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

Abstract

BackgroundReducing 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).MethodsWe 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.ResultsFrom 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).ConclusionsMaternal 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.

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

“…A systematic review has demonstrated a correlation between a herpes simplex virus type 2 (HSV‐2) diagnosis and HIV vertical transmission (odds ratio [OR] 1.57). However, studies did not always adjust for key confounders such as ART use and mode of delivery .…”

The Tat Protein of HIV-1 Prevents the Loss of HSV-Specific Memory Adaptive Responses and Favors the Control of Viral Reactivation

“…The development of preventive and therapeutic vaccines against Herpes Simplex Virus (HSV) is a global health priority for many reasons: (1) genital herpes affects half a billion people between the ages of 15 and 49 worldwide [ 1 , 2 ], causing diseases which are particularly severe and potentially lethal in newborns and immunocompromised hosts; (2) HSV infection is one of the worldwide leading causes of encephalitis, with high hospitalization and mortality rates when compared with other etiologic causes, especially in immunosuppressed and elderly hosts [ 3 , 4 ]; (3) HSV-1 and 2 infections have also been associated with the onset and morbidity of different non-communicable diseases, such as Alzheimer’s disease [ 5 ] and atherosclerosis [ 6 ] and with an increased risk of horizontal and vertical HIV acquisition and transmission [ 7 , 8 ] and bacterial vaginosis [ 9 ].…”

Toll‐like receptors as novel therapeutic targets for herpes simplex virus infection

“…Moreover, these genital lesions favor acquisition of other STIs, in particular, human immunodeficiency virus type 1 (HIV1) . Shedding of HSV2 from the genital tract is recurrent and asymptomatic . Intermittent antiviral therapy can suppress current infections while prophylactic use can prevent further relapses.…”