Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

Clin Infect Dis. 2019 Jul 18;69(3):523-529. doi: 10.1093/cid/ciy909.

Abstract

Background: A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART).

Methods: HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network-020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring.

Results: Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42).

Conclusions: The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring.

Clinical trials registration: NCT016170096 and NCT00514098.

Trial registration: ClinicalTrials.gov NCT01617096 NCT00514098.

Keywords: HIV drug resistance; antiretroviral therapy outcomes; antiretroviral treatment; dapivirine vaginal ring.

Publication types

  • Clinical Trial, Phase III
  • Observational Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Africa
  • Anti-HIV Agents / administration & dosage*
  • Contraceptive Devices, Female*
  • Disease Progression
  • Female
  • HIV
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV Seropositivity
  • Humans
  • Pyrimidines / administration & dosage*
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Vagina / virology
  • Young Adult

Substances

  • Anti-HIV Agents
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • Dapivirine

Associated data

  • ClinicalTrials.gov/NCT01617096
  • ClinicalTrials.gov/NCT00514098