Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial

Clin Infect Dis. 2022 Sep 10;75(4):586-595. doi: 10.1093/cid/ciab1027.

Abstract

Background: Globally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM).

Methods: Within a randomized trial of the effect of 3 contraceptive methods-DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant-on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method.

Results: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65-.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78-4.48).

Conclusions: In a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods.

Trial registration: ClinicalTrials.gov number NCT02550067.

Keywords: Africa; HIV; contraception; herpes simplex virus type 2 (HSV-2); women.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Contraception / adverse effects
  • Contraception / methods
  • Contraceptive Agents, Female* / adverse effects
  • Female
  • HIV Infections*
  • Herpes Simplex*
  • Herpesvirus 2, Human
  • Humans
  • Incidence
  • Intrauterine Devices, Copper* / adverse effects
  • Levonorgestrel
  • Male
  • Medroxyprogesterone Acetate / adverse effects

Substances

  • Contraceptive Agents, Female
  • Levonorgestrel
  • Medroxyprogesterone Acetate

Associated data

  • ClinicalTrials.gov/NCT02550067