Publications by authors named "Rebecca Zash"

40 Publications

Seasonality of adverse birth outcomes in women with and without HIV in a representative birth outcomes surveillance study in Botswana.

BMJ Open 2021 09 3;11(9):e045882. Epub 2021 Sep 3.

Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.

Introduction: Sub-Saharan Africa has the largest number of people with HIV, one of the most severe burdens of adverse birth outcomes globally and particular vulnerability to climate change. We examined associations between seasonality and adverse birth outcomes among women with and without HIV in a large geographically representative birth outcomes surveillance study in Botswana from 2015 to 2018.

Methods: We evaluated stillbirth, preterm delivery, very preterm delivery, small for gestational age (SGA), very SGA, and combined endpoints of any adverse or severe birth outcome. We estimated the risk of each outcome by month and year of delivery, and adjusted risks ratios (ARRs) of outcomes during the early wet (1 November-15 January), late wet (16 January-31 March) and early dry (1 April-15 July) seasons, compared with the late dry (16 July-31 October) season. Analyses were conducted overall and separately by HIV status.

Results: Among 73 178 women (24% with HIV), the risk of all adverse birth outcomes peaked in November-January and reached low points in September. Compared with the late dry season, the ARRs for any adverse birth outcome were 1.03 (95% CI 1.00 to 1.06) for the early dry season, 1.08 (95% CI 1.04 to 1.11) for the early wet season and 1.07 (95% CI 1.03 to 1.10) for the late wet season. Comparing the early wet season to the late dry season, we found that ARRs for stillbirth and very preterm delivery were higher in women with HIV (1.23, 95% CI 0.96 to 1.59, and 1.33, 95% CI 1.10 to 1.62, respectively) than in women without HIV (1.07, 95% CI 0.91 to 1.26, and 1.19, 95% CI 1.04 to 1.36, respectively).

Conclusions: We identified a modest association between seasonality and adverse birth outcomes in Botswana, which was greatest among women with HIV. Understanding seasonal patterns of adverse birth outcomes and the role of HIV status may allow for mitigation of their impact in the face of seasonal extremes related to climate change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-045882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420660PMC
September 2021

The Impact of Syndromic Management of Vaginal Discharge Syndrome on Adverse Birth Outcomes in Botswana.

Open Forum Infect Dis 2021 Aug 9;8(8):ofab366. Epub 2021 Jul 9.

Botswana-Harvard AIDS Initiative Partnership for HIV Research and Education, Gaborone, Botswana.

Background: Vaginal discharge syndrome (VDS) is a common clinical diagnosis during pregnancy in Botswana; it is treated with broad-spectrum antibiotics using a syndromic approach. We evaluated associations between the syndromic management of VDS and adverse birth outcomes.

Methods: The Tsepamo Study performs birth outcomes surveillance at government hospitals throughout Botswana. Obstetric record data collected from August 2014 to March 2019 were analyzed. Chi-square tests were conducted to compare proportions of maternal characteristics and infant outcomes. To avoid immortal time bias, all analyses were conducted among women who presented to care before 24 weeks gestation, with VDS categorized as present or absent by 24 weeks gestation. Log-binomial regression models were generated to determine associations between treated VDS and infant outcomes.

Results: VDS was diagnosed in 36 731 (30.7%) pregnant women, of whom 33 328 (90.7%) received antibiotics. Adjusted analyses yielded a harmful association between treated VDS and very preterm delivery (adjusted risk ratio, 1.11; 95% CI, 1.02-1.21). This association remained when restricting to women with VDS who received the recommended antibiotic treatment regimen. Sensitivity analyses produced nonsignificant associations when women with treated VDS were compared with women without VDS who received antibiotics for other indications.

Conclusions: A clinical diagnosis of VDS is common among pregnant women in Botswana, and the majority receive antibiotics in pregnancy. Although analyses of VDS occurring later in pregnancy are precluded by immortal time bias, a modest association between treated VDS and very preterm delivery was observed among women diagnosed with VDS by 24 weeks gestation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofab366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351807PMC
August 2021

Editorial: Viral infections at the maternal-fetal interface - setting the research agenda.

J Infect Dis 2021 Jul 22. Epub 2021 Jul 22.

Beth Israel Deaconess Medical Center Division of Infectious Diseases, Harvard Medical School.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiab356DOI Listing
July 2021

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

Int J Gynaecol Obstet 2021 Jul 1. Epub 2021 Jul 1.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Objective: The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries.

Methods: We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159 mm Hg systolic or 90-109 mm Hg diastolic blood pressure) after 20 weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis.

Results: We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83).

Conclusion: Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.13809DOI Listing
July 2021

Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana.

J Int AIDS Soc 2021 Jun;24(6):e25763

Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.

Introduction: Antiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART-associated weight gain on pregnancy outcomes among women living with HIV.

Methods: Using data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)).

Results: Of 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks' gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre-pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata.

Conclusions: ART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight-based ART treatment strategies improve maternal and child health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jia2.25763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236225PMC
June 2021

Limited surface examination to evaluate potential teratogens in a resource-limited setting.

Birth Defects Res 2021 05 28;113(9):702-707. Epub 2021 Mar 28.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: To determine the frequency of malformations that would be identified in the limited surface examination of a newborn by the delivering nurse midwife in a resource-limited setting.

Methods: The limited surface examination will identify visible external anomalies, but not abnormalities inside the mouth, most heart defects, undescended testes, inguinal hernias, hip dysplasia, peripheral vascular anomalies, and some internal anomalies. The findings in a malformations surveillance program, involving 289,365 births in Boston, have been used to establish the prevalence rate of malformations that would be identified and not identified. In African countries, the number of anomalies to be identified should also be reduced by excluding polydactyly, postaxial, type B, a common minor finding, from the list of potential malformations.

Results: Of note, 2.05% (n = 5,941) of the 289,365 births surveyed had one or more malformations. The abnormalities that would have been missed, using surface exam alone, accounted for 0.5% of all of malformations identified and reduced the overall prevalence rate of malformations to 1.5%. In addition, excluding all infants with isolated postaxial polydactyly, type B reduced the expected prevalence rate of malformations to 1.3% in unexposed newborn infants.

Conclusion: A limited surface examination can detect the majority of malformations among newborn infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bdr2.1887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148051PMC
May 2021

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19.

JAMA 2021 04;325(15):1535-1544

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines.

Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses.

Design, Setting, And Participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S.

Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group).

Main Outcomes And Measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses.

Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced.

Conclusion And Relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

Trial Registration: ClinicalTrials.gov Identifier: NCT04436276.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2021.3645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953339PMC
April 2021

Weight gain during pregnancy among women initiating dolutegravir in Botswana.

EClinicalMedicine 2020 Dec 5;29-30:100615. Epub 2020 Nov 5.

Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.

Background: Recent data suggests clinically significant weight gain among non-pregnant HIV-positive adults after starting dolutegravir-based ART (DTG). Excess or insufficient weight gain in pregnancy could adversely impact pregnancy outcomes, but data for pregnant women receiving DTG are limited.

Methods: The Tsepamo Study captured data at delivery sites in Botswana from 2014 to 2019. HIV testing, HIV treatment information, and weight measurements during antenatal care were abstracted from the maternity obstetric record at delivery. HIV-positive women initiating DTG or efavirenz-based ART (EFV) between conception and 17 weeks gestation and HIV-uninfected women first presenting for antenatal care before 17 weeks gestation were included. We evaluated weekly weight gain, total 18-week weight gain, excess weight gain (>0.59 kg/week), insufficient weight gain (<0.18 kg/week), and weight loss between 18±2 and 36±2 weeks gestation, adjusting for demographic and clinical variables.

Findings: Baseline characteristics were similar by exposure group, including pre-pregnancy and early pregnancy weight. Compared with EFV, mean weekly weight gain between 18 and 36 weeks gestation was 0.05 (95% CI 0.03, 0.07) kg/week higher for women initiating DTG and 0.12 (0.10, 0.14) kg/week higher for HIV-uninfected women. Mean 18-week weight gain was 1.05 (95% CI 0.61, 1.49) kg higher for women initiating DTG and 2.31 (1.85, 2.77) kg higher for HIV-uninfected women, compared with EFV. Women initiating DTG were more likely to gain excess weight but less likely to gain insufficient weight or lose weight than women initiating EFV.

Interpretation: Women initiating DTG compared with EFV during pregnancy gained more weight between 18 and 36 weeks gestation. Neither group gained as much weight as HIV-uninfected women. Initiating DTG compared with EFV during pregnancy could increase the risk of excess weight gain but decrease the risk of insufficient weight gain and weight loss, which could have positive and negative consequences in pregnancy. Our findings are consistent with prior studies in non-pregnant adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788432PMC
December 2020

Modest reduction in adverse birth outcomes following the COVID-19 lockdown.

Am J Obstet Gynecol 2021 06 24;224(6):615.e1-615.e12. Epub 2020 Dec 24.

Harvard T.H. Chan School of Public Health, Boston, MA; Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.

Background: Widespread lockdowns imposed during the coronavirus disease 2019 crisis may impact birth outcomes.

Objective: This study aimed to evaluate the association between the COVID-19 lockdown and the risk of adverse birth outcomes in Botswana.

Study Design: In response to the coronavirus disease 2019 crisis, Botswana enforced a lockdown that restricted movement within the country. We used data from an ongoing nationwide birth outcomes surveillance study to evaluate adverse outcomes (stillbirth, preterm birth, small-for-gestational-age fetuses, and neonatal death) and severe adverse outcomes (stillbirth, very preterm birth, very-small-for-gestational-age fetuses, and neonatal death) recorded prelockdown (January 1, 2020-April 2, 2020), during lockdown (April 3, 2020-May 7, 2020), and postlockdown (May 8, 2020-July 20, 2020). Using difference-in-differences analyses, we compared the net change in each outcome from the prelockdown to lockdown periods in 2020 relative to the same 2 periods in 2017-2019 with the net change in each outcome from the prelockdown to postlockdown periods in 2020 relative to the same 2 periods in 2017-2019.

Results: In this study, 68,448 women delivered a singleton infant in 2017-2020 between January 1 and July 20 and were included in our analysis (mean [interquartile range] age of mothers, 26 [22-32] years). Across the included calendar years and periods, the risk of any adverse outcome ranged from 27.92% to 31.70%, and the risk of any severe adverse outcome ranged from 8.40% to 11.38%. The lockdown period was associated with a 0.81 percentage point reduction (95% confidence interval, -2.95% to 1.30%) in the risk of any adverse outcome (3% relative reduction) and a 0.02 percentage point reduction (95% confidence interval, -0.79% to 0.75%) in the risk of any severe adverse outcome (0% relative reduction). The postlockdown period was associated with a 1.72 percentage point reduction (95% confidence, -3.42% to 0.02%) in the risk of any adverse outcome (5% relative reduction) and a 1.62 percentage point reduction (95% confidence interval, -2.69% to -0.55%) in the risk of any severe adverse outcome (14% relative reduction). Reductions in adverse outcomes were largest among women with human immunodeficiency virus and among women delivering at urban delivery sites, driven primarily by reductions in preterm birth and small-for-gestational-age fetuses.

Conclusion: Adverse birth outcomes decreased from the prelockdown to postlockdown periods in 2020, relative to the change during the same periods in 2017-2019. Our findings may provide insights into associations between mobility and birth outcomes in Botswana and other low- and middle-income countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2020.12.1198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817370PMC
June 2021

Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis.

EClinicalMedicine 2020 Nov 16;28:100573. Epub 2020 Oct 16.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral therapy (ART) regimens.

Methods: We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework.

Findings: We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio [OR]: 1·94; 95% credible interval [CrI]: 1·48-2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04-0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48-0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50-0·92).

Interpretation: The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable.

Funding: WHO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700905PMC
November 2020

Compassionate Use of Remdesivir in Pregnant Women with Severe Covid-19.

Clin Infect Dis 2020 Oct 8. Epub 2020 Oct 8.

Rutgers New Jersey Medical School, Newark, NJ, United States.

Background: Remdesivir is efficacious for severe COVID-19 in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir.

Methods: Reported data span March 21 to June 16, 2020 for hospitalized pregnant women with PCR-confirmed SARS-CoV-2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200mg on Day 1, followed by 100mg for Days 2-10, given intravenously).

Results: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day=1; range 0-3). At baseline, 40% of pregnant women (median gestational age 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By Day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to pregnancy and underlying disease; most laboratory abnormalities were Grades 1 or 2. There was one maternal death attributed to underlying disease and no neonatal deaths.

Conclusions: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate use remdesivir, recovery rates were high, with a low rate of serious adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797739PMC
October 2020

A Systematic Review of Treatment and Outcomes of Pregnant Women With COVID-19-A Call for Clinical Trials.

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa350. Epub 2020 Aug 13.

Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre, Montreal, Québec, Canada.

Background: Data pertaining to COVID-19 in pregnancy are limited; to better inform clinicians, we collated data from COVID-19 cases during pregnancy and summarized clinical trials enrolling this population.

Methods: We performed a systematic literature review of PubMed/MEDLINE to identify cases of COVID-19 in pregnancy or the postpartum period and associated outcomes. We then evaluated the proportion of COVID-19 clinical trials (from ClinicalTrials.gov) excluding pregnant or breastfeeding persons (both through June 29, 2020).

Results: We identified 11 308 published cases of COVID-19 during pregnancy. Of those reporting disease severity, 21% (416/1999) were severe/critical. Maternal and neonatal survival were reassuring (98% [10 437/10 597] and 99% [1155/1163], respectively). Neonatal disease was rare, with only 41 possible cases of infection reported in the literature. Of 2351 ongoing COVID-19 therapeutic clinical trials, 1282 were enrolling persons of reproductive age and 65% (829/1282) excluded pregnant persons. Pregnancy was an exclusion criterion for 69% (75/109) of chloroquine/hydroxychloroquine, 80% (28/35) of lopinavir/ritonavir, and 48% (44/91) of convalescent plasma studies. We identified 48 actively recruiting or completed drug trials reporting inclusion of this population.

Conclusions: There are limited published reports of COVID-19 in pregnancy despite more than 14 million cases worldwide. To date, clinical outcomes appear reassuring, but data related to important long-term outcomes are missing or not yet reported. The large number of clinical trials excluding pregnant persons, despite interventions with safety data in pregnancy, is concerning. In addition to observational cohort studies, pregnancy-specific adaptive clinical trials could be designed to identify safe and effective treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454907PMC
September 2020

Adverse Birth Outcomes in Botswana Among Women With Vertically or Horizontally Acquired Human Immunodeficiency Virus.

J Pediatric Infect Dis Soc 2021 Apr;10(3):252-258

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Background: Women with vertically acquired HIV (VHIV) may have a greater risk of adverse birth outcomes than women with horizontally acquired HIV (HHIV).

Methods: The Tsepamo study performed birth outcomes surveillance at 8 government delivery sites in Botswana from July 2014 through March 2019. Pregnant women diagnosed with HIV before their 11th birthday received VHIV status, and other women had HHIV. Small for gestational age (SGA), preterm delivery (PTD), stillbirth, and neonatal death were compared using χ2 and Fisher's exact tests. Log-binomial regression models determined risk ratios (RRs).

Results: VHIV women (n = 402) aged 15-27 years were identified over 4 years of surveillance and compared with HHIV women (n = 8465) of the same age. VHIV women were more likely to use nevirapine (NVP)-based antiretroviral treatment (ART) in pregnancy and to have SGA and very SGA infants, but less likely to have very PTD infants. In unadjusted analyses, VHIV women had a higher risk of any adverse birth outcome combined (RR = 1.21, 95% confidence interval [CI], 1.08-1.36). After adjusting for potential confounders, particularly use of NVP-based regimens, the risk of adverse birth outcomes among VHIV and HHIV women was similar.

Conclusions: NVP-based ART is a primary and modifiable risk factor for adverse birth outcomes. Updating ART regimens could improve birth outcomes for women with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023308PMC
April 2021

Lymphopenia and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Hospitalized Obstetric Patients.

Obstet Gynecol 2020 08;136(2):229-231

Departments of Obstetrics and Gynecology and Anesthesia, Critical Care and Pain Medicine, and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000003984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874502PMC
August 2020

Mother-to-Child HIV Transmission With In Utero Dolutegravir vs. Efavirenz in Botswana.

J Acquir Immune Defic Syndr 2020 07;84(3):235-241

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Background: A large-scale evaluation of mother-to-child transmission (MTCT) with dolutegravir (DTG)-based antiretroviral treatment (ART) has not been conducted previously.

Setting: Botswana was the first African country to change from efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC) to DTG/TDF/FTC first-line ART.

Methods: From April 2015 to July 2018, the Early Infant Treatment Study offered HIV DNA testing at <96 hours of life. Maternal ART regimen was available for screened infants who could be linked to the separate Tsepamo surveillance study database. We evaluated characteristics of HIV-positive infants, and compared MTCT rates by ART regimen for linked infants.

Results: Of 10,622 HIV-exposed infants screened, 42 (0.40%) were HIV-positive. In total, 5064 screened infants could be linked to the surveillance database, including 1235 (24.4%) exposed to DTG/TDF/FTC and 2411 (47.6%) exposed to EFV/TDF/FTC. MTCT was rare when either regimen was started before conception: 0/213 [0.00%, 95% confidence interval (CI): 0.00% to 1.72%] on DTG, 1/1497 (0.07%, 95% CI: 0.00% to 0.37%) on EFV. MTCT was similar for women starting each ART regimen in pregnancy: 8/999 (0.80%, 95% CI: 0.35% to 1.57%) for DTG and 8/883 (0.91%, 95% CI: 0.39% to 1.78%) for EFV (risk difference 0.11%, 95% CI: -0.79% to 1.06%). Most MTCT events (4/8 with DTG, 6/9 with EFV) occurred when ART was started <90 days before delivery. Infants exposed to DTG in utero had lower baseline HIV RNA compared with other HIV-infected infants.

Conclusion: In utero MTCT in Botswana remains rare in the DTG era. No significant MTCT differences were observed between DTG/TDF/FTC and EFV/TDF/FTC. Risk was highest for both groups when ART was started in the third trimester.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293566PMC
July 2020

Mid-trimester cervical length not associated with HIV status among pregnant women in Botswana.

PLoS One 2020 11;15(3):e0229500. Epub 2020 Mar 11.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, United States of America.

Objective: HIV-infected women on antiretroviral therapy have a higher risk of preterm birth than HIV-uninfected women in Botswana. To better understand the mechanism for preterm birth among HIV-infected women, we evaluated whether mid-trimester cervical length differed by HIV status as cervical shortening is associated with an increased risk for preterm birth.

Methods: We conducted a prospective cohort study among pregnant women receiving care at the Scottish Livingstone Hospital in Molepolole, Botswana. Consecutive women referred for routine obstetrical ultrasound were consented and enrolled if between 22w0d and 24w6d by ultrasound biometry. Blinded to maternal HIV status, an obstetrician measured transvaginal cervical length using standardized criteria. Cervical length, as well as the proportion of women with a short cervix (<25mm), were compared among HIV-infected and HIV-uninfected women. The acceptability of transvaginal ultrasound was also evaluated.

Results: Between April 2016 and April 2017, 853 women presenting for obstetric ultrasound were screened, 187 (22%) met eligibility criteria, and 179 (96%) were enrolled. Of those enrolled, 50 (28%) were HIV-infected (86% on antiretroviral therapy), 127 (71%) were HIV-uninfected, and 2 (1%) had unknown HIV status. There was no significant difference in mean cervical length between HIV-infected and HIV-uninfected women (32mm vs 31mm, p = 0.21), or in the proportion with a short cervix (10% vs 14%, p = 0.44). Acceptability data was available for 115 women who underwent a transvaginal ultrasound exam. Of these, 112 of 115 (97%) women deemed the transvaginal scan acceptable.

Conclusions: The increased risk of preterm birth observed among HIV-infected women receiving antiretroviral therapy in Botswana is unlikely associated with mid-trimester cervical shortening. Further research is needed to understand the underlying mechanism for preterm birth among HIV-infected women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229500PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065819PMC
July 2020

Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana.

N Engl J Med 2019 08 22;381(9):827-840. Epub 2019 Jul 22.

From the Division of Infectious Diseases, Beth Israel Deaconess Medical Center (R.Z., R.L.S.), the Department of Immunology and Infectious Diseases (R.Z., M.E., S.L., J. Makhema, R.L.S.) and the Center for Biostatistics in AIDS Research (D.L.J., S.B.), Harvard T.H. Chan School of Public Health, MassGeneral Hospital for Children, Massachusetts General Hospital (L.H.), and the Division of Infectious Diseases, Brigham and Women's Hospital (S.L.) - all in Boston; the Botswana-Harvard AIDS Institute Partnership (R.Z., M.D., G.M., A.I., S.D., J. Mabuta, M.M., T.G., M.E., S.L., J. Makhema, R.L.S.) and the University of Botswana Faculty of Medicine (T.G.), Gaborone, Botswana; and the University of Pennsylvania Perelman School of Medicine, Philadelphia (S.D.).

Background: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies.

Methods: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals.

Results: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87).

Conclusions: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1905230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995896PMC
August 2019

Brief Report: High Rates of Adverse Birth Outcomes in HIV and Syphilis Coinfected Women in Botswana.

J Acquir Immune Defic Syndr 2019 08;81(5):e135-e140

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Background: Little is known about the combined impact of HIV/syphilis coinfection on birth outcomes.

Methods: Antenatal HIV and syphilis test results, obstetric history, and infant birth outcomes were collected from obstetric records in maternity wards in Botswana between 2008 and 2011 (5 sites) and 2014 and 2016 (8 sites). We used logistic regression to compare adverse birth outcomes by HIV and syphilis status. Outcomes included stillbirth, preterm delivery, low birth weight, and in-hospital neonatal death.

Results: Of 76,466 women, 75,770 (99.1%) had HIV test results, and 20,520 (27.1%) were HIV positive. Syphilis test results were available for 67,290 (88.0%), and 697 (1.0%) had reactive rapid plasma reagin. Among 692 women with syphilis and an HIV test result, 261 (37.7%) were coinfected. HIV-infected women were more likely to be infected with syphilis than HIV-uninfected women [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.44 to 1.96]. From 2008-2011 to 2014-2016, the proportion of women with syphilis remained constant (1.1% vs. 1.0%, P = 0.41), but HIV/syphilis coinfection declined from 45% to 27% (P < 0.0001). Stillbirth occurred in 5.8% of coinfected women, compared with 1.9% with no HIV/syphilis (OR = 3.09; 95% CI: 1.83 to 5.23); 3.4% with HIV alone (OR = 1.75; 95% CI: 1.03 to 2.97), or 3.7% with syphilis alone (OR = 1.58; 95% CI: 0.77 to 3.25). Low birth weight occurred in 24.1% of coinfected women, compared with 12.1% with no HIV/syphilis (OR 2.31; 95% CI: 1.74 to 3.08; 20% with HIV alone (OR = 1.27; 95% CI: 0.96 to 1.69); or 14.6% with syphilis alone (OR = 1.85; 95% CI: 1.26 to 2.74).

Conclusions: Although HIV/syphilis coinfection in pregnancy has declined in the past decade, coinfection was associated with adverse birth outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636337PMC
August 2019

Methodological Challenges When Studying Distance to Care as an Exposure in Health Research.

Am J Epidemiol 2019 09;188(9):1674-1681

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwz121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735874PMC
September 2019

Audit of Early Mortality among Patients Admitted to the General Medical Ward at a District Hospital in Botswana.

Ann Glob Health 2019 03 4;85(1). Epub 2019 Mar 4.

Beth Israel Deaconess Medical Center, Boston, MA, US.

Background: Mortality among adult general medical admissions has been reported to be high across sub-Saharan Africa, yet there is a paucity of literature on causes of general medical inpatient mortality and quality-related factors that may contribute to the high incidence of deaths. Based on a prior study at our hospital as well as our clinical experience, death early in the hospitalization is common among patients admitted to the adult medical wards.

Objective: Quantify early inpatient mortality and identify factors contributing to early in-hospital mortality of medical patients in a resource-limited hospital setting in Botswana.

Methods: Twenty-seven cases of patients who died within 48 hours of admission to the general medical wards at Scottish Livingstone Hospital in Molepolole, Botswana from December 1, 2015-April 25, 2016 were retrospectively reviewed through a modified root cause analysis.

Findings: Early in-hospital mortality was most frequently attributed to septic shock, identified in 20 (74%) of 27 cases. The most common care management problems were delay in administration of antibiotics (15, 56%), inappropriate fluid management (15, 56%), and deficient coordination of care (15, 56%). The most common contributing factors were inadequate provider knowledge and skills in 25 cases (93%), high complexity of presenting condition in 20 (74%), and inadequate communication between team members in 18 (67%).

Conclusions: Poor patient outcomes in low-and middle-income countries like Botswana are often attributed to resource limitations. Our findings suggest that while early in-hospital mortality in such settings is associated with severe presenting conditions like septic shock, primary contributors to lack of better outcomes may be healthcare-provider and system-factors rather than lack of diagnostic and therapeutic resources. Low-cost interventions to improve knowledge, skills and communication through a focus on provider education and process improvement may provide the key to reducing early in-hospital mortality and improving hospitalization outcomes in this setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5334/aogh.1354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997521PMC
March 2019

Methodological Considerations in Evaluating Pregnancy Outcomes in Women Living With HIV.

J Acquir Immune Defic Syndr 2019 06;81(2):e63-e64

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522271PMC
June 2019

Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception.

N Engl J Med 2018 09 24;379(10):979-981. Epub 2018 Jul 24.

Harvard T.H. Chan School of Public Health, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc1807653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550482PMC
September 2018

HIV treatment in pregnancy.

Lancet HIV 2018 08 26;5(8):e457-e467. Epub 2018 Jun 26.

Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, UK. Electronic address:

Almost 25 years since antiretroviral therapy (ART) was first shown to prevent mother-to-child transmission of HIV, 76% of pregnant women living with HIV (over 1 million women) receive ART annually. This number is the result of successes in universal ART scale-up in low-income and middle-income countries. Despite unprecedented ART-related benefits to maternal and child health, challenges remain related to ART adherence, retention in care, and unequal access to ART. Implementation research is ongoing to understand and to address obstacles that lead to loss to follow-up. The biological mechanisms that underlie observed associations between antenatal ART and adverse outcomes in pregnancy and birth are not completely understood, with further research needed as well as strengthening of the systems to assess safety of antiretroviral drugs for the mother and HIV-exposed child. In the treat-all era, as duration of treatment and options for ART expand, pregnant women will remain a priority population for treatment optimisation to promote their health and that of their ART-exposed children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(18)30059-6DOI Listing
August 2018

Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study.

Lancet Glob Health 2018 07 4;6(7):e804-e810. Epub 2018 Jun 4.

Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Global rollout of dolutegravir-based antiretroviral therapy (ART) has been hampered in part by insufficient safety data in pregnancy. We compared birth outcomes among women initiating dolutegravir-based ART with those among women initiating efavirenz-based ART in pregnancy in Botswana.

Methods: In this observational study, we captured birth outcome data at eight government hospitals throughout Botswana (~45% of all deliveries in the country) in an ongoing study that started on Aug 15, 2014. In 2016, Botswana changed first-line ART from efavirenz-tenofovir-emtricitabine to dolutegravir-tenofovir-emtricitabine, including for pregnant women. This analysis includes women starting either efavirenz-based ART or dolutegravir-based ART during singleton pregnancy (regimen started and delivery occurring between Aug 15, 2014, and Aug 15, 2016, for efavirenz-based ART and between Nov 1, 2016, and Sept 30, 2017, for dolutegravir-based ART). We excluded births to mothers who had switched regimen or stopped ART. The primary outcomes were the combined endpoints of any adverse outcome (stillbirth, preterm birth [<37 weeks' gestation], small for gestational age [SGA; less than the tenth percentile of birthweight by gestational age], or neonatal death [within 28 days of age]) and severe adverse outcomes (stillbirth, neonatal death, very preterm birth [<32 weeks' gestation], and very SGA [less than the third percentile of birthweight by gestational age]). We fitted log-binomial regression models, controlling for maternal age, gravidity, and education, to estimate adjusted risk ratios (aRRs).

Findings: Our analysis included 1729 pregnant women who initiated dolutegravir-based ART and 4593 who initiated efavirenz-based ART. The risk for any adverse birth outcome among women on dolutegravir versus efavirenz was similar (33·2% vs 35·0%; aRR 0·95, 95% CI 0·88-1·03), as was the risk of any severe birth outcome (10·7% vs 11·3%; 0·94, 0·81-1·11). We found no significant differences by regimen in the individual outcomes of stillbirth, neonatal death, preterm birth, very preterm birth, SGA, or very SGA.

Interpretation: Adverse birth outcomes were similar among pregnant women who initiated dolutegravir-based and efavirenz-based ART. Dolutegravir-based ART can be safely initiated in pregnancy.

Funding: National Institutes of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2214-109X(18)30218-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071315PMC
July 2018

Effect of Gestational Age at Tenofovir-Emtricitabine-Efavirenz Initiation on Adverse Birth Outcomes in Botswana.

J Pediatric Infect Dis Soc 2018 Aug;7(3):e148-e151

Division of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, Massachusetts.

Among human immunodeficiency virus-positive women in Botswana on the recommended first-line antiretroviral therapy regimen, tenofovir-emtricitabine-efavirenz, initiated within the first or early second trimester, we found no increased risk of stillbirth, neonatal death, preterm/very preterm delivery, or the infant being born small or very small for gestational age. Treatment with tenofovir-emtricitabine-efavirenz <1 year before conception increased the risk of preterm delivery slightly over late-second-trimester treatment initiation (adjusted risk ratio, 1.33 [95% confidence interval, 1.04-1.70]).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piy006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097579PMC
August 2018

Safety and pharmacokinetics of dolutegravir in HIV-positive pregnant women: a systematic review.

J Virus Erad 2018 Apr 1;4(2):66-71. Epub 2018 Apr 1.

Beth Israel Deaconess Medical Center, Division of Infectious Diseases, Boston, USA.

Background: The integrase strand transfer inhibitor dolutegravir (DTG) is being introduced into low- and middle-income countries (LMICs) as an alternative to first-line treatment with non-nucleoside reverse transcriptase inhibitors. However, DTG is not yet widely recommended for use in pregnant women. The aim of this systematic review was to analyse all available data on birth outcomes and congenital anomalies in the infants of pregnant women treated with DTG.

Methods: A PubMed and Embase search was conducted using the terms "dolutegravir" or "DTG" and "pregnancy" or "pregnant" from the earliest available date on the database to 26 July 2017. Any reports involving women who were pregnant, HIV positive and taking DTG were included. The percentage of pregnant women with adverse birth outcomes or congenital anomalies in their infants after taking dolutegravir was compared with five historical control databases.

Results: There were six databases included in the main analysis of birth outcomes and congenital anomalies, with a total of 1200 pregnant women. The percentage of pregnant women taking DTG with adverse birth outcomes and congenital abnormalities was similar to results from historical control studies of HIV-positive women. However, there was significant heterogeneity among the six databases - the percentage of infants with congenital anomalies ranged from 0.0% in Botswana (0/116 infants) to 13.3% in IMPAACT P1026S (2/15 infants).

Conclusions: Up to 15 million people could be on treatment with DTG in LMICs within the next 5 years, of whom a substantial percentage is likely to be women of child-bearing potential. In many countries with large HIV epidemics, unplanned pregnancies are common and access to antenatal clinic facilities may be limited. Continued pharmacovigilance is essential, but it is reassuring that no clear safety signals have been detected, to date, for pregnant women treated with DTG in terms of birth outcomes or congenital anomalies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892677PMC
April 2018

What is the risk of major congenital abnormalities among women on antiretroviral therapy?

AIDS 2018 01;32(3):403-404

Medical Genetics Unit, MassGeneral Hospital for Children, Department of Pediatrics, Boston, Massachusetts, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000001711DOI Listing
January 2018

Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes.

AIDS 2018 Jan;32(1):113-120

Division of Infectious Disease, Beth Israel Deaconess Medical Center.

Objective: To compare the effect of preconception initiation of zidovudine, lamivudine, nevirapine (ZDV/3TC/NVP) versus tenofovir, emtricitabine, efavirenz (TDF/FTC/EFV) on adverse birth outcomes.

Design: Emulation of a hypothetical (target) trial using a birth surveillance study in Botswana during an era of CD4-based antiretroviral therapy (ART) initiation.

Methods: In women who initiated ART less than 3 years from HIV diagnosis, conceived 0.5-5 years after ART initiation, and delivered at least 24-week gestation, we estimated risk ratios for stillbirth, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), small-for-gestational-age (SGA) (<10 percentile), very SGA (<3 percentile), and any adverse or severe birth outcome for first-line ZDV/3TC/NVP versus TDF/FTC/EFV. We conducted a historical comparison in women who initiated TDF/FTC/EFV in 2012-2015 and ZDV/3TC/NVP in 2004-2011, and a contemporaneous comparison in an era of overlapping use from 2009 to 2013.

Results: In the historical comparison, 1108 women initiated TDF/FTC/EFV and 637 initiated ZDV/3TC/NVP. In the contemporaneous comparison, 1052 initiated TDF/FTC/EFV and 298 initiated ZDV/3TC/NVP. TDF/FTC/EFV initiators were younger and more likely to be nulliparous than ZDV/3TC/NVP initiators in both comparisons. In the historical comparison, the adjusted risk ratios (95% confidence interval) comparing ZDV/3TC/NVP with TDF/FTC/EFV were 2.95 (1.76, 4.96) for stillbirth, 1.40 (1.17, 1.67) for preterm delivery, 2.58 (1.70, 3.91) for very preterm delivery, 1.96 (1.64, 2.34) for SGA, 2.32 (1.73, 3.09) for very SGA, 1.54 (1.38, 1.72) for any adverse birth outcome, and 2.20 (1.76, 2.75) for any severe birth outcome, and were similar in the contemporaneous comparison.

Conclusion: Preconception initiation of ZDV/3TC/NVP compared with TDF/FTC/EFV may increase the risk of adverse birth outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000001673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718935PMC
January 2018

Comparative Safety of Antiretroviral Treatment Regimens in Pregnancy.

JAMA Pediatr 2017 10 2;171(10):e172222. Epub 2017 Oct 2.

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Importance: Maternal antiretroviral treatment (ART) started before conception may increase the risk for adverse birth outcomes among women with human immunodeficiency virus (HIV) infection, but whether the risk differs by ART regimen is unknown.

Objective: To compare the risk for selected birth outcomes by maternal ART regimen.

Design, Setting, And Participants: This observational birth outcomes surveillance study compared all live births and stillbirths with a gestational age of at least 24 weeks in 8 geographically dispersed government hospitals throughout Botswana (approximately 45% of births nationwide). Data were collected from August 15, 2014, through August 15, 2016.

Exposures: Births among HIV-infected women who started 3-drug ART regimens before their last menstrual period and did not switch or stop ART in pregnancy were considered to be ART exposed from conception.

Main Outcomes And Measures: The primary outcomes were any adverse birth outcome, including stillbirth, preterm birth (<37 weeks), small size for gestational age (SGA; <10th percentile of weight for gestational age) or neonatal death (<28 days from delivery), and any severe adverse outcome, including very preterm birth (<32 weeks), very SGA (<3rd percentile of weight for gestational age), stillbirth, and neonatal death.

Results: Information was available for 47 027 of 47 124 births (99.8%) at surveillance maternity hospitals (mean [SD] age of mothers, 26.86 [6.45] years). Among 11 932 HIV-exposed infants, 5780 (48.4%) were ART exposed from conception. Adverse birth outcomes were more common among HIV-exposed infants than HIV-unexposed infants (39.6% vs 28.9%; adjusted relative risk [ARR], 1.40; 95% CI, 1.36-1.44). The risk for any adverse birth outcome was lower among infants exposed from conception to tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TDF-FTC-EFV) (901 of 2472 [36.4%]) compared with TDF-FTC and nevirapine (NVP) (317 of 760 [41.7%]; ARR, 1.15; 95% CI, 1.04-1.27); TDF-FTC and lopinavir-ritonavir (TDF-FTC-LPV-R) (112 of 231 [48.5%]; ARR, 1.31; 95% CI, 1.13-1.52); zidovudine, lamivudine, and NPV (ZDV-3TC-NVP) (647 of 1365 [47.4%]; ARR, 1.30; 95% CI, 1.20-1.41); or ZDV-3TC-LPV-R (75 of 167 [44.9%]; ARR, 1.21; 95% CI, 1.01-1.45). The risk for any severe adverse outcome was also lower among infants exposed from conception to TDF-FTC-EFV (303 of 2472 [12.3%]) compared with TDF-FTC-NVP (136 of 760 [17.9%]; ARR, 1.44; 95% CI, 1.19-1.74), TDF-FTC-LPV-R (45 of 231 [19.5%]; ARR, 1.58; 95% CI, 1.19-2.11), ZDV-3TC-NVP (283 of 1365 [20.7%]; ARR, 1.68; 95% CI, 1.44-1.96), or ZDV-3TC-LPV-R (39 of 167 [23.4%]; ARR, 1.93; 95% CI, 1.43-2.60) from conception. Compared with TDF-FTC-EFV, all other regimens were associated with higher risk for SGA; ZDV-3TC-NVP was associated with higher risk of stillbirth, very preterm birth, and neonatal death; and ZDV-3TC-LPV-R was associated with higher risk for preterm birth, very preterm birth, and neonatal death.

Conclusions And Relevance: Among infants exposed to ART from conception, TDF-FTC-EFV was associated with a lower risk for adverse birth outcomes than other ART regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.2222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726309PMC
October 2017
-->