Efficacy and safety of three second-line antiretroviral regimens in HIV-infected patients in Africa

Abstract

Objective:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.Design:ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.Methods:Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000 copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50 copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.Results:Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200 copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval –5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval –4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100 000 copies/ml (n = 122) had a viral load below 50 copies/ml at week 48 (37.7 versus 75.4%; P < 0.001).Conclusions:The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.

Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa

“…Exposure to viremia for a longer period is associated with higher mortality [23,24], and second-line treatment in Africa is less effective with high baseline viral load, likely a sign of prolonged viremia on first-line [44]. AIDS defining events prior to second-line switch are also associated with worse second-line outcomes [45].…”

Field evaluation of an open and polyvalent universal HIV-1/SIVcpz/SIVgor quantitative RT-PCR assay for HIV-1 viral load monitoring in comparison to Abbott RealTime HIV-1 in Cameroon

“…HIV-1 RNA VL results were compared for 474 samples from HIV-1 positive patients on first-line antiretroviral treatment (ART). Patients were attending HIV services of the Central and Military Hospitals of Yaoundé in Cameroon for the screening visit prior to inclusion in the ANRS12169/2-LADY Trial, designed to evaluate the efficiency of different second-line ART regimens (Ciaffi et al, 2015). Whole blood was collected on EDTA tubes and sent within six hours to the laboratory of CREMER.…”

The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates

“…14–18 We believe provision of resistance results will promote improved adherence, both for those without significant drug resistance who are presented with information that their virus remains fully susceptible to first line regimens, and for those with drug resistance who are transitioned to more potent protease inhibitor-based regimens. 19,20 For our primary outcome analysis, we will use a two-sample test of binomial proportions to compare the proportions of participants in each arm who achieve virologic suppression at study conclusion.…”