Prevalence of HIV-1 Drug Resistance among Women Screening for HIV Prevention Trials in KwaZulu-Natal, South Africa (MTN-009)

Background:A major concern with using antiretroviral (ARV)-based products for HIV prevention is the potential spread of drug resistance, particularly from individuals who are HIV-infected but unaware of their status. Limited data exist on the prevalence of HIV infection or drug resistance among potential users of ARV-based prevention products.Methods:A cross-sectional study of reproductive-aged women who presented to screen for an HIV prevention trial was conducted at 7 clinical sites in Durban, South Africa. CD4+T cell counts, HIV-1 RNA levels and population sequencing of the protease and reverse transcriptase genes were performed for all women with 2 positive HIV rapid tests. Resistance mutations were identified using the Stanford Calibrated Population Resistance Tool.Results:Of the 1073 evaluable women, 400(37%) were confirmed as HIV-infected. Of those, plasma HIV-1 RNA was detectable in 365/400(91%) and undetectable(200 copies/ml) analyzed for drug resistance, 26(7.4%) had nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) drug resistance mutations. Among those with resistance, 18/26 participants(62%) had single-class NNRTI resistance and 5/26(19%) had dual-class NRTI/NNRTI. Major mutations in reverse transcriptase included K65R(n = 1), L74I(n = 1), K103N(n = 19), V106M(n = 4), Y181C(n = 2), M184V(n = 4), and K219E/R(n = 2). Major PI-resistance mutations were rare: M46L(n = 1) and I85V(n = 1). All participants were infected with subtype C virus, except one infected with subtype A.Conclusions:In women from Durban, South Africa screening for an HIV prevention trial, the HIV prevalence was high (37%) and HIV drug resistance prevalence was above 5%. This study highlights the potential challenges faced when implementing an ARV-based prevention product that overlaps with first-line antiretroviral therapy. Effective screening to exclude HIV infection among women interested in uptake of ARV-based HIV prevention will be essential in limiting the spread of ARV resistance

CD4+ T Cell Counts and HIV-1 RNA Levels of HIV-1 Positive Participants.

<p>Histogram showing frequency of HIV positive participants (n = 400) that have (A) CD4+ T cell counts <200 cells/mm³ indicating risk for AIDS, 200–349 cells/mm³ indicating treatment eligibility, and >350 cells/mm³; and (B) varying levels of HIV-1 RNA (copies/ml).</p

Demographic Factors for All Evaluable Participants and the Subset that was HIV Positive and Tested for Drug Resistance in MTN-009.

<p>Notes: SD = Standard Deviation.</p

Consort Diagram.

<p>Consort Diagram.</p

Major Drug Resistance Mutation Profiles Detected.

<p>Major Drug Resistance Mutation Profiles Detected.</p

Frequency of ARV Resistance Mutations.

<p>Histogram showing number of women with drug resistant HIV infection that had each of the following protease inhibitor (PI), nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations M46L, I85V, K65R, L74I, K219E, M184V, K101E, V106M, Y181C or G190A. Resistance mutations were identified using the Stanford Calibrated Population Resistance Tool.</p