Naturally occurring protease inhibitor resistance mutations and their frequencies in HIV proviral sequences of drug-naïve sex workers in Nairobi, Kenya

Abstract

Sub-Saharan Africa accounts for 69% of the people living with HIV globally. An estimated 1,600,000 Kenyans are living with HIV-1. Antiretroviral therapy (ART) has saved 9 million life-years in Sub-Saharan Africa. However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. Naturally occurring primary antiretroviral drug resistance mutations have not been well analyzed in ART naïve HIV+ patients in Kenya. Here we have examined protease inhibitor (PI) resistance mutations in ART naïve HIV-1 seropositive women in Pumwani sex worker cohort established in Nairobi, Kenya, wherein HIV-1 infection is predominantly caused by subtypes A and D viruses. We have analyzed consensus sequences of HIV protease from 109 drugnaïve patients, as a part of HIV-1 whole-genome sequencing using 454 sequencing methodology. Analysis using HIVdb program revealed a prevalence of 22% (24/109) PI resistance mutations among the study subjects. D30N (3.7%), M46I (0.9%) and V82F (0.9%) are the major mutations observed. D30N mutation is known to confer high-level resistance to nelfinavir. M46I and V82F confer resistance to indinavir, lopinavir, fosamprenavir and nelfinavir. In addition, many minor mutations were found at seven different drug resistance sites. It is important to study the implications of these mutations to the effectiveness of specific PI drug treatment. This study provides valuable data pertaining to primary drug resistance in Kenyan HIV-1 infected patients before ART became available.

Correlation of HIV-1 drug resistant mutations and virologic failure

“…Previous related studies [ 3 - 15 ] identified some of the mutations that were identified in this study, however, our study reports other several new mutations of clinical importance which were not reported in the previous studies. The existence of these new mutations that encode resistance to the present drugs the participants are currently undertaking.…”

“…In Kenya, mutations conferring resistance to available ARVs has been reported in past studies. These mutations included M184V, K65R,D67N,K70R,K219Q,Q151M, T215F, M41L, T69N, V75M, M41L, T69N, V75M, D67G, V75M, M184I, T215N, M41LM, T215N, K219N,210W, T215Y as NRTIs; K103N/S, Y181C/Y/I/V, G190A/S, L100I,V179T, V106I/A, V108I, P225H, M230L, K238T, P225H, F227L as NNRTIs; M46I/L, D30N,M46I,V82F,L90M as PIs [ 3 - 15 ]. However, these studies did not link the mutations with the viral tallies and ARVs the participants were taking.…”

High Level of HIV Drug Resistance and Virologic Nonsuppression Among Female Sex Workers in Ethiopia: A Nationwide Cross-Sectional Study

“…10,23–29 Consistent with our findings, other studies have reported high PDR levels (10%–48%) among FSWs in different countries, including those in sub-Saharan Africa. 28,30–34 Moreover, previous studies also have shown a higher PDR rate among communities and groups with high-risk behaviors. 29,35 This highlights the vulnerability of FSWs to HIVDR and the risk of onward transmission to the general population.…”

HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study

“…Regular surveillance for HIVDR in key affected groups such as SWs, is not routinely undertaken in South Africa, and available evidence globally is based upon very small samples from only a few locations. Amongst SW populations within Kenya, evidence suggests a 22% prevalence of HIVDR [ 21 ]. An unpublished Kenyan study suggested that 8.3% of ARV treated FSWs within the Pumwani cohort had HIVDR (5/60)[ 22 ].…”