HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya

Abstract

BackgroundHIV-1 molecular epidemiology amongst men who have sex with men (MSM) in sub-Saharan Africa remains not well characterized. We aimed to determine HIV-1 subtype distribution, transmission clusters and transmitted drug resistance (TDR) in acute and early infected MSM from Coastal Kenya.MethodsAnalysis of HIV-1 partial pol sequences from MSM recruited 2005–2017 and sampled within six months of the estimated date of infection. Volunteers were classified as men who have sex with men exclusively (MSME) or with both men and women (MSMW). HIV-1 subtype and transmission clusters were determined by maximum-likelihood phylogenetics. TDR mutations were determined using the Stanford HIV drug resistance database.ResultsOf the 97 volunteers, majority (69%) were MSMW; 74%, 16%, 9% and 1% had HIV-1 subtypes A1, D, C or G, respectively. Overall, 65% formed transmission clusters, with substantial mixing between MSME and MSMW. Majority of volunteer sequences were either not linked to any reference sequence (56%) or clustered exclusively with sequences of Kenyan origin (19%). Eight (8% [95% CI: 4–16]) had at least one TDR mutation against nucleoside (n = 2 [2%]) and/or non-nucleoside (n = 7 [7%]) reverse transcriptase inhibitors. The most prevalent TDR mutation was K103N (n = 5), with sequences forming transmission clusters of two and three taxa each. There were no significant differences in HIV-1 subtype distribution and TDR between MSME and MSMW.ConclusionsThis HIV-1 MSM epidemic was predominantly sub-subtype A1, of Kenyan origin, with many transmission clusters and having intermediate level of TDR. Targeted HIV-1 prevention, early identification and care interventions are warranted to break the transmission cycle amongst MSM from Coastal Kenya.

Genetic transmission networks of HIV-1 CRF07_BC strain among HIV-1 infections with virologic failure of ART in a minority area of China: a population-based study

“…Similar to K103N, M184V/I and Y181C can also be stably passaged without drug pressure [ 26 ] which may be the reason for the higher frequency of these drug resistance mutations in the transmission network. This finding was also observed in other undeveloped [ 25 ] and developed settings [ 27 , 28 ]. The widespread use of ART may have led to a considerable increase in HIV drug resistance and drug resistance transmission in newly infected individuals.…”

“…Among 40 drug resistance clusters, K103N was observed in 22 clusters as the common drug resistance site and was the most frequent drug resistance-associated mutation. The possible reason might be that K103N mutation can persist without drug pressure and promote infection to another host [23,24], which has been attributed to the widespread use of NNRTI in first-line ART [25]. Similar to K103N, M184V/I and Y181C can also be stably passaged without drug pressure [26] which may be the reason for the higher frequency of these drug resistance mutations in the transmission network.…”

HIV-1 Transmission Patterns Within and Between Risk Groups in Coastal Kenya

“…MSM-exclusive and IDU-exclusive clusters were more common than FSW and HET clusters. High rates of clustering among MSM and IDU have been described before, both in our setting and elsewhere, and have been linked to an elevated risk of infection among MSM and IDU within close networks 6,8,17,29,30,41 . Whereas the MSM sequences were found in several smaller clusters, the vast majority of the IDU sequences formed one large cluster.…”

“…Sequences sampled from the same individuals were excluded from the data set, retaining only the oldest sequence per participant. Risk group information was obtained from LANL and any missing data were obtained by communication with study authors or inferred from reviewing literature from the respective studies 6,[8][9][10][11][12][13][14][15] . In addition, new HIV-1 pol sequences were generated from samples collected 2005-2019 participants in an acute HIV-1 infection cohort and from a prospective observational study following high-risk volunteers in an HIV-1 vaccine feasibility cohort described elsewhere 3 .…”

Uptake of antiretroviral treatment and viral suppression among men who have sex with men and transgender women in sub-Saharan Africa in an observational cohort study: HPTN 075

“…Information on HIV drug resistance among MSM in Africa is limited. In prior studies from Kenya and Nigeria, the rates of drug resistance among MSM who reported that they were ART-naive or initiating ART were 8.2% ( Hassan et al, 2018 ) and 9.7% ( Crowell et al, 2020 ), respectively. The study from Nigeria also detected drug resistance in 43% of ART-experienced MSM ( Crowell et al, 2020 ).…”