Prevalence of HIV-1 pretreatment drug resistance among treatment naïve pregnant women in Bissau, Guinea Bissau

Abstract

Background: With increased access to antiretroviral treatment (ART) in sub-Saharan Africa emergence of HIV-1 pretreatment drug resistance constitutes a serious risk. This may lead to rapid virological failure in subjects initiating ART, and mother-to-child transmission despite prophylaxis.

Methods: Treatment-naïve pregnant women from four antenatal care clinics in Bissau, Guinea-Bissau, were enrolled from October 2016 to November 2017. Genotypic resistance testing and phylogenetic subtype analysis was performed on 48 specimens.

Results: Forty eight women met the survey inclusion criteria. All specimens were successfully amplified and genotyped. Specimens from five women were associated with HIV-1 drug resistance mutations. Four carried mutations exclusively linked to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (K103N, K103N/S) and one carried mutations to both NNRTIs (G190S, K101E) and nucleoside reverse transcriptase inhibitors (NRTIs) (M184V). These results corresponded to 10.4% (95% CI: 4.5-22.2%), 2.1% (95% CI: 0.4-10.9%) and 0% (95% CI: 0.0-7.4%) drug resistance mutations to NNRTIs, NRTIs and protease inhibitors, respectively. HIV-1 circulating recombinant form 02AG was most commonly found, followed by HIV-1 sub-subtype A3. Subtype/CRF was not associated with drug resistance mutations.

Conclusion: Our study reports a 10.4% prevalence of pretreatment drug resistance to NNRTIs in HIV-1-infected pregnant women in the capital Bissau, Guinea Bissau. Since NNRTIs are part of first-line ART in the country, baseline resistance screenings or adjustment of national treatment guidelines should be considered as antiretroviral treatment programs are scaled up.

Fig 1. Maximum likelihood phylogenetic analysis of HIV-1 pol sequences (specimen names are indicated at tips in black font) from 48 women residing in Bissau, together with HIV-1 reference sequences (in green font), showed that sequences of the study participants belonged to five different subtypes/CRFs (highlighted within a box shaded pink, where the subtype/CRF names are shown to the right).

One sequence (Plk_9) represented a putative recombinant between CRF06_cpx and CRF02_AG (indicated by an asterisk). Red internal branches indicate highly supported branches (aLRT-SH ≥0.90) while green internal branches indicate well-supported branches (0.87 ≤ aLRT-SH <0.90). The prefix of the taxa names indicates the collection site (BM, Bairro Militar Health Centre; A, Antula Health Centre; Q, Quelele Health Centre; and Plk, Plack-II Health Centre). The length of the horizontal bar below the phylogenetic tree corresponds to 0.02 nucleotide substitutions/site.