Abstract Body

Background: Antiretroviral drugs may produce different mutation patterns in different HIV-1 subtypes. We report here on the appearance of drug resistance mutations unique to etravirine and rilpilvirine exposure occurring in Kenyan patients with non-B subtypes failing first line therapy with neviripine or efavirenz. Methodology: RV288 is a multi-center PEPFAR Basic Program Evaluation that is being conducted in Kenya, Tanzania, Uganda and Nigeria. This cross-sectional study will estimate the rate of virologic suppression of patients on first-line HAART in PEPFAR clinics and identify predictors of virologic suppression and immunologic recovery. Patients on HAART for at least 6 months were randomly selected from 7 different hospitals for a one-time study visit. Labs performed included a viral load, clinical chemistries and hematology, absolute CD4+ lymphocyte count and CD4+ cell percentage. Subjects with a viral load > 1000 cps/ml were referred for adherence counseling while a sample was submitted for genotypic resistance testing. Viral load (HIV RNA) was quantified from plasma by PCR using Roche Amplicor Version 1.5 with lower detection limit of 400 copies/ml. Results: We found 617 out of 975 subjects (63%) had viral load <400cps/ml. Of 215 samples submitted for resistance testing, 115 (53%) had one or more resistance mutations. Interestingly, 14 of these subjects (13.8%) had an amino acid substitution at reverse transcriptase position 138 (A, G, K or Q; Table 1). These mutations are selected by etravirine and rilpivirine in subtype B viruses, reducing viral susceptibility to these drugs. Yet no subject had ever been exposed to either of these drugs. All subjects were failing either on efavirenz or nevirapine, which are not reported to produce mutations at this position, at least for subtype B viruses. All subjects had subtype A1 or D virus. Conclusions: The potential for patients to acquire E138 mutations from efavirenz or nevirapine has not previously been reported. This increases the chances of patients failing these drugs to have cross resistance with etravirine and rilpivirine, which can occur by other mutations as well (e.g. Y181C,I; M230L) and emphasizes the importance of resistance testing in resource-constrained settings.