Drug Resistance After 2nd-Line Failure Can Be Managed Using WHO-Recommended Regimens in Nigeria

Background: In sub-Saharan Africa only a limited number of antiretroviral drugs is available. Virological failure, and subsequent drug resistance, during second-line treatment can therefore have substantial clinical ramifications as it can result in complete loss of therapeutic options. The Institute for Human Virology-Nigeria (IHVN), a US PEPFAR implementing partner, provides antiretroviral therapy (ART) to over 150,000 public and private sector patients through the AIDS Care and Treatment in Nigeria (ACTIONPlusUp) Program. We determined the extent to which virological failure during second line treatment with LPV/r, ATVr results in the loss of treatment options to WHO recommended treatment regimens at two IHVN PEPFAR supported sites in Abuja. Methodology: Plasma samples from patients who failed LPV/r and ATV/r- based second-line regimens from January to August 2013 were assayed for HIV-1 RNA viral load (VL). Plasma virus from samples with VL >1000 cp/mL at time of failures were sequenced in the pol gene. The genotypes were interpreted using the Stanford HIV db interpretation program (version 6.3.1). We assigned the following genotypic susceptibility scores (GSS) to the 5 levels of resistance included in the Stanford HIV db program: 0, 0.25, 0.50, 0.75, and 1 for respectively the high-level resistance, intermediate resistance, lowlevel resistance, potential low-level resistance, and susceptible. We then calculated the GSS to the first-, second-, and third-line regimens recommended by WHO as the arithmetic sum of the individual GSS. We defined loss of drug options as a GSS of zero to any WHO recommended regimen. Exhaustion of drug options was defined as a GSS<2. Results: Of the 936 HIV-infected patients receiving second-line ART, 56 (6.0%) were adults with confirmed virological failure. The mean (SD) HIV RNA and age were 5.1log10 (0.79) cp/mL, and 34.8 (15.6) years, respectively. A total of 9 sequences contained no drug resistance mutations. The five most frequently observed mutations were K103N (22.4%), M184V (20.4%), M41L (20.4%), M46I (19.4%) and I54V (15.3%). Complete loss of treatment options was only found in one patient (2%), with virus still susceptible to a second generation NNRTI. Exhaustion of drug options to first- and second line regimens was found in 16 patients (32%). If second generation NNRTIs and newer boosted protease inhibitors become available, then exhaustion of drug options will be reduced to 22%. Conclusions: Complete loss of treatment options is very rare after failure to second-line treatment in Nigeria. Exhaustive loss of treatment options occurs in less than one out of three patients and can be partially avoided by providing third-line regimens. In most patients an active treatment regimen can be given after failure with second-line treatment.