Intensive campaigns to improve availability of ART worldwide is paying off and most African countries are currently able to provide first-line ART regimens to a considerable number of HIV-1 infected individuals in need of treatment. Efforts to scale-up laboratory facilities for treatment monitoring in these patients however are running behind. A random sample survey is often the only way to assess treatment efficacy and the selection of drug resistance in treatment programs in Africa. The information obtained from these surveys is important for eventual future adaptation of treatment strategies. Moreover, resistance data obtained from these surveys will be crucial in evaluating the value of second-line regimens in Africa where only limited drugs are available.
In this study, 85.6% of the patients receiving ART ≥ 6 months had a VL<50 copies/ml. These figures are comparable to what has been published for other African regions [7–10]. The high treatment success rate seen in this study might be partly due to a bias because of possible selection of patients who attend the CCC more regularly. These patients could be more motivated and having a better treatment adherence. Although the total number of patients was small, a significant correlation between adherence and treatment success was demonstrated.
Despite the overall high efficacy of ART treatment regimens, a significant accumulation of resistance mutations was observed in patients with a detectable viral load at 6 months or more after treatment initiation. Though we cannot excluded that some of these mutations were already present at baseline, we assume that most of them were selected during treatment. As mutations can only be selected in the presence of the drug, their detection excludes the poor-intake of medication as the main reason for failure.
The combinations of AZT/d4T+3TC+EFV/NVP are extensively used as a first-line regimen in RLS . Despite known toxicity of d4T, this drug is still commonly used in RLS as a component of the low-cost generic fixed dose combinations. 3TC, EFV and NVP have a low genetic barrier towards resistance and it is therefore not unexpected that, in accordance with the results of other studies, the 3TC mutation M184V and the NNRTI mutations K103N, 190G and 181C are frequently observed in case of treatment failure [8, 12]. The high percentage (62.5%) of patients with a combination of M184V mutations and at least one NNRTI resistance associated mutation, as well as the selection of the broad NRTI cross-resistance mutations Q151M and K65R in 3 patients are worrying.
K65R mutations have previously been described among populations with similar subtypes . However, this was mainly among patients receiving a TDF containing regimen which is known to induce the K65R mutation . However, the selection of K65R under a d4T containing regimen seems to be more common among non-B subtypes as observed by others [15, 16]. Despite the presence of the thymidine analogues AZT or d4T in most of the regimens, thymidine analogue mutations (TAMs) were infrequently observed.
Accumulation of mutations against drugs from different drug classes and/or the presence of broad cross-resistance mutations will jeopardize the effectiveness of the NRTI backbone of second-line regimens that often include ABC and TDF. Moreover, the limited availability and the high cost of boosted PIs force clinicians in RLS to recycle NNRTIs in the second-line regimen. Based on the resistance data from this study, we can assume that the effect of such a second-line regimen will be at the most temporary.
The small number of patients on a second-line regimen that were included and the limited time period between initiation of this regimen and the date of sampling, did not allow us to make conclusions about the efficacy of second-line regimens.
In conclusion, the results of this observational study show that effective first-line ART in clinical care centres with limited resources is feasible. However, the resistance data point out the danger of the absence of viral monitoring, with regard to the accumulation of resistance mutations.
Besides high quality adherence counselling, efforts are needed to guarantee a robust supply of drugs from different classes, as well as the worldwide availability of affordable and simple viral load and genotyping assays to ensure long-term success of global ART programs.