Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis

Abstract

Background: Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.

Methods and findings: We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0-4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5-2.1) or postpartum women (HR 1.1, 95% CI 0.6-1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2-3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2-4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.

Conclusions: Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to "high risk" cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.

Figure 1. Flowchart of studies reviewed and included in meta-analyses.

**Not mutually exclusive. †One study excluded that reported relative risk rather than hazard ratio.

Figure 2. Forest plot of HIV incidence rates, by pregnancy and postpartum status.

PY, person-years. *Defined as lactating.

Figure 3. Forest plot of HIV incidence rates during pregnancy and postpartum, by African region.

PY, person-years. *Defined as lactating.

Figure 4. Forest plot of cumulative incidence of incident HIV infection during pregnancy and postpartum, by testing algorithm.

The retested cumulative incidence category is calculated as the number of new infections per number at risk for studies, and the assay cumulative incidence category is calculated based on cross-sectional testing of HIV-positive samples using assay algorithms designed to detect incident infections; cumulative incidence expressed as percent for both retested and assay categories. NAAT, nucleic acid amplification test; STARHS*, STARHS using BED capture enzyme immunoassay; STARHS**, STARHS using bioMerieux Vironosticka less sensitive enzyme immunoassay.

Figure 5. Forest plot of risk of HIV acquisition, by pregnancy and postpartum status.

Figure 6. Forest plot of mother-to-child HIV transmission rates among women with incident infection during pregnancy/postpartum.

*No PMTCT ARVs. **Unspecified ARV regimen. †Single-dose nevirapine if maternal CD4 count >200 cells/mm³ and ART for women with CD4 count ≤200 cells/mm³. ††Zidovudine and nevirapine regimens for women and infants.

Figure 7. Effect of incident maternal HIV infection and antiretroviral prophylaxis on mother-to-child HIV transmission.

Incident infection defined as maternal HIV acquisition during pregnancy or postpartum; chronic infection defined as established HIV infection during pregnancy or postpartum. MTCT rates and ORs are derived from the studies indicated in parentheses; PMTCT ARVs represent the regimens available during the studies. For Moodley , women with CD4 count >200 cells/mm³ were eligible to receive ART; all other women received single-dose nevirapine regimens. For Singh , women were assumed to receive ART as per national guidelines in place during the study.

Figure 8. Forest plot of risk of mother-to-child HIV transmission and maternal HIV infection status.