to protect against HIV infection needs to take
into account cultural and human rights considerations, the risk of complications
from the procedure performed in various settings, the prevalence of infection, and
the potential to undermine existing protective behaviors and prevention strategies
that reduce the risk of HIV infection [54,116]. Results from observational studies of
men who underwent circumcision suggest that this prevention intervention is not
necessarily offset by an adverse behavioral impact [117,118]. One study compared
sexual behaviors of 324 recently circumcised and 324 uncircumcised Kenyan men
at 1, 3, 6, 9, and 12 months after study enrollment [117]. Circumcised men did not
engage in more risky behaviors.
HIV infection in women — Although male circumcision reduces HIV acquisition in
men, studies have not demonstrated a reduction in HIV acquisition among female
sexual partners of men living with HIV who undergo circumcision. Results of these
studies suggest that HIV transmission from men to their sexual partners reflects
the HIV concentration in genital secretions (ie, semen) rather than exposure to the
uncircumcised glans penis.
In a trial from Uganda, 922 men living with HIV with CD4 cell counts ≥350 cells were
randomly assigned to immediate versus delayed circumcision for 24 months [119].
Circumcision did not reduce HIV transmission to the female sexual partners
without HIV; over a 24-month period, the cumulative probability of female
acquisition of HIV was 22 percent in the intervention group and 13 percent in the
control group (adjusted HR 1.49, 0.52-3.57). In addition, excess HIV transmission
occurred within the first six months in the male circumcision arm, particularly
among those who resumed intercourse prior to wound healing. These findings
suggest sexual abstinence or condom use should be strongly advised until surgical
recovery (estimated at six weeks).
HIV infection in MSM — To date, no randomized controlled studies of male
circumcision for HIV prevention have been conducted among men who have sex
with men (MSM). Observational studies have suggested a possible but uncertain
protective effect. Because some (but not all) MSM engage in both insertive and
receptive anal intercourse, it is difficult to conduct studies to show a benefit of
circumcision in this setting.
In a meta-analysis performed of 15 observational studies among 53,567 MSM (52
percent of whom were circumcised), the odds of having HIV were 14 percent lower
among the circumcised men, but the difference was not statistically significant
[120].
Counseling and harm reduction strategies — Risk-reduction counseling and
harm reduction strategies can reduce behavior that results in higher risk of HIV
infection. Risk-reduction counseling ranges from high-intensity behavioral
discussion tailored to an individual's risk to brief prevention messages to groupbased strategies [121,122].
Individuals report greater condom use and fewer sexual partners with behavioral
risk-reduction interventions, and some studies report that counseling decreases
risk of sexually transmitted infection (STI), including HIV [123,124]. The precise
efficacy of risk-reduction counseling may depend, in part, on how it is conducted.
(See "Prevention of sexually transmitted infections", section on 'Prevention
counseling'.)
For injection drug users, harm reduction interventions, such as voluntary opioid
substitution therapy and needle exchange programs, can reduce risky injection
behavior. Opioid substitution therapy is associated with decreased illicit opioid use,
injecting use, and sharing injection equipment [125]. Needle exchange or
supervised injection programs have also been associated with decreased needle
reuse and sharing, safe syringe disposal, and more hygienic injection practices
[126]. Although these strategies have not been evaluated in high-quality trials,
observational and modeling studies suggest that they are associated with
decreases in HIV infection [125,127,128]. Treatment of opioid addiction
with buprenorphine/naltrexone is also associated with increased use of and
adherence to ART among individuals living with HIV [129]. As noted above,
enhanced ART and substance abuse management have demonstrable personal
and public health benefits [94].
Treatment of sexually transmitted infections — "Classical" sexually transmitted
infections (STIs) that cause ulcers or mucosal inflammation are strongly associated
with HIV transmission [57]. However, it has been difficult to reliably demonstrate
the benefits of STI treatment for HIV prevention [130]. Screening and treatment of
STIs in at-risk individuals are important for general sexual health. (See "Screening
for sexually transmitted infections", section on 'Introduction'.)
Population-based studies have generally been unable to show a decrease in HIV
incidence with treatment or prevention of STIs [131,132]. It is generally concluded
that STI treatment to prevent HIV infection requires treatment of just the right STI
pathogen, at just the right time, with effective agents, goals that are not readily
achieved. Additionally, the findings in these studies may reflect problems with
methodology, patient adherence, and overlapping interventions in the control
group in these studies as opposed to a true lack of preventive benefit with STI
treatment [130].
Experimental approaches — A vaccine to prevent HIV infection has been an
elusive goal of HIV research. Despite several candidates, an effective HIV vaccine
has yet to be developed [133-135]. One vaccine tested in Thailand demonstrated
some short-lived protection from HIV, which was ascribed to antibody dependent
cytotoxicity [136].
More recently, discovery and characterization of antibodies that neutralize a large
number of strains of HIV have generated hope that such antibodies can be
delivered or generated in some way to provide long-acting prevention from HIV
[137-141].
Other experimental approaches include development of antiretroviral agents (eg,
long-acting forms) intended to improve outcomes with antiretroviral treatment or
pre-exposure prophylaxis. (See "Overview of antiretroviral agents used to treat
HIV" and "Administration of pre-exposure prophylaxis against HIV infection".)
CLINICAL APPROACH TO HIV PREVENTION
A comprehensive
approach to HIV prevention includes risk reduction among individuals living with
HIV to reduce transmission and among at-risk individuals to reduce acquisition.
Biomedical interventions (such as the antiretroviral-based strategies of treatment
as prevention and pre- and postexposure prophylaxis, as well as voluntary medical
circumcision for uninfected heterosexual males) are proven and highly effective in
reducing HIV infection. Nevertheless, behavioral interventions (such as condom
use and risk-reduction counseling) remain crucial elements of prevention, and
most studies of biomedical interventions included continued emphasis on
behavioral modification. While no single behavioral intervention is perfectly
effective, in aggregate, it is believed that such interventions have reduced the
spread of HIV in some populations. The magnitude of the epidemic without such
interventions cannot be predicted.
Accordingly, the following section discusses how certain aspects of biomedical and
behavioral interventions are combined for a patient-specific approach. This
discussion is generally consistent with recommendations on HIV prevention from
multiple expert organizations [142-144]. Discussion of the studies supporting the
individual prevention strategies is found elsewhere. (See 'Efficacy of prevention
strategies' above.)
Individuals living with HIV — Preventing transmission of HIV from individuals
living with HIV relies on engaging and maintaining patients living with HIV in care,
initiating antiretroviral therapy (ART) early, maintaining successful therapy, and
reducing behavioral risk factors.
Antiretroviral treatment — Suppression of plasma viremia with ART effectively
minimizes the risk of sexual [12,14,82,83] and perinatal HIV transmission and likely
does the same for other modes of transmission. Thus, ART is a key strategy to curb
the spread of HIV. (See 'Treatment as prevention' above.)
In the United States, ART initiation is recommended for all patients living with HIV,
regardless of CD4 cell count, to decrease AIDS and non-AIDS associated
morbidities and mortalities [142,144]. Prevention of HIV transmission is an
additional rationale for the more widespread use of ART. For resource-limited
settings, the World Health Organization (WHO) has also recommended ART
initiation for all patients living with HIV, regardless of CD4 cell count or clinical
stage, given the mounting evidence of the clinical benefit of ART, even at high CD4
cell counts [145,146], and the reduction in the risk of transmission to uninfected
partners with successful ART [147]. (See "When to initiate antiretroviral therapy in
persons with HIV" and "Use and impact of antiretroviral therapy for HIV infection
in resource-limited settings", section on 'Recommendations from the World Health
Organization'.)
Successful administration of ART relies upon public health measures to optimize
timely linkage of newly diagnosed individuals living with HIV with medical care and
retaining them in care. Treatment success also relies on patient adherence to
medication, which can be facilitated by reductions in pill burden, reduced dosing
frequency, and ongoing counseling to assess and encourage ART adherence.
Counseling on condom use — All patients living with HIV who are not on stable
ART should use condoms to reduce the risk of sexual transmission. For individuals
living with HIV with durable viral suppression on ART, the risk of transmission to an
uninfected sexual partner is negligible and use of condoms for the purpose of
preventing HIV transmission is no longer considered essential [12,83,148]. The
extensive data supporting treatment for prevention has led to the "U=U"
campaign, inspiring individuals living with HIV to recognize that "Undetectable"
HIV in the blood as a result of successful ART leads to an "Untransmissible" status
[17]. (See 'Treatment as prevention' above.)
Condoms do have other benefits, however, and we continue to advise their use in
certain situations, including:
●For
patients at risk for other sexually transmitted infections (STIs),
which are common among individuals living with HIV regardless of
ART, and which condoms effectively prevent [149]. (See "Prevention of
sexually transmitted infections", section on 'Male condom use'.)
●When a partner living with HIV has loss of virologic suppression, in
which case condoms can prevent against HIV transmission.
Risk reduction — Routine assessment of ongoing risk behavior should be
performed, and counseling on reducing those risks should be individualized.
For injection drug users, addiction treatment (eg, with opioid substitution or with
buprenorphine-naltrexone) and participation in needle exchange programs, if
available, are additional useful strategies to decrease risk behavior and, likely, HIV
transmission. (See 'Counseling and harm reduction strategies' above.)
Finally, we screen and treat STIs in individuals living with HIV given the increased
risk of STIs in this population, the association of STIs with HIV transmission, and
the benefit of treating STIs beyond potential HIV prevention [149]. (See 'Treatment
of sexually transmitted infections' above and "Screening for sexually transmitted
infections", section on 'Patients with HIV infection'.)
Individuals at risk for HIV
Identifying new infections — Identifying individuals living with HIV is crucial to
directing interventions to prevent transmission. Thus, HIV testing is a major
element of comprehensive preventive strategies. In particular, acutely infected
individuals, who often have exceptionally high levels of viremia, have been
identified as major sources of transmission (see 'Viremia in the source individual
and acute HIV' above). Testing strategies should employ diagnostic tests that are
highly sensitive for acute infection and should include routine screening for all
individuals with repeat testing of individuals with high ongoing risk for HIV.
(See "Screening and diagnostic testing for HIV infection".)
Once HIV infection has been diagnosed or excluded, preventive efforts for that
patient can be individualized. (See 'Individuals living with HIV' above and 'Risk
reduction' below.)
Risk reduction — In uninfected individuals, preventing acquisition of HIV focuses
on reducing behaviors that increase the risk of infection and utilizing
antiretroviral-based prophylactic strategies. In areas where the prevalence of HIV
is high and sexual transmission is primarily among heterosexuals, voluntary
medical circumcision is another important strategy.
All uninfected patients should be assessed for their risk of HIV infection, and
counseling on reducing those risks should be individualized.
●For
all patients at risk for HIV infection, we continue to advise
consistent condom use. (See 'Condom use' above.)
We also recommend screening and treatment of STIs in individuals at
risk for HIV given the shared risk factors for HIV and other STIs, the
association of other STIs with HIV infection, and the benefit of treating
STIs beyond potential HIV prevention [149]. (See 'Treatment of
sexually transmitted infections' above and "Screening for sexually
transmitted infections", section on 'Screening recommendations'.)
●For injection drug users, addiction treatment (eg, with opioid
substitution or buprenorphine-naltrexone) and participation in needle
exchange programs, if available, are additional useful strategies to
decrease risk behavior and, likely, HIV acquisition. (See 'Condom
use' above and 'Counseling and harm reduction strategies' above.)
●For those who have high ongoing risk for HIV infection, pre-exposure
prophylaxis effectively reduces the risk of infection. (See "Patient
evaluation and selection for HIV pre-exposure prophylaxis".)
●For those who have had a mucosal or parenteral exposure to HIV
within the prior 72 hours, postexposure prophylaxis with an
antiretroviral regimen is associated with a reduced risk of infection.
(See "Management of nonoccupational exposures to HIV and
hepatitis B and C in adults", section on 'Exposure to
HIV' and "Management of health care personnel exposed to HIV",
section on 'Post-exposure prophylaxis'.)
Circumcision has demonstrated efficacy in reducing the risk of HIV infection
among heterosexual men. WHO and the Joint United Nations Programme on
HIV/AIDS (UNAIDS) recommend scaling up voluntary male circumcision as a HIV
prevention intervention in several African countries with high rates of HIV and low
baseline rates of male circumcision. In the United States and Europe, where sexual
transmission among men who have sex with men (MSM) is dominant, circumcision
has not demonstrated substantial benefit. (See 'Male circumcision' above.)
Serodiscordant couples — The term "serodiscordant couples" refers to ongoing
sexual partnerships between an individual living with HIV and an uninfected
individual. Prevention strategies for individuals living with HIV and at-risk
individuals are thus relevant to each of the members of the serodiscordant couple,
respectively. (See 'Individuals living with HIV' above and 'Individuals at risk for
HIV' above.)
HIV transmission can be reduced with ART for the partner living with HIV [12,82]
and with pre-exposure prophylaxis for the uninfected partner [150]. For all
patients living with HIV in a serodiscordant partnership, we recommend initiation
of ART in order to prevent transmission to the uninfected partner (see 'Treatment
as prevention' above). No studies have directly compared the two strategies for
HIV prevention, but ART for the partner living with HIV has the additional benefit of
reducing the AIDS and non-AIDS morbidity and mortality for that individual [82].
Pre-exposure prophylaxis for the partner without HIV may be indicated until the
partner living with HIV has achieved stable viral suppression on ART (typically by
six months after initiating therapy [151,152]), if ART fails to suppress HIV in the
partner living with HIV for any reason, and for risk-taking behavior outside the
partnership. (See "Administration of pre-exposure prophylaxis against HIV
infection".)
Counseling on condom use and other risk reduction strategies is discussed
elsewhere. (See 'Counseling on condom use' above and 'Risk reduction' above.)
Options for serodiscordant couples desiring pregnancy are also discussed
elsewhere. (See "Use of assisted reproduction in HIV- and hepatitis-infected
couples", section on 'Natural conception in serodiscordant couples'.)
Pregnant and breastfeeding women — Prevention of mother-to-child
transmission of HIV involves ART for the pregnant woman and postexposure
prophylaxis for the infant. Precise management differs in resource-rich and limited
settings and is discussed elsewhere. (See "Antiretroviral selection and
management in pregnant women with HIV in resource-rich
settings" and "Prevention of mother-to-child HIV transmission in resource-limited
settings" and "Prevention of HIV transmission during breastfeeding in resourcelimited settings".)
A PUBLIC HEALTH PLAN FOR THE UNITED STATES
Utilizing the
prevention interventions described below, the United States has described a plan
to reduce incident HIV in the United States by 90 percent by 2030 [153]. The plan
has "4 pillars":
●Diagnose all individuals with HIV as early as possible after infection
●Treat HIV rapidly and successfully to achieve sustained viral
suppression
●Prevent
at-risk people from acquiring HIV through interventions
including the use of pre-exposure prophylaxis
●Rapidly detect and respond to emerging clusters of HIV infection to
further reduce new transmissions
This plan has a strong focus in the southern United States and some additional
urban centers where HIV spread continues [153].
SOCIETY GUIDELINE LINKS
Links to society and government-
sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: HIV prevention".)
SUMMARY AND RECOMMENDATIONS
●HIV
infection is acquired through sexual intercourse, exposure to
infected blood, or perinatal transmission. For all modes of
transmission, a higher viral load in the source individual living with
HIV is associated with a greater risk of transmission. (See 'Modes of
acquisition' above and 'Viremia in the source individual and acute
HIV' above.)
●The risk of sexual transmission of HIV varies widely depending on
the type of exposure. In general, exposures that lead to mucosal
disruption and bleeding are associated with higher risk than other
exposures. Unprotected anal sex conveys the greatest probability of
HIV transmission and oral sex the lowest. Lack of circumcision is
associated with HIV acquisition in men, and concurrent sexually
transmitted infections are associated with both transmission and
acquisition. Other behavioral factors, such as whether condoms were
used, the number of sexual partners, and sex under the influence of
recreational drugs, also affect overall sexual HIV transmission risk.
(See 'Sexual transmission risk factors' above.)
●The risk of parenteral transmission of HIV depends on the volume of
contaminated blood that an individual is exposed to and the depth of
the injury or exposure (eg, mucous membrane exposure, needle-stick,
or injection into vessel). (See 'Bloodborne transmission risk
factors' above.)
●A comprehensive approach to HIV prevention includes risk reduction
among individuals living with HIV to reduce transmission and among
at-risk individuals to reduce acquisition (see 'Clinical approach to HIV
prevention' above):
•For individuals living with HIV, successful antiretroviral therapy
(ART) is a key strategy to prevent transmission. The risk of
transmission from an individual living with HIV who has achieved
stable viral suppression is negligible. (See 'Individuals living with
HIV' above and 'Treatment as prevention' above.)
•For at-risk individuals, routine screening and having a low
threshold to test for HIV in order to identify new HIV infections is
crucial to directing interventions to prevent transmission. Condom
use and risk-reduction counseling as well as harm reduction
interventions can reduce behavior that results in higher risk of
infection. Once infection is excluded, antiretroviral-based
strategies that can reduce the risk of HIV acquisition include daily
pre-exposure prophylaxis for individuals with high ongoing risk,
and postexposure prophylaxis for those who have had a mucosal
or parenteral exposure to HIV within the prior 72 hours.
(See 'Individuals at risk for HIV' above and "Screening and
diagnostic testing for HIV infection" and "Administration of preexposure prophylaxis against HIV infection" and "Management of
nonoccupational exposures to HIV and hepatitis B and C in
adults".)
•For serodiscordant couples, we recommend antiretroviral
treatment of the partner living with HIV as the primary prevention
strategy instead of antiretroviral prophylaxis for the uninfected
partner (Grade 1A). Pre-exposure prophylaxis for the partner
without HIV is additionally indicated until the infected partner has
achieved stable viral suppression on ART (typically by six months
after initiating therapy), if ART fails to suppress HIV in the partner
living with HIV for any reason or for risk-taking behavior outside
the partnership. Management of serodiscordant couples desiring
pregnancy is discussed elsewhere. (See 'Serodiscordant
couples' above and "Use of assisted reproduction in HIV- and
hepatitis-infected couples", section on 'Natural conception in
serodiscordant couples'.)
•Behavioral interventions (such as condom use and risk-reduction
counseling) remain crucial elements of prevention. For individuals
living with HIV who have achieved viral suppression and their
sexual partners, the risk of HIV transmission is negligible.
However, continued condom use remains useful to reduce risk of
other STIs and in case viral suppression fails. (See 'Condom
use' above and 'Counseling and harm reduction strategies' above
and 'Serodiscordant couples' above.)
•We screen for and treat sexually transmitted infections in all
individuals with or at risk for HIV infection given the shared risk
factors for HIV and other STIs, the association of other STIs with
HIV infection, and the benefit of treating STIs beyond potential HIV
prevention. (See 'Treatment of sexually transmitted
infections' above.)
•Circumcision has demonstrated efficacy in reducing the risk of
HIV acquisition among heterosexual men, but the benefit among
men who have sex with men (MSM) is uncertain. In areas where
the prevalence of HIV is high and sexual transmission is mainly
among heterosexuals, such as in several African countries,
voluntary medical circumcision can be an effective element of HIV
prevention intervention. (See 'Male circumcision' above.)
ACKNOWLEDGMENT
We are saddened by the death of John G Bartlett,
MD, who passed away in January 2021. UpToDate gratefully acknowledges Dr.
Bartlett's role as section editor on this topic, his tenure as the founding Editor-inChief for UpToDate in Infectious Diseases, and his dedicated and longstanding
involvement with the UpToDate program.
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Centers for Disease Control and Prevention. HIV Surveillance Report.
https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html (Acces
sed on August 08, 2018).
2. Hess KL, Hu X, Lansky A, et al. Lifetime risk of a diagnosis of HIV
infection in the United States. Ann Epidemiol 2017; 27:238.
3. Centers for Disease Control and Prevention. CDC Fact Sheet HIV amo
ng gay and bisexual men. https://www.cdc.gov/nchhstp/newsroom/
docs/factsheets/cdc-msm-508.pdf (Accessed on November 18, 2019).
4. 2020 Global AIDS Update ⁠— Seizing the moment ⁠— Tackling entrenc
hed inequalities to end epidemics https://www.unaids.org/en/resour
ces/documents/2020/global-aids-report (Accessed on December 09,
2020).
5. Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the
heterosexual infectivity of HIV-1: a systematic review and metaanalysis. Lancet Infect Dis 2008; 8:553.
6. Boily MC, Baggaley RF, Wang L, et al. Heterosexual risk of HIV-1
infection per sexual act: systematic review and meta-analysis of
observational studies. Lancet Infect Dis 2009; 9:118.
7. Baggaley RF, Boily MC, White RG, Alary M. Risk of HIV-1 transmission
for parenteral exposure and blood transfusion: a systematic review
and meta-analysis. AIDS 2006; 20:805.
8. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and
heterosexual transmission of human immunodeficiency virus type 1.
Rakai Project Study Group. N Engl J Med 2000; 342:921.
9. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1
transmission per coital act in monogamous, heterosexual, HIV-1discordant couples in Rakai, Uganda. Lancet 2001; 357:1149.
10. Dorak MT, Tang J, Penman-Aguilar A, et al. Transmission of HIV-1 and
HLA-B allele-sharing within serodiscordant heterosexual Zambian
couples. Lancet 2004; 363:2137.
11. Attia S, Egger M, Müller M, et al. Sexual transmission of HIV
according to viral load and antiretroviral therapy: systematic review
and meta-analysis. AIDS 2009; 23:1397.
12. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral Therapy for the
Prevention of HIV-1 Transmission. N Engl J Med 2016; 375:830.
13. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission
after initiation of antiretroviral therapy: a prospective cohort
analysis. Lancet 2010; 375:2092.
14. Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without
Condoms and Risk of HIV Transmission in Serodifferent Couples
When the HIV-Positive Partner Is Using Suppressive Antiretroviral
Therapy. JAMA 2016; 316:171.
15. Bavinton BR, Pinto AN, Phanuphak N, et al. Viral suppression and HIV
transmission in serodiscordant male couples: an international,
prospective, observational, cohort study. Lancet HIV 2018; 5:e438.
16. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission
through condomless sex in serodifferent gay couples with the HIVpositive partner taking suppressive antiretroviral therapy (PARTNER):
final results of a multicentre, prospective, observational study.
Lancet 2019; 393:2428.
17. The Lancet Hiv . U=U taking off in 2017. Lancet HIV 2017; 4:e475.
18. Cohen MS. Successful treatment of HIV eliminates sexual
transmission. Lancet 2019; 393:2366.
19. Liebenberg LJ, Masson L, Arnold KB, et al. Genital-Systemic
Chemokine Gradients and the Risk of HIV Acquisition in Women. J
Acquir Immune Defic Syndr 2017; 74:318.
20. Baeten JM, Kahle E, Lingappa JR, et al. Genital HIV-1 RNA predicts risk
of heterosexual HIV-1 transmission. Sci Transl Med 2011; 3:77ra29.
21. Blaser N, Wettstein C, Estill J, et al. Impact of viral load and the
duration of primary infection on HIV transmission: systematic review
and meta-analysis. AIDS 2014; 28:1021.
22. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1
transmission per coital act, by stage of HIV-1 infection, in Rakai,
Uganda. J Infect Dis 2005; 191:1403.
23. Pilcher CD, Joaki G, Hoffman IF, et al. Amplified transmission of HIV1: comparison of HIV-1 concentrations in semen and blood during
acute and chronic infection. AIDS 2007; 21:1723.
24. Powers KA, Ghani AC, Miller WC, et al. The role of acute and early HIV
infection in the spread of HIV and implications for transmission
prevention strategies in Lilongwe, Malawi: a modelling study. Lancet
2011; 378:256.
25. Pao D, Fisher M, Hué S, et al. Transmission of HIV-1 during primary
infection: relationship to sexual risk and sexually transmitted
infections. AIDS 2005; 19:85.
26. Volz EM, Ionides E, Romero-Severson EO, et al. HIV-1 transmission
during early infection in men who have sex with men: a
phylodynamic analysis. PLoS Med 2013; 10:e1001568; discussion
e1001568.
27. Hollingsworth TD, Pilcher CD, Hecht FM, et al. High Transmissibility
During Early HIV Infection Among Men Who Have Sex With Men-San
Francisco, California. J Infect Dis 2015; 211:1757.
28. Marzel A, Shilaih M, Yang WL, et al. HIV-1 Transmission During
Recent Infection and During Treatment Interruptions as Major
Drivers of New Infections in the Swiss HIV Cohort Study. Clin Infect
Dis 2016; 62:115.
29. Ma ZM, Stone M, Piatak M Jr, et al. High specific infectivity of plasma
virus from the pre-ramp-up and ramp-up stages of acute simian
immunodeficiency virus infection. J Virol 2009; 83:3288.
30. Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in
semen despite effective antiretroviral therapy. AIDS 2009; 23:2050.
31. Lambert-Niclot S, Tubiana R, Beaudoux C, et al. Detection of HIV-1
RNA in seminal plasma samples from treated patients with
undetectable HIV-1 RNA in blood plasma on a 2002-2011 survey. AIDS
2012; 26:971.
32. Pasquier C, Sauné K, Raymond S, et al. Determining seminal plasma
human immunodeficiency virus type 1 load in the context of efficient
highly active antiretroviral therapy. J Clin Microbiol 2009; 47:2883.
33. Politch JA, Mayer KH, Welles SL, et al. Highly active antiretroviral
therapy does not completely suppress HIV in semen of sexually
active HIV-infected men who have sex with men. AIDS 2012; 26:1535.
34. Ghosn J, Leruez-Ville M, Blanche J, et al. HIV-1 DNA levels in
peripheral blood mononuclear cells and cannabis use are associated
with intermittent HIV shedding in semen of men who have sex with
men on successful antiretroviral regimens. Clin Infect Dis 2014;
58:1763.
35. Cu-Uvin S, Caliendo AM, Reinert S, et al. Effect of highly active
antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS 2000;
14:415.
36. Neely MN, Benning L, Xu J, et al. Cervical shedding of HIV-1 RNA
among women with low levels of viremia while receiving highly
active antiretroviral therapy. J Acquir Immune Defic Syndr 2007;
44:38.
37. McQuillan GM, Kruszon-Moran D, Granade T, Feldman JW.
Seroprevalence of HIV in the US Household Population Aged 18–49
Years: The National Health and Nutrition Examination Surveys, 1999–
2006. J Acquir Immune Defic Syndr 2010; 53:117.
38. Baggaley RF, White RG, Boily MC. HIV transmission risk through anal
intercourse: systematic review, meta-analysis and implications for
HIV prevention. Int J Epidemiol 2010; 39:1048.
39. Katz MH, Gerberding JL. Postexposure treatment of people exposed
to the human immunodeficiency virus through sexual contact or
injection-drug use. N Engl J Med 1997; 336:1097.
40. Vittinghoff E, Douglas J, Judson F, et al. Per-contact risk of human
immunodeficiency virus transmission between male sexual partners.
Am J Epidemiol 1999; 150:306.
41. Kaplan EH, Heimer R. A model-based estimate of HIV infectivity via
needle sharing. J Acquir Immune Defic Syndr 1992; 5:1116.
42. Rozenbaum W, Gharakhanian S, Cardon B, et al. HIV transmission by
oral sex. Lancet 1988; 1:1395.
43. Lazzarin A, Saracco A, Musicco M, Nicolosi A. Man-to-woman sexual
transmission of the human immunodeficiency virus. Risk factors
related to sexual behavior, man's infectiousness, and woman's
susceptibility. Italian Study Group on HIV Heterosexual Transmission.
Arch Intern Med 1991; 151:2411.
44. Seidlin M, Vogler M, Lee E, et al. Heterosexual transmission of HIV in
a cohort of couples in New York City. AIDS 1993; 7:1247.
45. Buchbinder SP, Vittinghoff E, Heagerty PJ, et al. Sexual risk, nitrite
inhalant use, and lack of circumcision associated with HIV
seroconversion in men who have sex with men in the United States. J
Acquir Immune Defic Syndr 2005; 39:82.
46. de Oliveira T, Kharsany AB, Gräf T, et al. Transmission networks and
risk of HIV infection in KwaZulu-Natal, South Africa: a communitywide phylogenetic study. Lancet HIV 2017; 4:e41.
47. Patel P, Borkowf CB, Brooks JT, et al. Estimating per-act HIV
transmission risk: a systematic review. AIDS 2014; 28:1509.
48. Leynaert B, Downs AM, de Vincenzi I. Heterosexual transmission of
human immunodeficiency virus: variability of infectivity throughout
the course of infection. European Study Group on Heterosexual
Transmission of HIV. Am J Epidemiol 1998; 148:88.
49. Comparison of female to male and male to female transmission of
HIV in 563 stable couples. European Study Group on Heterosexual
Transmission of HIV. BMJ 1992; 304:809.
50. Chan SK, Thornton LR, Chronister KJ, et al. Likely female-to-female
sexual transmission of HIV--Texas, 2012. MMWR Morb Mortal Wkly
Rep 2014; 63:209.
51. Kwakwa HA, Ghobrial MW. Female-to-female transmission of human
immunodeficiency virus. Clin Infect Dis 2003; 36:e40.
52. Donoval BA, Landay AL, Moses S, et al. HIV-1 target cells in foreskins
of African men with varying histories of sexually transmitted
infections. Am J Clin Pathol 2006; 125:386.
53. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled
intervention trial of male circumcision for reduction of HIV infection
risk: the ANRS 1265 Trial. PLoS Med 2005; 2:e298.
54. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV
prevention in young men in Kisumu, Kenya: a randomised controlled
trial. Lancet 2007; 369:643.
55. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV
prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007;
369:657.
56. Gray R, Kigozi G, Kong X, et al. The effectiveness of male circumcision
for HIV prevention and effects on risk behaviors in a posttrial followup study. AIDS 2012; 26:609.
57. Fleming DT, Wasserheit JN. From epidemiological synergy to public
health policy and practice: the contribution of other sexually
transmitted diseases to sexual transmission of HIV infection. Sex
Transm Infect 1999; 75:3.
58. Cohen CR, Lingappa JR, Baeten JM, et al. Bacterial vaginosis
associated with increased risk of female-to-male HIV-1 transmission:
a prospective cohort analysis among African couples. PLoS Med
2012; 9:e1001251.
59. Myer L, Denny L, Telerant R, et al. Bacterial vaginosis and
susceptibility to HIV infection in South African women: A nested casecontrol study. J Infect Dis 2005; 192:1372.
60. Masson L, Barnabas S, Deese J, et al. Inflammatory cytokine
biomarkers of asymptomatic sexually transmitted infections and
vaginal dysbiosis: a multicentre validation study. Sex Transm Infect
2019; 95:5.
61. Klatt NR, Cheu R, Birse K, et al. Vaginal bacteria modify HIV tenofovir
microbicide efficacy in African women. Science 2017; 356:938.
62. Freeman EE, Weiss HA, Glynn JR, et al. Herpes simplex virus 2
infection increases HIV acquisition in men and women: systematic
review and meta-analysis of longitudinal studies. AIDS 2006; 20:73.
63. Reynolds SJ, Risbud AR, Shepherd ME, et al. High rates of syphilis
among STI patients are contributing to the spread of HIV-1 in India.
Sex Transm Infect 2006; 82:121.
64. Mlisana K, Naicker N, Werner L, et al. Symptomatic vaginal discharge
is a poor predictor of sexually transmitted infections and genital tract
inflammation in high-risk women in South Africa. J Infect Dis 2012;
206:6.
65. Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus
viral load in blood plasma and semen: review and implications of
empirical findings. Sex Transm Dis 2008; 35:55.
66. Sadiq ST, Taylor S, Kaye S, et al. The effects of antiretroviral therapy
on HIV-1 RNA loads in seminal plasma in HIV-positive patients with
and without urethritis. AIDS 2002; 16:219.
67. Chen JS, Matoga M, Massa C, et al. Effects of Urethritis on Human
Immunodeficiency Virus (HIV) in Semen: Implications for HIV
Prevention and Cure. Clin Infect Dis 2021; 73:e2000.
68. Simmons G, Wilkinson D, Reeves JD, et al. Primary, syncytiuminducing human immunodeficiency virus type 1 isolates are dualtropic and most can use either Lestr or CCR5 as coreceptors for virus
entry. J Virol 1996; 70:8355.
69. Gupta RK, Abdul-Jawad S, McCoy LE, et al. HIV-1 remission following
CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 2019;
568:244.
70. Bauer G, Anderson JS. Stem cell transplantation in the context of HIV-how can we cure HIV infection? Expert Rev Clin Immunol 2014;
10:107.
71. Hütter G, Nowak D, Mossner M, et al. Long-term control of HIV by
CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009;
360:692.
72. Thomson KA, Hughes J, Baeten JM, et al. Increased Risk of HIV
Acquisition Among Women Throughout Pregnancy and During the
Postpartum Period: A Prospective Per-Coital-Act Analysis Among
Women With HIV-Infected Partners. J Infect Dis 2018; 218:16.
73. Drake AL, Wagner A, Richardson B, John-Stewart G. Incident HIV
during pregnancy and postpartum and risk of mother-to-child HIV
transmission: a systematic review and meta-analysis. PLoS Med 2014;
11:e1001608.
74. Masson L, Passmore JA, Liebenberg LJ, et al. Genital inflammation
and the risk of HIV acquisition in women. Clin Infect Dis 2015; 61:260.
75. Selhorst P, Masson L, Ismail SD, et al. Cervicovaginal Inflammation
Facilitates Acquisition of Less Infectious HIV Variants. Clin Infect Dis
2017; 64:79.
76. Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure
prophylaxis after sexual, injection-drug use, or other
nonoccupational exposure to HIV in the United States:
recommendations from the U.S. Department of Health and Human
Services. MMWR Recomm Rep 2005; 54:1.
77. Kaplan EH, Heimer R. HIV incidence among New Haven needle
exchange participants: updated estimates from syringe tracking and
testing data. J Acquir Immune Defic Syndr Hum Retrovirol 1995;
10:175.
78. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV
seroconversion in health care workers after percutaneous exposure.
Centers for Disease Control and Prevention Needlestick Surveillance
Group. N Engl J Med 1997; 337:1485.
79. Joyce MP, Kuhar D, Brooks JT. Notes from the field: occupationally
acquired HIV infection among health care workers - United States,
1985-2013. MMWR Morb Mortal Wkly Rep 2015; 63:1245.
80. Spiller MW, Broz D, Wejnert C, et al. HIV infection and HIV-associated
behaviors among persons who inject drugs--20 cities, United States,
2012. MMWR Morb Mortal Wkly Rep 2015; 64:270.
81. LeMessurier J, Traversy G, Varsaneux O, et al. Risk of sexual
transmission of human immunodeficiency virus with antiretroviral
therapy, suppressed viral load and condom use: a systematic review.
CMAJ 2018; 190:E1350.
82. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection
with early antiretroviral therapy. N Engl J Med 2011; 365:493.
83. Muessig KE, Cohen MS. Advances in HIV prevention for
serodiscordant couples. Curr HIV/AIDS Rep 2014; 11:434.
84. Bunnell R, Ekwaru JP, Solberg P, et al. Changes in sexual behavior
and risk of HIV transmission after antiretroviral therapy and
prevention interventions in rural Uganda. AIDS 2006; 20:85.
85. Jia Z, Mao Y, Zhang F, et al. Antiretroviral therapy to prevent HIV
transmission in serodiscordant couples in China (2003-11): a national
observational cohort study. Lancet 2013; 382:1195.
86. Supervie V, Viard JP, Costagliola D, Breban R. Heterosexual risk of HIV
transmission per sexual act under combined antiretroviral therapy:
systematic review and bayesian modeling. Clin Infect Dis 2014;
59:115.
87. Jean K, Gabillard D, Moh R, et al. Effect of early antiretroviral therapy
on sexual behaviors and HIV-1 transmission risk among adults with
diverse heterosexual partnership statuses in Côte d'Ivoire. J Infect
Dis 2014; 209:431.
88. Anglemyer A, Rutherford GW, Egger M, Siegfried N. Antiretroviral
therapy for prevention of HIV transmission in HIV-discordant
couples. Cochrane Database Syst Rev 2011; :CD009153.
89. Smith MK, Westreich D, Liu H, et al. Treatment to Prevent HIV
Transmission in Serodiscordant Couples in Henan, China, 2006 to
2012. Clin Infect Dis 2015; 61:111.
90. Oldenburg CE, Bärnighausen T, Tanser F, et al. Antiretroviral Therapy
to Prevent HIV Acquisition in Serodiscordant Couples in a
Hyperendemic Community in Rural South Africa. Clin Infect Dis 2016;
63:548.
91. Grabowski MK, Serwadda DM, Gray RH, et al. HIV Prevention Efforts
and Incidence of HIV in Uganda. N Engl J Med 2017; 377:2154.
92. Tanser F, Bärnighausen T, Grapsa E, et al. High coverage of ART
associated with decline in risk of HIV acquisition in rural KwaZuluNatal, South Africa. Science 2013; 339:966.
93. Smith MK, Powers KA, Muessig KE, et al. HIV treatment as
prevention: the utility and limitations of ecological observation. PLoS
Med 2012; 9:e1001260.
94. Miller WC, Hoffman IF, Hanscom BS, et al. A scalable, integrated
intervention to engage people who inject drugs in HIV care and
medication-assisted treatment (HPTN 074): a randomised, controlled
phase 3 feasibility and efficacy study. Lancet 2018; 392:747.
95. Granich RM, Gilks CF, Dye C, et al. Universal voluntary HIV testing
with immediate antiretroviral therapy as a strategy for elimination of
HIV transmission: a mathematical model. Lancet 2009; 373:48.
96. Abbas UL. Uptake of biomedical interventions for prevention of
sexually transmitted HIV. Curr Opin HIV AIDS 2011; 6:114.
97. Palombi L, Bernava GM, Nucita A, et al. Predicting trends in HIV-1
sexual transmission in sub-Saharan Africa through the Drug
Resource Enhancement Against AIDS and Malnutrition model:
antiretrovirals for 5 reduction of population infectivity, incidence and
prevalence at the district level. Clin Infect Dis 2012; 55:268.
98. Iwuji CC, Orne-Gliemann J, Larmarange J, et al. Universal test and
treat and the HIV epidemic in rural South Africa: a phase 4, openlabel, community cluster randomised trial. Lancet HIV 2018; 5:e116.
99. Makhema J, Wirth KE, Pretorius Holme M, et al. Universal Testing,
Expanded Treatment, and Incidence of HIV Infection in Botswana. N
Engl J Med 2019; 381:230.
100.
Havlir DV, Balzer LB, Charlebois ED, et al. HIV Testing and
Treatment with the Use of a Community Health Approach in Rural
Africa. N Engl J Med 2019; 381:219.
101.
Hayes RJ, Donnell D, Floyd S, et al. Effect of Universal Testing
and Treatment on HIV Incidence - HPTN 071 (PopART). N Engl J Med
2019; 381:207.
102.
Justman JE, Mugurungi O, El-Sadr WM. HIV Population Surveys Bringing Precision to the Global Response. N Engl J Med 2018;
378:1859.
103.
Davis KR, Weller SC. The effectiveness of condoms in reducing
heterosexual transmission of HIV. Fam Plann Perspect 1999; 31:272.
104.
Holmes KK, Levine R, Weaver M. Effectiveness of condoms in
preventing sexually transmitted infections. Bull World Health Organ
2004; 82:454.
105.
Weller S, Davis K. Condom effectiveness in reducing
heterosexual HIV transmission. Cochrane Database Syst Rev 2002;
:CD003255.
106.
Lubinski C, Aberg J, Bardeguez AD, et al. HIV policy: the path
forward--a joint position paper of the HIV Medicine Association of
the Infectious Diseases Society of America and the American College
of Physicians. Clin Infect Dis 2009; 48:1335.
107.
Pinkerton SD, Abramson PR. Effectiveness of condoms in
preventing HIV transmission. Soc Sci Med 1997; 44:1303.
108.
Van de Perre P, Jacobs D, Sprecher-Goldberger S. The latex
condom, an efficient barrier against sexual transmission of AIDSrelated viruses. AIDS 1987; 1:49.
109.
Drew WL, Blair M, Miner RC, Conant M. Evaluation of the virus
permeability of a new condom for women. Sex Transm Dis 1990;
17:110.
110.
Grund JM, Toledo C, Davis SM, et al. Notes from the Field:
Tetanus Cases After Voluntary Medical Male Circumcision for HIV
Prevention--Eastern and Southern Africa, 2012-2015. MMWR Morb
Mortal Wkly Rep 2016; 65:36.
111.
WHO Informal consultation on tetanus and voluntary medical
male circumcision, Technical consultation update to the WHO March
2015 meeting report. June 2016. http://www.who.int/hiv/pub/malecir
cumcision/male-circumcision-2016-update/en/ (Accessed on May 02,
2017).
112.
Auvert B, Taljaard D, Rech D, et al. Association of the ANRS12126 male circumcision project with HIV levels among men in a
South African township: evaluation of effectiveness using crosssectional surveys. PLoS Med 2013; 10:e1001509.
113.
Kigozi G, Musoke R, Kighoma N, et al. Safety of medical male
circumcision in human immunodeficiency virus-infected men in
Rakai, Uganda. Urology 2014; 83:294.
114.
Kong X, Kigozi G, Ssekasanvu J, et al. Association of Medical
Male Circumcision and Antiretroviral Therapy Scale-up With
Community HIV Incidence in Rakai, Uganda. JAMA 2016; 316:182.
115.
Warner L, Ghanem KG, Newman DR, et al. Male circumcision
and risk of HIV infection among heterosexual African American men
attending Baltimore sexually transmitted disease clinics. J Infect Dis
2009; 199:59.
116.
Sawires SR, Dworkin SL, Fiamma A, et al. Male circumcision and
HIV/AIDS: challenges and opportunities. Lancet 2007; 369:708.
117.
Agot KE, Kiarie JN, Nguyen HQ, et al. Male circumcision in Siaya
and Bondo Districts, Kenya: prospective cohort study to assess
behavioral disinhibition following circumcision. J Acquir Immune
Defic Syndr 2007; 44:66.
118.
Kong X, Kigozi G, Nalugoda F, et al. Assessment of changes in
risk behaviors during 3 years of posttrial follow-up of male
circumcision trial participants uncircumcised at trial closure in Rakai,
Uganda. Am J Epidemiol 2012; 176:875.
119.
Wawer MJ, Makumbi F, Kigozi G, et al. Circumcision in HIVinfected men and its effect on HIV transmission to female partners in
Rakai, Uganda: a randomised controlled trial. Lancet 2009; 374:229.
120.
Millett GA, Flores SA, Marks G, et al. Circumcision status and risk
of HIV and sexually transmitted infections among men who have sex
with men: a meta-analysis. JAMA 2008; 300:1674.
121.
Centers for Disease Control and Prevention. Effective interventi
ons: HIV prevention that works. https://effectiveinterventions.cdc.go
v/en/HighImpactPrevention/Interventions.aspx (Accessed on June 16
, 2015).
122.
Workowski KA, Bachmann LH, Chan PA, et al. Sexually
Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm
Rep 2021; 70:1.
123.
Scott-Sheldon LA, Huedo-Medina TB, Warren MR, et al. Efficacy
of behavioral interventions to increase condom use and reduce
sexually transmitted infections: a meta-analysis, 1991 to 2010. J
Acquir Immune Defic Syndr 2011; 58:489.
124.
Eaton LA, Huedo-Medina TB, Kalichman SC, et al. Meta-analysis
of single-session behavioral interventions to prevent sexually
transmitted infections: implications for bundling prevention
packages. Am J Public Health 2012; 102:e34.
125.
Gowing L, Farrell MF, Bornemann R, et al. Oral substitution
treatment of injecting opioid users for prevention of HIV infection.
Cochrane Database Syst Rev 2011; :CD004145.
126.
Stoltz JA, Wood E, Small W, et al. Changes in injecting practices
associated with the use of a medically supervised safer injection
facility. J Public Health (Oxf) 2007; 29:35.
127.
Strathdee SA, Hallett TB, Bobrova N, et al. HIV and risk
environment for injecting drug users: the past, present, and future.
Lancet 2010; 376:268.
128.
Neaigus A, Zhao M, Gyarmathy VA, et al. Greater drug injecting
risk for HIV, HBV, and HCV infection in a city where syringe exchange
and pharmacy syringe distribution are illegal. J Urban Health 2008;
85:309.
129.
Altice FL, Bruce RD, Lucas GM, et al. HIV treatment outcomes
among HIV-infected, opioid-dependent patients receiving
buprenorphine/naloxone treatment within HIV clinical care settings:
results from a multisite study. J Acquir Immune Defic Syndr 2011; 56
Suppl 1:S22.
130.
Stillwaggon E, Sawers L. Rush to judgment: the STI-treatment
trials and HIV in sub-Saharan Africa. J Int AIDS Soc 2015; 18:19844.
131.
Padian NS, McCoy SI, Balkus JE, Wasserheit JN. Weighing the
gold in the gold standard: challenges in HIV prevention research.
AIDS 2010; 24:621.
132.
Kaul R, Kimani J, Nagelkerke NJ, et al. Monthly antibiotic
chemoprophylaxis and incidence of sexually transmitted infections
and HIV-1 infection in Kenyan sex workers: a randomized controlled
trial. JAMA 2004; 291:2555.
133.
Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized,
double-blind, placebo-controlled efficacy trial of a bivalent
recombinant glycoprotein 120 HIV-1 vaccine among injection drug
users in Bangkok, Thailand. J Infect Dis 2006; 194:1661.
134.
Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase
3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1
infection. J Infect Dis 2005; 191:654.
135.
Gray GE, Bekker LG, Laher F, et al. Vaccine Efficacy of ALVAC-HIV
and Bivalent Subtype C gp120-MF59 in Adults. N Engl J Med 2021;
384:1089.
136.
Haynes BF, Gilbert PB, McElrath MJ, et al. Immune-correlates
analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 2012;
366:1275.
137.
Barouch DH, Deeks SG. Immunologic strategies for HIV-1
remission and eradication. Science 2014; 345:169.
138.
Burton DR, Mascola JR. Antibody responses to envelope
glycoproteins in HIV-1 infection. Nat Immunol 2015; 16:571.
139.
Burton DR, Ahmed R, Barouch DH, et al. A Blueprint for HIV
Vaccine Discovery. Cell Host Microbe 2012; 12:396.
140.
Caskey M, Klein F, Lorenzi JC, et al. Viraemia suppressed in HIV1-infected humans by broadly neutralizing antibody 3BNC117.
Nature 2015; 522:487.
141.
Corey L, Gilbert PB, Juraska M, et al. Two Randomized Trials of
Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med
2021; 384:1003.
142.
United States Department of Health and Human Services. Guid
elines for the Use of Antiretroviral Agents in Adults and Adolescents
Living with HIV. https://clinicalinfo.hiv.gov/en/guidelines/adult-andadolescent-arv/whats-new-guidelines (Accessed on November 23, 20
20).
143.
https://www.who.int/publications/guidelines/hiv_aids/en/ (Acc
essed on December 09, 2020).
144.
Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral Drugs for
Treatment and Prevention of HIV Infection in Adults: 2020
Recommendations of the International Antiviral Society-USA Panel.
JAMA 2020; 324:1651.
145.
TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al. A
Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in
Africa. N Engl J Med 2015; 373:808.
146.
INSIGHT START Study Group, Lundgren JD, Babiker AG, et al.
Initiation of Antiretroviral Therapy in Early Asymptomatic HIV
Infection. N Engl J Med 2015; 373:795.
147.
World Health Organization. Consolidated guidelines on the use
of antiretroviral drugs for treating and preventing HIV infection, seco
nd edition. June 2016. http://www.who.int/hiv/pub/arv/arv-2016/en/
(Accessed on June 15, 2016).
148.
Eshleman SH, Hudelson SE, Redd AD, et al. Treatment as
Prevention: Characterization of Partner Infections in the HIV
Prevention Trials Network 052 Trial. J Acquir Immune Defic Syndr
2017; 74:112.
149.
Kalichman SC, Pellowski J, Turner C. Prevalence of sexually
transmitted co-infections in people living with HIV/AIDS: systematic
review with implications for using HIV treatments for prevention. Sex
Transm Infect 2011; 87:183.
150.
Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis
for HIV prevention in heterosexual men and women. N Engl J Med
2012; 367:399.
151.
Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus
abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J
Med 2013; 369:1807.
152.
Mills AM, Nelson M, Jayaweera D, et al. Once-daily
darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1infected patients: 96-week analysis. AIDS 2009; 23:1679.
153.
Fauci AS, Redfield RR, Sigounas G, et al. Ending the HIV
Epidemic: A Plan for the United States. JAMA 2019; 321:844.
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