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.publishedVersio

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.publishedVersio

Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study - Fig 1

<p>Percentage of deliveries with known maternal HIV status (left panel). Percentage of deliveries with HIV-positive mother. Denominators are deliveries with known maternal HIV status (right panel).</p

Characteristics of pregnant women in Northern Tanzania by HIV status and time period.

<p>Characteristics of pregnant women in Northern Tanzania by HIV status and time period.</p

Antenatal factors and delivery characteristics among HIV-positive and HIV-negative pregnant women in Northern Tanzania by time period₁.

<p>Forest plot shows relative risks in each time period, HIV-positive women compared with HIV-negative women. (Adjusted for maternal age, marital status, parity, current residence and education level.) P-values in plot are for trends in ARR. ₁ Time periods: 2000–2003: Pilot phase before national PMTCT guidelines; 2004–2006: WHO 2004 guidelines; 2007–2011: Revised WHO 2004 guidelines; 2012–2014: WHO Option A guidelines. ₂ Missing observations: Referred for delivery (3.8%), anemia (38.7%). Other variables <2% missing observations.</p

Percentage and adjusted relative risk (ARR) of selected indicators of pregnancy care by maternal sociodemographic characteristics.

<p>Northern Tanzania (time period 4).</p