Does maternal HSV-2 coinfection increase mother-to-child transmission of HIV? A systematic review

Abstract

Background: Reducing HIV mother-to-child transmission (MTCT) is critical to ending the HIV pandemic. Reports suggest that herpes simplex virus-2 (HSV-2), a common coinfection in HIV-infected individuals, is associated with increased MTCT, but results have been conflicting. We conducted a systematic review of observational studies to quantify the magnitude of this relationship (PROSPERO no. CRD42016043315).

Methods: We searched Medline (1981 to June week 3, 2016), EMBASE (1981 to week 26, 2016), relevant conferences (2013-2016) and bibliographies of identified studies for cohort and case-control studies enrolling HIV-positive women during pregnancy or peripartum that quantified the effect of HSV-2 infection on MTCT. The primary outcome was the risk of perinatal HIV transmission associated with maternal HSV-2 status. Risk of bias was evaluated using a standardised tool, and results were meta-analysed where appropriate using a random-effects model, with studies weighted using the inverse variance method.

Results: From 2103 hits, 112 studies were considered for inclusion, and 10 were ultimately included. Of the included studies, three used a case-control design, three were retrospective cohorts and four were prospective cohorts. Risk of bias was low in three studies, moderate in six and high in one. The median sample size was 278.5 mother-infant pairs (range: 48-1513). The most common strategy for classifying maternal HSV-2 status was type-specific serology (n=6), followed by genital shedding (n=3) or genital culture (n=3), clinical diagnosis of herpes (n=2) or genital ulcer disease (n=1). Results from five studies that provided quantitative estimates of the association between HSV-2 seropositivity and MTCT were meta-analysed, yielding a pooled unadjusted OR=1.17 (95% CI=0.69 to 1.96, I²=58%). Three of these studies further considered key confounding variables, specifically antiretroviral use and/or viral load (n=3), and mode of delivery (n=2), yielding a pooled adjusted OR=1.57 (95% CI=1.17 to 2.11, I²=0).

Conclusions: Maternal HSV-2 coinfection appears to be associated with increased perinatal HIV transmission. Further study of the effect of HSV-2 treatment on MTCT is warranted.

Keywords: HIV; coinfection; herpesvirus-2; human; infant; mother; transmission.

Figure 1

Flow chart of search strategy. ACOG, American Congress of Obstetricians and Gynaecologists; CAHR, Canadian Association of HIV Research; CROI, Conference on Retroviruses and Opportunistic Infections; IAS, International AIDS Society/World AIDS Conference; ICAAC, Interscience Conference on Antimicrobial Agents and Chemotherapy; IDSA, Infectious Diseases Society of America Annual Meeting; IDSOG, Infectious Diseases Society for Obstetrics and Gynaecology; SMFM, Society for Maternal Fetal Medicine; SOGC, Society of Obstetricians and Gynaecologists of Canada.

Figure 2

(A) Forest plot of the impact of HSV-2 seropositivity on MTCT (unadjusted analysis). (B) Forest plot of the impact of HSV-2 seropositivity on MTCT (adjusted analysis). (C) Forest plot of the impact of HSV-2 seropositivity on intrapartum MTCT (unadjusted analysis). HSV-2, herpes simplex virus-2; MTCT, mother-to-child transmission.