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BackgroundAntiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate.MethodsThis multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of

BackgroundIntensified viral load monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies.MethodsWe used an individual Monte Carlo simulation to describe longitudinal ART adherence and viral load from conception until 2 years' postpartum. We applied national and international guidelines for viral load monitoring to the simulated data. We compared guidelines on the percentage of women receiving viral load monitoring and the percentage of women monitored at the time of elevated viral load.ResultsCoverage of viral load monitoring in pregnancy and breastfeeding varied markedly, with between 14% and 100% of women monitored antenatally and 38-98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved more than 95% testing in pregnancy but this was much lower (14-83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated viral load more than 1000 copies/ml were successfully detected by monitoring (range, 20-50%).DiscussionAlthough further research is needed to understand optimal viral load frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated viral load in pregnant and breastfeeding women.

Introduction: Most African countries perform infant HIV testing at 6 weeks or later. The addition of targeted testing at birth may improve retention in care, treatment outcomes and survival for HIV-infected infants. Methods: HIV-exposed infants were screened as part of the Early Infant Treatment (EIT) study in Botswana. Screened infants were [greater than or equal to]35 weeks gestational age and [greater than or equal to]2000 g at birth. Risk factors for mother-to-child transmission (MTCT) were assessed by maternal obstetric card or verbally. Risk factors included 400 copies/mL, poor maternal ART adherence, lack of maternal zidovudine (ZDV) in labour, or lack of infant post-exposure prophylaxis. Infants underwent dried blood spot testing by Roche Cobas Ampliprep/Cobas Taqman HIV-1 qualitative PCR. Results: From April2015 to April2016, 2303 HIV-exposed infants were tested for HIV in the EIT study. Of these, 369 (16%) were identified as high risk for HIV infection by information available at birth, and 12 (0.5% overall, 3.25% of high risk) were identified as HIV positive at birth. All 12 positive infants were identified as high risk at the time of screening, and only 2 risk factors were required to identify all positive infants: either Conclusions: In utero MTCT occurred only among infants identified as high risk at delivery, using information available from the mother or obstetric record. Birth testing that targets high-risk infants based on maternal ART receipt is likely to identify the majority of in utero HIV transmissions, and allows early ART initiation for these infants. Keywords: HIV; mother-to-child transmission; children; paediatrics; vertical transmission; viral suppression, 1 | INTRODUCTION The World Health Organization (WHO) recommends HIV testing for all HIV-exposed infants at 4 to 6 weeks of age [1], based on studies demonstrating the benefits of [...]

: 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 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy 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 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., INTRODUCTION Multiple studies have reported that tenofovir alafenamide (TAF) and dolutegravir (DTG) are associated with clinically significant weight gain, with risk of treatment‐emergent obesity (body mass index, or BMI, >30) [...]

: Introduction: Despite declining risk of vertical HIV transmission, prophylactic cotrimoxazole (CTX) remains widely used to reduce morbidity and mortality in the event of HIV infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo‐controlled trial of infant CTX prophylaxis, we sought to quantify emergence of antibiotic resistance. Methods: HIV‐exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX or placebo between 14 and 34 days of life and continued through 15 months. Stool samples were collected from a subset of participating infants at randomization, three, and six months, and stored at −70°C prior to culture. Specimens that grew Escherichia coli (E. coli) or Klebsiella species (Klebsiella spp.) underwent antibiotic susceptibility testing by Kirby Bauer method using CTX (CTX 1.25/23.75 μg) and Amoxicillin (10 μg) in Mueller Hinton agar. Fisher's exact testing was used to compare prevalence of resistance by randomization arm (CTX/placebo). Results and Discussion: A total of 381 stool samples from 220 infants were cultured: 118 at randomization, 151 at three months, and 112 at six‐months. E. coli was isolated from 206 specimens and Klebsiella spp. from 138 specimens. Resistance to CTX was common in both E. coli and Klebsiella spp. at the randomization visit (52.2% and 37.7% respectively) and did not differ by study arm. E. Coli isolates from CTX recipients at three and six months had 94.9% and 84.2% CTX resistance, as compared with 51.4% and 57.5% CTX resistance in isolates from placebo recipients (p=0.01). Klebsiella spp. isolates from CTX recipients had 79.0% and 68.8% CTX resistance at three and six months, as compared with 19.1% and 14.3% in isolates from placebo recipients (p Conclusions: HIV‐exposed infants randomized to CTX prophylaxis had increased CTX‐resistant commensal gastrointestinal bacteria compared with placebo recipients. Additional research is needed to determine the longer‐term clinical, microbiologic, and public health consequences of antimicrobial resistance selected by infant CTX prophylaxis., Introduction The World Health Organization (WHO) recommends cotrimoxazole (CTX) prophylaxis for HIV‐exposed infants at risk of postnatal HIV transmission, continuing until six weeks after breastfeeding cessation (with confirmation of negative [...]

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the United States in June and July 1997. Two concurrent outbreaks were investigated through independent case-control studies in Michigan and [...]

Abstract Background Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes. Methods Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States. Results During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02). Conclusions We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero.

Background: Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV‐infected adults, possibly related to cytokine‐mediated inflammation. Methods: To evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six‐months postpartum for the prevention of mother‐to‐child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA. All women attained viral suppression ( Results: Four cytokines showed a difference in expression between the treatment arms, all in a proinflammatory direction for the ABC arm: CD40LG 1.82‐fold, (p=.027); IL‐8 3.16‐fold (p=.020); LTA 2.82‐fold, (p=.008); and CCL5 −1.67‐fold, (p=.035). At 12‐months postpartum, 6‐months after antiretroviral discontinuation, cytokine expression was similar by treatment arm. Conclusions: We conclude that ABC may upregulate proinflammatory cytokines at the transcriptional level in this population., Introduction Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction (MI) in HIV‐infected adults, possibly related to cytokine‐mediated inflammation; however, no consistent outcome has been found [...]