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Background: The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale randomized trials among sub-Saharan African patients., Methods: This was a randomized open-label 96-week prospective pilot study evaluating four first-line regimens: tenofovir/emtricitabine/nevirapine (group 1), tenofovir/lopinavir/ritonavir (group 2), tenofovir/emtricitabine/zidovudine (group 3) and tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1-infected patients in Senegal and Cameroon. The primary end point was defined as an HIV-1 RNA viral load <50 copies/ml (study detection limit) at week 16 in ≥50% of patients using intention-to-treat analysis., Results: At baseline, 119 patients included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and median CD4(+) T-cell count of 200 cells/mm(3) (range 53-358). The primary end point was achieved for groups 1, 3 and 4 (58% [n=31], 62% [n=29] and 53% [n=30], respectively), but not for group 2 (38% [n=29]). At week 96, undetectable HIV-1 RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group 3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml (adjusted OR 5.56, 95% CI 1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged in three patients, all of whom were in group 2. Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event., Conclusions: Three efficient and safe tenofovir-based triple regimens were identified; the two-drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined virological threshold of efficacy.

The use of ritonavir as a protease inhibitor boost is rare in sub-Saharan Africa because a heat-stable formula is not available. We report the results of an open-label pilot trial with unboosted atazanavir in combination with lamivudine and didanosine as first-line therapy conducted in Senegal. Treatment-naive HIV-1 infected adult patients without active opportunistic disease were included. The primary endpoint was the proportion of patients with plasma HIV-1 RNA <400 copies/ml at week 48. Forty patients (12 men and 28 women; mean age +/- SD: 40 +/- 9 years) were included. Treatment was changed during the study for two patients (pregnancy, tuberculosis); one patient was lost to follow-up and one patient died (gastroenteritis with cachexia). At week 48, 78% [95% confidence interval (CI): 65-90%] and 68% (95% CI: 53-82%) of the patients had HIV-1 RNA <400 and <50 copies/ml, respectively (intent-to-treat analysis; not completer = failure). Among the seven patients with HIV-1 RNA >or=400 copies/ml at week 48, five were not compliant; genotyping analysis (n = 4) did not reveal a major mutation for protease inhibitors. The mean CD4 cell count change from baseline to week 48 was +238 +/- 79 cells/mm(3). The combination of unboosted atazanavir with lamivudine and didanosine was efficient and well tolerated in HIV-1-infected patients with results similar to those observed in Northern countries. These results suggest that unboosted atazanavir with its high genetic barrier could be a valuable alternative to NNRTIs in resource-limited countries in some HIV-1-infected patients in case of compliance issues with NNRTIs, intolerance to NNRTIs, resistance mutations to NNRTIs, in women with childbearing potential, or as a maintenance therapy in patients with virological suppression.

Objective: To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal., Design and Methods: This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent-to-treat., Results: The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 +/- 92/mcL (+/- standard deviation [SD]; range 1-346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 +/- 0.4 log(10) copies/mL (+/- SD; range 4.6-5.9). The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18. The mean increase in the CD4+ cell count was 105 +/- 125/mcL (n = 38) at M3 and 186 +/- 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation., Conclusion: Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment-limiting side effects.