3475
Contact address: am_barrios@hotmail.com
SAFETY AND EFFICACY OF COMBINATIONS BASED ON
DIDANOSINE 400 mg OD PLUS TENOFOVIR 300 mg OD
Ana Barrios1, Ivana Maida1, Leticia Pérez-Saleme1, Eugenia Negredo2, Bonaventura Clotet2, Julia Vilaró-Rodríguez3, Pere
Domingo3, Mª José Galindo3, Vicente Estrada4, Jesús Santos5, Víctor Asensi6, Pablo Labarga7, José Alberto Terrón8,
Antonio Vergara9, Teresa García-Benayas1, Luz Martín-Carbonero1, Pablo Barreiro1, Francisco Blanco1, Juan GonzálezLahoz1, and Vincent Soriano1
1
Service of Infectious Diseases, Hospital Carlos III, Madrid; 2Hospital Germans Trias i Pujol, Barcelona; 3Infectious Diseases
Unit, Hospital de Sant Pau, Barcelona; 4Hospital Clínico San Carlos, Madrid; 5Hospital Virgen de la Victoria, Málaga;
6
Hospital Central de Asturias, Oviedo; 7Hospital de San Millán, Logroño; 8Hospital de Jerez, Cádiz; 9Hospital de Puerto Real,
Cádiz, Spain
BACKGROUND
The use of antiretroviral regimens based on
didanosine (ddI) plus tenofovir disoproxil fumarate (TDF)
have attracted much concern due to their
pharmacokinetic
interactions.
As
ddI
plasma
concentrations increased (up to 60%) when
coadministered with TDF, ddI-related toxicity might
appear more frequently.
At 3 months of follow-up, overall virologic
response (HIV-RNA < 400 copies/ml) was recorded in
75% of patients (OT analysis), and the median increase
in the CD4 count was of 19 cells/l. At 6 months,
virologic response was achieved in 75% of subjects, and
the median variation in the CD4 count was of + 29
cells/l. Table 1 records virologic and immunologic
responses as a function of the situation in which
antiretroviral treatment was prescribed and the
concomitant drug-class administered with ddI and TDF.
Of note, patients on simplification regimens including ddI
and TDF plus NRTI showed a trend towards CD4 cell
decline (p=0.08) at 6 months (-251 cells/l on average),
which was not seen when using PI or NNRTI (+21 and
+49 cells/l, respectively).
Treatment discontinuation due to side
effects occurred in 16 patients: 8 EFV-related CNS
abnormalities, 1 EFV-related rash, 1 NVP-related
hepatotoxicity, 1 ddI-related neuropathy, 1 LPV/rtvrelated dyslipemia, and 4 gastrointestinal toxicity in the
absence of pancreatitis or hyperamylasemia. No kidney
disfunction were seen.
METHODS
In order to assess the safety and efficacy of
antiretroviral combinations based on ddI and TDF,
subjects from 9 Spanish hospitals who initiated regimens
including TDF 300 mg/ddI 400 mg od (250 mg if weight <
60 Kg) and with at least 3 months follow-up were
evaluated.
RESULTS
Data from 138 patients at 3 months and from
65 at 6 months were assessed. Their mean age was 41
years-old and 76% were male. They had acquired HIV
infection by intravenous drug use (45%), homosexual
contacts (34%), and heterosexual relationships (20%).
Up to 47% of subjects were C hepatitis virus coinfected.
Their mean time on antiretroviral therapy before
beginning ddI+TDF based regimen was 69 months. At
baseline, the mean plasma HIV-RNA was 4.25 log10 and
the mean CD4 count was 507 cells/l. Treatment was
prescribed in 3 situations: naïve, simplification, and
salvage therapy.
CONCLUSIONS
In summary, the combination of ddI plus TDF
at full doses does not seem to enhance the risk of toxicity
associated with ddI, at least during the first 6 months of
therapy. A poor correlation between plasma and
intracellular ddI levels may explain this finding.
Table 1. Virologic and immunologic responses (OT analyses) to ddI+TDF regimens at 3 and 6 months as a function of
prescription situation and concomitant drug-class.
At 3 months
(N = 138)
At 6 months
(N = 65)
Variables
Prescription
situation
Concomitant
drug-class
Naïve
Simplification
Rescue
PI
NNRTI
NRTI
N
Plasma
HIV-RNA
< 400 cop/ml
(% of patients)
CD4 count,
Δ median
(cells/l)
N
Plasma
HIV-RNA
< 400 cop/ml
(% of patients)
CD4 count,
Δ median
(cells/l)
14
82
42
33
80
25
79%
87%
51%
70%
88%
42%
+ 104 *
+4
+ 17
+ 48 *
+ 23
+ 12
5
25
35
25
19
21
80%
87%
66%
72%
94%
62%
+8
0
+ 45
+ 52
+ 49
- 36
OT: on treatment. Δ: variation. PI: protease inhibitors. NNRTI: no nucleoside analogs reverse trasncriptase inhibitors. NRTI: nucleoside analogs reverse trasncriptase
inhibitors.
* Statistically significant (p < 0.05).