PAPER:Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis

Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis

Important Quotation:

1. 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

2.The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. 

3. These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period 

4. and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections

5. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. 

6. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.

Reference:

Drake, A. L., Wagner, A., Richardson, B., & John-Stewart, G. (2014). Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis. PLoS medicine, 11(2), e1001608.

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.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Worldwide, about 3.4 million children younger than 15 years old (mostly living in sub-Saharan Africa) are infected with HIV, the virus that causes AIDS by gradually destroying immune system cells, thereby leaving infected individuals susceptible to other serious infections. In 2012 alone, 230,000 children (more than 700 every day) were newly infected with HIV. Most HIV infections among children are the result of mother-to-child HIV transmission (MTCT) during pregnancy, delivery, or breastfeeding. The rate of MTCT (and deaths among HIV-positive pregnant women from complications related to HIV infection) can be greatly reduced by testing women for HIV infection during pregnancy (antenatal HIV testing), treating HIV-positive women with antiretroviral drugs (ARVs, powerful drugs that control HIV replication and allow the immune system to recover) during pregnancy, delivery, and breastfeeding, and giving ARVs to their newborn babies.

Why Was This Study Done?

The World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed a global plan that aims to move towards eliminating new HIV infections among children by 2015 and towards keeping their mothers alive. To ensure the plan's success, the incidence of HIV (the number of new infections) among women and the rate of MTCT must be reduced by increasing ARV uptake by mothers and their infants for the prevention of MTCT. However, the risk of HIV infection among pregnant women and among women who have recently given birth (postpartum women) is poorly understood because, although guidelines recommend repeat HIV testing during late pregnancy or at delivery in settings where HIV infection is common, pregnant women are often tested only once for HIV infection. The lack of retesting represents a missed opportunity to identify pregnant and postpartum women who have recently acquired HIV and to prevent MTCT by initiating ARV therapy. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a study that uses statistical methods to combine the results of several studies), the researchers estimate maternal HIV incidence during pregnancy and the postpartum period, and compare the risk of MTCT among women with incident (new) and chronic (long-standing) HIV infection.

What Did the Researchers Do and Find?

The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. They used random effects statistical models to estimate the pooled HIV incidence rate and cumulative HIV incidence (the number of new infections per number of people at risk), and the association between pregnancy/postpartum status and HIV incidence and MTCT risk and rates. The pooled HIV incidence rate among pregnant/postpartum women estimated from 19 studies (all from sub-Saharan Africa) that reported HIV incidence rates was 3.8/100 person-years. The pooled cumulative HIV incidence was significantly higher in African countries than in non-African countries (3.6% and 0.3%, respectively; a “significant” difference is one that is unlikely to arise by chance). In the five studies that provided suitable data, the risk of HIV acquisition was similar in pregnant, postpartum, and non-pregnant/non-postpartum women. Finally, among African women, the risk of MTCT was 2.9-fold higher during the postpartum period among those who had recently acquired HIV than among those with chronic HIV infection, and 2.3-fold higher during the pregnancy/postpartum periods combined.

What Do These Findings Mean?

These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections. However, the small number of studies included in this meta-analysis and the use of heterogeneous research methodologies in these studies may limit the accuracy of these findings. Nevertheless, these findings have important implications for the global plan to eliminate HIV infections in children. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.

STRENGTH, LIMITATION ADN CONCLUSION

Our systematic review and meta-analysis had several strengths. We used a broad search strategy that included peer-reviewed articles in addition to conference abstracts presented at recent HIV conferences. We also contacted authors to acquire additional data for some summary measures. Two independent reviewers evaluated full-text articles for relevance and abstraction of data. HIV incidence rates, cumulative HIV incidence, and risk of HIV acquisition were pooled separately by pregnancy and postpartum status, as well as together, to better understand risks specific to pregnancy versus the postpartum period. To complement the meta-analysis of HIV incidence, we also pooled MTCT rates among mothers with incident infection, and compared the risk of MTCT for women with incident versus chronic infection.

Our analysis is subject to limitations resulting from pooling data from studies with heterogeneous research methodologies. Incident HIV infections reported in the studies were estimated using tests that varied in sensitivity and with different intervals for follow-up testing. Variability in test performance has previously been noted to result in overestimation of incidence when lower sensitivity tests are used initially and higher sensitivity tests for subsequent tests [49]. Timing of seroconversion is also related to timing of testing; women seeking antenatal care and testing earlier in their pregnancy have more person-time and opportunity to be detected as an incident rather than chronic infection. Conversely, seroconversions early in pregnancy are not captured as incident infections if antenatal care is sought later. Another limitation of this analysis is that cumulative incidence based on repeat testing was estimated from cohorts with differing duration of follow-up and cross-sectional testing using sensitive assays. While the performance of assays for detecting recent infections has been shown to vary across HIV clades and subpopulations, a recent study suggests pregnancy does not influence performance of BED or avidity assays [50],[51]. However, there is considerable evidence that early iterations of testing algorithms for incident infection misclassified a proportion of individuals with chronic infections as incident infections (false recent rate) and prompted the World Health Organization to issue guidance on conducting assays, with specific criteria for appropriate sampling designs, sample size, and statistical analysis considerations [51]. Thus, inclusion of different assays and testing algorithms likely overestimates our pooled cumulative incidence. These differences partially explain why our estimates of pooled cumulative incidence and pooled incidence rate differ. While we were unable to adjust for national HIV prevalence at the time of the study—since HIV prevalence estimates are not available for all countries and years included in this meta-analysis—we did consider African region as a marker of HIV prevalence; however, this approach may result in residual confounding. In addition, none of the included studies were primarily designed to estimate HIV incidence in pregnancy and the postpartum period; most studies excluded pregnant women from initial study participation, and report HIV incidence during pregnancy and postpartum as a secondary research objective, limiting generalizability. Finally, the number of studies included in our meta-regression models was small; therefore, the models may lack power to detect associations and are unable to ascertain multiple potential sources of confounding.

In conclusion, HIV incidence among pregnant and postpartum populations was high in this meta-analysis and may substantially increase risk of MTCT. Our results have several implications for antenatal care/PMTCT programs. First, women in high prevalence settings should be offered repeat HIV testing to detect incident infections and to diagnose women in the postpartum period who did not receive antenatal care. This approach is beneficial because it detects maternal HIV infection while women are accessing the health care system and prompts referral to appropriate HIV care and treatment. While specific recommendations regarding ARV regimens for women with incident infection do not currently exist, maternal ART during pregnancy is likely the best option given high maternal viral loads during incident infection. Second, there is a need for wider distribution of more sensitive HIV tests, such as the fourth generation rapid tests, to enhance early detection of incident HIV. These more sensitive assays, which detect both HIV antibodies and HIV p24 antigen, can reduce the number of women who have early HIV infection and are incorrectly classified as HIV negative. Third, since pregnant and postpartum women are a vulnerable population at risk of HIV and sexually transmitted infections, they should receive continued counseling on the need for condoms to prevent transmission during this time. Pregnant and postpartum populations should also be considered, and included early in the process, of developing and evaluating female-controlled prevention methods, such as microbicides, for safety and efficacy [52].