Association between HIV-1 subtype and drug resistance in Nigerian infants

Abstract

Background: Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged ,18months, to explore the association between subtypes and patterns of resistance. Methods: Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher’s exact test and logistic regression analysis, controlling for geographical region and exposure. Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014; 9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had 1 NNRTI mutation, 92 infants (21.7%) had 1 NRTI mutation and 6 infants (1.4%) had 1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P"0.006), as was 70R (OR 23.1, P"0.007), 184I/V (OR 2.92, P"0.020), the presence of 1 thymidine analoguemutation (TAM) (OR 3.87, P"0.014), 1 type 2 TAM (OR 7.61, P"0.001) and 1 NRTI mutation (OR 3.26, P"0.005). Conclusions: This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I.