title: Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009).
abstract: 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(<40 copies/ml) in 35/400(9%) women. 156 women(39%) were eligible for antiretroviral therapy (CD4+T cell counts<350 cells/mm(3)) and 50(13%) met criteria for AIDS(CD4<200 cells/mm(3)). Of 352 plasma samples(>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.
authors.affiliation: Department of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America. ump3@pitt.edu
authors.forename: Urvi M
authors.initials: UM
authors.lastname: Parikh
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Shayhana
authors.initials: S
authors.lastname: Ganesh
authors.forename: Kailazarid
authors.initials: K
authors.lastname: Gomez
authors.forename: Stephanie
authors.initials: S
authors.lastname: Horn
authors.forename: Krista
authors.initials: K
authors.lastname: Eskay
authors.forename: Cliff
authors.initials: C
authors.lastname: Kelly
authors.forename: Barbara
authors.initials: B
authors.lastname: Mensch
authors.forename: Pamina
authors.initials: P
authors.lastname: Gorbach
authors.forename: Lydia
authors.initials: L
authors.lastname: Soto-Torres
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006679:HIV Seropositivity / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008403:Mass Screening; D009154:Mutation; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D013019:South Africa / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease