HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

PLoS One. 2018 May 9;13(5):e0196451. doi: 10.1371/journal.pone.0196451. eCollection 2018.

Abstract

Background: Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care.

Objectives: To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART).

Methods: Samples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery.

Results: Ninety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts <350 c/mm3 and 30% were previously not on ART. Thirteen women (14%) had at least one HIVDRM of whom 70% were not on previous ART. Eight women (13%) had at least one HIVDRM at delivery. Out of 37 women with data available from the two time points, 8 (21%) developed at least one new HIVDRM during pMTCT or ART. Twenty seven per cent (53/191), 32% (44/138) and 100% (5/5) of the mutations that were present at enrolment, delivery and that emerged during pregnancy, respectively, were minority mutations (frequency <20%).

Conclusions: Even with ultrasensitive HIV-1 genotyping, less than 20% of women with detectable viremia at delivery had HIVDRM before initiating pMTCT or ART. This suggests that factors other than pre-existing resistance, such as lack of adherence or interruptions of the ANC chain, are also relevant to explain lack of virological suppression at the time of delivery in women receiving antiretrovirals drugs during pregnancy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count / methods
  • Drug Resistance, Viral / drug effects*
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Mozambique
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Prenatal Care / methods
  • Young Adult

Substances

  • Anti-HIV Agents

Grants and funding

This work was supported by the European Developing Countries Clinical Trials Partnership (EDCTP; IP.2007.31080.002) to Clara Menéndez, the Malaria in Pregnancy Consortium and the following national agencies: Instituto de Salud Carlos III (PI08/0564), Spain to Clara Menéndez. Raquel González and María Rupérez were partially supported by grants from the Spanish Ministry of Health (ref. CM07/0015 and CM11/00278, respectively). The CISM receives core funding from the Spanish Agency for International Cooperation (AECI). Manhiça District Hospital HIV programme receives funding from the Agencia Catalana de Cooperació al Desenvolupament. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.