Chaplin B., Eisen G., Idoko J., Onwujekwe D., Idigbe E., Adewole I., Gashau W., Meloni S., Sarr A.D., Sankalé J.L., Ekong E., Murphy R.L., Kanki P.
Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Jos University Teaching Hospital, Plateau State, Nigeria; National Institute of Medical Research, Lagos, Nigeria; University College Hospital, Ibadan, Nigeria; Univer
Chaplin, B., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Eisen, G., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Idoko, J., Jos University Teaching Hospital, Plateau State, Nigeria; Onwujekwe, D., National Institute of Medical Research, Lagos, Nigeria; Idigbe, E., National Institute of Medical Research, Lagos, Nigeria; Adewole, I., University College Hospital, Ibadan, Nigeria; Gashau, W., University Maiduguri Teaching Hospital, Maiduguri, Nigeria; Meloni, S., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Sarr, A.D., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Sankalé, J.L., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Ekong, E., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; Murphy, R.L., Northwestern University, Chicago, IL, United States; Kanki, P., Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States
A diverse array of non-subtype B HIV-1 viruses circulates in Africa and dominates the global pandemic. It is important to understand how drug resistance mutations in non-B subtypes may develop differently from the patterns described in subtype B. HIV-1 reverse transcriptase and protease sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression was used to examine the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. The distribution of HIV-1 subtypes included CRF02-AG (45.0%), G (37.9%), CRF06-cpx (4.4%), A (3.6%), and other subtypes or recombinant sequences (9.2%). The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). Multivariate analysis showed that CRF02-AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) = 0.35; p = 0.022]. Subtype A patients showed a 42.5-fold increased risk (AOR = 42.5, p = 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR = 2.40, p = 0.036) and V106I (AOR = 6.15, p = 0.010), whereas subtype CRF02-AG patients had an increased risk for V90I (AOR = 3.16; p = 0.003) and a decreased risk for A98G (AOR = 0.48, p = 0.019). Five RT mutations were found to vary significantly between different non-B West African subtypes. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings. © Copyright 2011, Mary Ann Liebert, Inc.