Maternal antiretroviral treatment for HIV infection and risk of small-for-gestational-age birth: A systematic review and meta-analysis of protease inhibitor-based treatment and timing of treatment.

BACKGROUND: Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before conception may be associated with adverse pregnancy outcomes. The risk of having a small-for-gestational-age (SGA) infant was examined among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception. METHODS: A search was conducted using PubMed, Embase, and the Cochrane Library, and a systematic review was performed of studies published since Dec 1, 1995. Effect estimates with 95% confidence intervals (CIs) were extracted and meta-analyses with random-effects models were conducted. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. FINDINGS: Of 783 identified studies, 28 fulfilled the inclusion criteria. Meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio [OR]: 1·09; CI: 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled OR: 1·08; CI: 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research questions, respectively. INTERPRETATION: Although the benefits of cART largely outweigh the risks, these findings indicate the possibility of slightly increased risks of having an SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.

Time trends in perinatal outcomes among HIV-positive pregnant women in Northern Tanzania: A registry-based study.

INTRODUCTION: Maternal HIV infection is associated with increased risk of having a preterm delivery, low birth weight baby, small for gestational age baby and stillbirth. Maternal use of combination antiretroviral treatment is also associated with preterm delivery and low birth weight, although the effects vary by the type of drugs and timing of initiation. OBJECTIVE: To examine time trends in adverse perinatal outcomes among HIV-positive compared with HIV-negative women. DESIGN: Registry-based cohort study. SETTING: Northern Tanzania, 2000-2018. STUDY SAMPLE: Mother-baby pairs of singleton deliveries (n = 41 156). METHODS: Perinatal outcomes of HIV-positive women were compared with HIV-negative women during time periods representing shifts in prevention of mother-to-child transmission guidelines. Monotherapy was used as first-line therapy before 2007 while combination antiretroviral treatment was routinely used from 2007. Log binomial and quantile regression were used to analyze the data. MAIN OUTCOME MEASURES: Preterm delivery, low birth weight, perinatal death, stillbirth, low Apgar score, transfer to neonatal care unit and small for gestational age. RESULTS: Overall, maternal HIV infection was associated with a higher risk of low birth weight and small for gestational age. Moreover, this pattern became more pronounced over time for low birth weight, the last time period being an exception. For other outcomes we found none or only a small overall association with maternal HIV infection, although a trend towards higher risk over time in HIV-positive compared with HIV-negative women was observed for preterm delivery and perinatal death. Quantile regression showed an increase in birth weight in babies born to HIV-negative women over time and a corresponding decline in birth weight in babies born to HIV-positive women. CONCLUSION: Unfavourable trends in some of the selected perinatal outcomes were seen for HIV-positive compared with HIV-negative women. Potential side-effects of combination antiretroviral treatment in pregnancy should be further explored.

Correction: Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study.

[This corrects the article DOI: 10.1371/journal.pone.0184362.].

Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study.

OBJECTIVE: To examine time trends in antenatal factors and delivery characteristics in Northern Tanzania, and relate these to national guidelines for HIV in pregnancy. DESIGN: Registry-based study. SETTING: Northern Tanzania, 2000-2014. POPULATION OR SAMPLE: Deliveries (n = 33 346). METHODS: HIV-positive women were compared with HIV-negative women during four periods spanning changing national guidelines. MAIN OUTCOME MEASURES: Known maternal HIV status, HIV treatment for woman, number of antenatal care (ANC) visits, routine folate/iron in pregnancy, anemia, delivery complications/interventions. RESULTS: We observed an increase in deliveries with known maternal HIV status and women receiving HIV treatment, and a decline in deliveries with positive maternal HIV status (p-values for trend <0.001). The proportion of women with less than four ANC visits increased to above 30 percent irrespective of HIV status. Use of routine folate/iron increased, corresponding to a decrease in anemia which was strongest in HIV-negative women. Incidence of elective caesarean section (CS) and emergency CS remained unchanged for HIV-positive women (7.1% and 25.5%, respectively, in the last period). Use of invasive procedures declined in both groups of women. Mothers who were young, single, had low education, high parity or lived in the rural area more often had indicators of poor antenatal care. CONCLUSIONS: Increasing adherence to national guidelines over time was found for most selected outcomes. Still, a high occurrence of insufficient ANC, anemia and emergency CS call for efforts to explore and identify barriers that hinder optimal care.