Use Of Antiretroviral Therapy In Pregnancy Research Articles

The impact of free antiretroviral therapy for pregnant non-citizens and their infants in Botswana.

In December 2019, the Botswana government expanded free antiretroviral therapy (ART) to include non-citizens. We evaluated the impact of this policy change on antenatal care (ANC), antiretroviral therapy coverage and adverse birth outcomes. The Tsepamo Surveillance study collects data at up to 18 delivery sites in Botswana. We compared outcomes in citizens and non-citizens living with HIV before and after antiretroviral therapy expansion to non-citizens. Adverse birth outcomes included preterm delivery (PTD) <37 weeks, very preterm delivery (VPTD) <32 weeks, small for gestational age (SGA) <10th percentile, very small for gestational age (VSGA) <3rd percentile, stillbirth and neonatal death. Log-binomial regression models were constructed to generate risk ratios. From August 2014 to September 2021, 45,576 (96.5%) citizens and 1513 (3.2%) non-citizens living with HIV delivered; 954 (62.9%) non-citizen deliveries were before the antiretroviral therapy expansion, and 562 (37.1%) were after. Non-citizen ANC attendance among pregnant people living with HIV increased from 79.2% pre-expansion to 87.2% post-expansion (p<0.001), and became more similar to citizens (96.0% post-expansion). Non-citizens receiving any antenatal antiretroviral therapy increased from 65.5% pre-expansion to 89.9% post-expansion (p < 0.001), also more similar to citizens (97.2% post-expansion). Infants born to non-citizens with singleton gestations in the pre-expansion period had significantly greater risk of PTD (aRR = 1.28, 95% CI, 1.11, 1.46), VPTD (aRR = 1.89, 95% CI, 1.43, 2.44) and neonatal death (aRR = 1.69, 95% CI, 1.03, 2.60), but reduced SGA risk (aRR = 0.75; 95% CI, 0.62, 0.89) compared with citizens. Post-expansion, greater declines in most adverse outcomes were observed in non-citizens, with largely similar outcomes between non-citizens and citizens. Non-significant differences were observed for non-citizenship in PTD (aRR = 0.84, 95% CI, 0.66, 1.06), VPTD (aRR = 0.57, 95% CI, 0.28, 1.01), SGA (aRR = 0.91, 95% CI, 0.72, 1.13), VSGA (aRR = 0.87, 95% CI, 0.58, 1.25), stillbirth (aRR = 0.71, 95% CI, 0.35, 1.27) and neonatal death (aRR = 1.35, 95% CI, 0.60, 2.62). Following the expansion of free antiretroviral therapy to non-citizens, gaps narrowed in ANC and antiretroviral therapy use in pregnancy between citizens and non-citizens living with HIV. Disparities in adverse birth outcomes were no longer observed.

Comparison of the Effects of Three Dual-Nucleos(t)ide Reverse Transcriptase Inhibitor Backbones on Placenta Mitochondria Toxicity and Oxidative Stress Using a Mouse Pregnancy Model.

Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the backbone of HIV antiretroviral therapy (ART). ART use in pregnancy has been associated with adverse birth outcomes, in part due to NRTI-induced mitochondrial toxicity. Direct comparison on the effects of commonly used dual-NRTI regimens on placental mitochondria toxicity in pregnancy is lacking. We compared zidovudine/lamivudine, abacavir/lamivudine, and tenofovir/emtricitabine using a mouse model and examined markers of placental mitochondrial function and oxidative stress. Zidovudine/lamivudine and abacavir/lamivudine were associated with lower fetal and placental weights compared to controls, whereas tenofovir/emtricitabine was associated with the least fetal and placental weight reduction, as well as lower resorption rates. Placental mitochondrial DNA content, as well as placental expression of cytochrome c-oxidase subunit-II, DNA polymerase gamma, and citrate synthase, was higher in tenofovir/emtricitabine-treated mice compared to other groups. Zidovudine/lamivudine-treated mice had elevated malondialdehyde levels (oxidative stress marker) compared to other groups and lower mRNA levels of manganese superoxide dismutase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in the placenta compared to tenofovir/emtricitabine-treated mice. We observed differences in effects between NRTI regimens on placental mitochondrial function and birth outcomes. Tenofovir/emtricitabine was associated with larger fetuses, increased mtDNA content, and higher expression of mitochondrial-specific antioxidant enzymes and mitochondrial biogenesis enzymes, whereas zidovudine/lamivudine was associated with markers of placental oxidative stress.

Use of antiretroviral therapy in pregnancy and association with birth outcome among women living with HIV in Denmark: A nationwide, population‐based cohort study

ObjectiveTo describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes.MethodsA population‐based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes.ResultsIn total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First‐trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23–11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13–9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes.ConclusionsPregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors.

Gender Differences in Clinical Outcomes among HIV-Positive Individuals on Antiretroviral Therapy in Canada: A Multisite Cohort Study

BackgroundCohort data examining differences by gender in clinical responses to combination antiretroviral therapy (ART) remain inconsistent and have yet to be explored in a multi-province Canadian setting. This study investigates gender differences by injection drug use (IDU) history in virologic responses to ART and mortality.MethodsData from the Canadian Observational Cohort (CANOC) collaboration, a multisite cohort study of HIV-positive individuals initiating ART after January 1, 2000, were included. This analysis was restricted to participants with a follow-up HIV-RNA plasma viral load measure and known IDU history. Weibull hazard regression evaluated time to virologic suppression (2 consecutive measures <50 copies/mL), rebound (>1000 copies/mL after suppression), and all-cause mortality. Sensitivity analyses explored the impact of presumed ART use in pregnancy on virologic outcomes.ResultsAt baseline, women (1120 of 5442 participants) were younger (median 36 vs. 41 years) and more frequently reported IDU history (43.5% vs. 28.8%) (both p<0.001). Irrespective of IDU history, in adjusted multivariable analyses women were significantly less likely to virologically suppress after ART initiation and were at increased risk of viral load rebound. In adjusted time to death analysis, no differences by gender were noted. After adjusting for presumed ART use in pregnancy, observed gender differences in time to virologic suppression for non-IDU, and time to virologic rebound for IDU, became insignificant.ConclusionsHIV-positive women in CANOC are at heightened risk for poor clinical outcomes. Further understanding of the intersections between gender and other factors augmenting risk is needed to maximize the benefits of ART.

British HIV Association guidelines for the management ofHIVinfection in pregnant women 2012

British HIV Association guidelines for the management of<scp>HIV</scp>infection in pregnant women 2012

Pharmacokinetic Considerations of Perinatal Antiretroviral Therapy

Antiretroviral therapy (ART) in pregnant women represents a unique combination of therapy and prophylaxis of HIV infection. Until the global epidemic of HIV and the discovery of efficient prevention of perinatal transmission through ART, the world has not witnessed a pharmacologic intervention of such a scale during pregnancy and delivery. The use of ART in pregnancy creates unique challenges in delivering therapeutic agents, targeting the HIV virus in both the pregnant woman and her unborn child, throughout dramatic changes in their physiologic state. With an increased complexity of perinatal ART and the introduction of novel agents into clinical practice, a better understanding of the pharmacokinetics (PK) and pharmacodynamics of ARV drugs is crucial for the safe and most effective use of ARV drugs in women during pregnancy and infants in the first months of life. While PK studies are already difficult to perform during pregnancy, they are particularly challenging in women with HIV infection due to multiple social, economic and cultural constrains. In this paper we provide an overview of published studies of ART disposition during pregnancy, labor, breastfeeding and in the newborn infant after delivery.

Strategies to prevent mother-to-child transmission of HIV

This review describes recent advances in the prevention of mother-to-child transmission, focusing on the use of antiretroviral treatment strategies in pregnancy, and discusses the emergence of viral resistance following the use of nevirapine to prevent mother-to-child transmission. Mother-to-child transmission has been dramatically reduced in developed countries by the use of antiretroviral treatment and avoidance of breastfeeding. Highly active antiretroviral therapy use in pregnancy is recommended for women who require ongoing treatment, and, where available, is also very effective in reducing mother-to-child transmission in women with higher CD4 counts. The addition of a maternal and infant nevirapine dose to antenatal zidovudine can reduce transmission to below 5%, approximately half the transmission rate that can be achieved by single-dose nevirapine alone. The emergence of resistant virus following nevirapine use is a concern, occurring in up to 60% of mothers and 50% of infants following a single dose. Addition of zidovudine and lamivudine for 4-7 days postpartum can reduce the risk of resistance to 10%. There is broad consensus on an approach to preventing mother-to-child transmission, which provides antiretroviral treatment in pregnancy and beyond to those women who need it, and an effective prophylactic regimen for those who do not yet need treatment, These regimens include highly active antiretroviral therapy, where available, a zidovudine-plus-nevirapine regimen in other settings, or nevirapine alone where this is all that is possible. More work is needed on the impact of nevirapine resistance and on reducing breast-milk transmission.

Guidelines for the management of HIV infection in pregnant women and the prevention of mother‐to‐child transmission of HIV

Aims of the guidelines These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of ‘best evidence’ the guidelines rely heavily on ‘expert opinion’. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.