Antiretroviral Therapy In Pregnancy Research Articles

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A). There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature.

Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA. Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple safety and tolerability concerns with older regimens, there are now multiple options of regimens that are highly efficacious and have good safety data in pregnancy. Most pregnant patients who are virally suppressed on a well-tolerated regimen are able to safely continue those medications during pregnancy.

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

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

Use of integrase inhibitors vs protease inhibitors is associated with improved HIV viral suppression

Current guidelines for antiretroviral therapy in pregnancy include the use of a dual-nucleoside reverse transcriptase inhibitor with either an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, although there is no designation of which is the preferred option. This study aimed to compare viral suppression at delivery among patients on dual-nucleoside reverse transcriptase inhibitors combined with either an integrase strand transfer inhibitor or a protease inhibitor. A hypothesis was made that the incidence of viral suppression is higher with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with an integrase strand transfer inhibitor than with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with a protease inhibitor. This study was an observational study of pregnant patients living with HIV who received prenatal care and delivered after 20 weeks of gestation at an urban safety net hospital. All pregnant patients with HIV were referred to a centralized clinic for HIV counseling, medication management, and prenatal care. Antiretroviral therapy was continued or initiated according to protocols based on national guidance. Among patients on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor vs protease inhibitor at delivery, we compared the demographics and HIV disease characteristics, including year of diagnosis, viral load, and antiretroviral therapy class. The outcome of interest was viral suppression at delivery, defined as a viral load of <50 copies/mL. From January 2011 to December 2021, 604 patients on dual-nucleoside reverse transcriptase inhibitor met the inclusion criteria, including 411 patients (68%) on protease inhibitor and 193 patients (32%) on integrase strand transfer inhibitor at delivery. Demographic distribution was similar, and prenatal care was initiated at 12 weeks of gestation. Among the integrase strand transfer inhibitor group, 101 (17%) were on antiretroviral therapy at initiation of prenatal care compared with 169 (28%) in the protease inhibitor group. At delivery, the frequency of viral load suppression was higher among those on an integrase strand transfer inhibitor (147/193 [76%]) than among those on a protease inhibitor (275/411 [67%]) (odds ratio, 1.59; 95% confidence interval, 1.08-2.33). Among those with a detectable virus, quantitative viral load was not different. During the study period, the use of a protease inhibitor decreased, whereas the use of an integrase strand transfer inhibitor increased. Among pregnant patients living with HIV, viral suppression was more common among those on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor than among those on a dual-nucleoside reverse transcriptase inhibitor backbone protease inhibitor at delivery. Our results support the use of dual-nucleoside reverse transcriptase inhibitor with integrase strand transfer inhibitor as a first-line antiretroviral therapy regimen in pregnancy.

Dolutegravir in Pregnancy as Compared With Current HIV Regimens in the United States

ABSTRACT For those pregnant and positive for the HIV infection, the first-line antiretroviral therapy (ART) is a dolutegravir-based regimen. This regimen is more effective among nonpregnant adults when compared with other types of ART (it has a high barrier of resistance and fewer drug interactions than other types and is less likely to be discontinued due to adverse effects). Whereas the effectiveness, efficacy, and safety of dolutegravir in pregnancy have been compared with efavirenz in randomized trials, data comparing dolutegravir to protease inhibitor–based, integrase strand-transform inhibitor (INSTI)–based, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART regimens commonly used in pregnancy within the United States are limited. Since April 2007, some 22 sites in the United States and Puerto Rico enrolled HIV-infected pregnant persons and their infants within 72 hours following birth into the SMARTT Dynamic cohort. The current analysis entailed using the Pediatric HIV/AIDS Cohort Study SMARTT (Surveillance and Monitoring for ART Toxicities) protocol for evaluation of participants enrolled in the SMARTT Dynamic cohort through January 1, 2020, whose initial ART in pregnancy included oral rilpivirine, atazanavir-ritonavir, darunavir-ritonavir, raltegravir, and elvitegravir-cobicistat, in combination with dolutegravir, abacavir-lamivudine, tenofovir disoproxil fumarate–emtricitabine, tenofovir disoproxil fumarate–lamivudine, or tenofovir alafenamide fumarate–emtricitabine. Definition of the initial ART was the first ART regimen recorded in pregnancy, whether initiated before conception or during pregnancy. Outcomes included viral suppression at delivery, low birth weight and very low birth weight (&lt;2500 and &lt;1500 g), preterm and very preterm birth (at &lt;37 and &lt;32 weeks' gestation, respectively), small for gestational age (SGA), and neonatal death within 14 days after birth. Composite outcomes evaluated included any adverse birth outcome and any severe adverse birth outcome. The authors evaluated viral suppression at delivery, along with adverse birth outcomes in persons with an initial treatment regimen of dolutegravir for HIV infection when compared with those whose initial regimen included other contemporary ART drugs commonly prescribed in the Europe and the United States. In those participants who received dolutegravir, viral suppression was present at delivery in 96.7%; corresponding rates were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs dolutegravir were −13.0 percentage points [95% confidence interval {CI}, −17.0 to −6.1], −17.0 percentage points [95% CI, −27.0 to −2.4], and −7.0 percentage points [95% CI, −13.3 to −0.0], respectively). The observed risks of preterm birth were 13.6% to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being SGA did not differ substantially between dolutegravir and other, non–dolutegravir-based ART. Although these contribute important information to the literature, the study has some limitations. There was limited information on some preterm birth variables, such as important predictors of low birth weight and preterm birth (ie, previous preterm birth, parity, and prepregnancy body mass index). Furthermore, the analysis involved participants from a large multisite cohort study, but samples of participants receiving INSTIs were small, thereby limiting both the ability to detect small differences in adverse birth outcomes and the ability to conduct stratified analyses in accordance to ART initiation timing. The authors of the study note that their results provide evidence suggesting lower levels of effectiveness in suppression at delivery using atazanavir-ritonavir and raltegravir than dolutegravir. Therefore, they suggest that darunavir-ritonavir is a reasonable alternative when dolutegravir use is not feasible.

Key data from AIDS 2022.

We report on the highlights ofthe 24th International AIDS Conference, held in Montreal in 2022. We address three main themes: human immunodeficiency virus (HIV) targets and cascades, HIV and sexually transmitted infection prophylaxis, and HIV treatment, including the use of antiretroviral therapy in pregnancy.

Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States

BackgroundData on the effectiveness and safety of dolutegravir-based antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy as compared with other ART regimens commonly used in the United States and Europe, particularly when initiated before conception, are limited.MethodsWe conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included dolutegravir, atazanavir–ritonavir, darunavir–ritonavir, oral rilpivirine, raltegravir, or elvitegravir–cobicistat. Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non–dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results.ResultsOf the pregnancies in the study, 120 were in participants who received dolutegravir, 464 in those who received atazanavir–ritonavir, 185 in those who received darunavir–ritonavir, 243 in those who received rilpivirine, 86 in those who received raltegravir, and 159 in those who received elvitegravir–cobicistat. The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception. Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were 84.0% for atazanavir–ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir–cobicistat (adjusted risk differences vs. dolutegravir, −13.0 percentage points [95% confidence interval {CI}, −17.0 to −6.1], −17.0 percentage points [95% CI, −27.0 to −2.4], and −7.0 percentage points [95% CI, −13.3 to −0.0], respectively). The observed risks of preterm birth were 13.6 to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between non–dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar.ConclusionsAtazanavir–ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non–dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.)

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.

Protease inhibitor-based antiretroviral therapy in pregnancy: effects on hormones, placenta, and decidua.

The use of antiretroviral therapy (ART) in pregnancy is important for maternal health, and has been successful in reducing vertical transmission rates to almost zero in those taking effective ART regimens with good adherence. However, there are reports of higher rates of low birthweight and preterm births in women with HIV, which can be further exacerbated by ART usage in pregnancy. Protease inhibitors, and ritonavir-boosted lopinavir in particular, might directly contribute to placental and uteroplacental pathology in part by altering plasma concentrations of the essential steroid hormones of pregnancy, progesterone and oestradiol. In this Review, we collate the increasing evidence of dysregulated maternal endocrinology, reproductive physiology, and placental compromise associated with protease inhibitors. Based on findings of placental and decidual effects, we recommend that ritonavir-boosted lopinavir should be avoided in pregnancy, in line with US and European guidelines. Long-term follow-up of children exposed to protease inhibitors in utero is also recommended.

Brief Report: Viral Load Monitoring in Pregnancy to Predict Peripartum Viremia in South Africa.

Enhanced postnatal prophylaxis is recommended in infants of women with viremia during labor, as identified by viral load (VL) testing late in pregnancy. However, data on the use of antenatal VL to predict peripartum viremia are few, particularly in women starting antiretroviral therapy (ART) in pregnancy who experience initial VL declines. Between January 2016 and August 2017, we identified HIV-infected women who initiated ART (tenofovir, emtricitabine, and efavirenz) antenatally and had a VL <400 copies/mL before delivery in Cape Town, South Africa. VLs were repeated postdelivery, and sensitivity, specificity, and positive and negative likelihood ratios (LR+ and LR-) for antenatal VL <100 copies/mL in predicting peripartum VLs <100 and <400 copies/mL were calculated. Among 322 women (median age 29 years, 44% with a history of ART use, median gestation of antenatal VL 33 weeks), antenatal VL was <100 copies/mL in 89% and 100-400 copies/mL in 11%. At a median 9 days postpartum, 91%, 7%, and 2% of women had a VL <100, 100-400, and >400 copies/mL, respectively. Sensitivity of antenatal VL <100 copies/mL in predicting peripartum VL <100 copies/mL was 0.95 (95% confidence interval: 0.92 to 0.97), and specificity was 0.71 (95% confidence interval: 0.51 to 0.87; LR+ 3.28, LR- 0.07). Performance was slightly weaker to detect peripartum VL <400 copies/mL but was similar across strata of gestation at antenatal VL and history of ART use. Antenatal VL is a useful predictor of peripartum viremia in women who started ART in pregnancy and attained a VL <400 copies/mL antenatally and may be used to target enhanced postnatal prophylaxis interventions.

The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort

PurposeThe purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark...

Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa.

BackgroundMechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy.MethodsWomen with HIV enrolled at median 15 weeks’ gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery <37 weeks), 30 SGA (weight for age ≤10th percentile) cases, and 30 controls (term, weight for gestational age >25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry.ResultsPTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16–) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1β levels in monocytes were significantly lower in PTD women initiating ART in pregnancy.ConclusionLow immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy.

Pregnancy and Birth Outcomes Among Women on Antiretroviral Therapy: A Long-term Retrospective Analysis of Data from a Major Tertiary Hospital in North Central Nigeria.

Background and Objective:Antiretroviral therapy (ART) has transformed human immune deficiency virus (HIV) infection from a death sentence to a chronic syndrome, allowing infected individuals to lead near-normal lives, including achieving pregnancy and bearing children. Notwithstanding, concerns remain about the effects of ART in pregnancy. Previous studies suggested contradictory associations between ART and pregnancy. This study determined birth outcomes in pregnant women who accessed ART between 2004 and 2017 at a major tertiary hospital in North Central Nigeria.Methods:This was a retrospective study of 5,080 participants. Ethical clearance was obtained from the Institutional Review Board of the Harvard T. H. Chan School of Public Health Boston. A pro forma for data abstraction was designed and used to collect data. ed data were sorted and managed using SPSS® version 22. The Chi-square test was used to calculate the proportions of pregnancy outcomes. One-way analysis of variance was used to test the effect of antiretroviral drug regimens on mean birth weight and gestational age at delivery. All levels of significance were set at p 0.05.Results:Pregnancy outcomes were recorded as live birth (99.8%), stillbirth (0.2%), preterm delivery (6.6%), and low birth weight (23%). There was a statistically significant association between ART in pregnancy and low birth weight {χ2 [(5, n = 3439) = 11.99, p = 0.04]}. The highest mean birth weights were recorded in participants who received drug combinations with protease inhibitors or efavirenz, in contrast to participants who received Nevirapine, stavudine and Emtricitabine/Tenofovirbased regimens. However, there was no significant difference in the gestational age of babies at birth for the six ART regimens in the study.Conclusion and Global Health Implications:Findings support the benefits of ART in pregnancy, which is in line with the testing and treatment policies of the 90-90-90 targets for ending HIV by the year 2030.

In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice

Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.

Community-based adherence clubs for postpartum women on antiretroviral therapy (ART) in Cape Town, South Africa: a pilot study

BackgroundWith an increasing number of countries implementing Option B+ guidelines of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, there is urgent need to identify effective approaches for retaining this growing and highly vulnerable population in ART care.MethodsNewly postpartum, breastfeeding women who initiated ART in pregnancy and met eligibility criteria were enrolled, and offered the choice of two options for postpartum ART care: (i) referral to existing network of community-based adherence clubs or (ii) referral to local primary health care clinic (PHC). Women were followed at study measurement visits conducted separately from either service. Primary outcome was a composite endpoint of retention in ART services and viral suppression [VS < 50 copies/mL based on viral load (VL) testing at measurement visits] at 12 months postpartum. Outcomes were compared across postpartum services using chi-square, Fisher’s exact tests and Poisson regression models. The primary outcome was compared across services where women were receiving care at 12 months postpartum in exploratory analyses.ResultsBetween February and September 2015, 129 women (median age: 28.9 years; median time postpartum: 10 days) were enrolled with 65% opting to receive postpartum HIV care through an adherence club. Among 110 women retained at study measurement visits, 91 (83%) achieved the composite endpoint, with no difference between those who originally chose clubs versus those who chose PHC services. Movement from an adherence club to PHC services was common: 31% of women who originally chose clubs and were engaged in care at 12 months postpartum were attending a PHC service. Further, levels of VS differed significantly by where women were accessing ART care at 12 months postpartum, regardless of initial choice: 98% of women receiving care in an adherence club and 76% receiving care at PHC had VS < 50 copies/mL at 12 months postpartum (p = 0.001).ConclusionThis study found comparable outcomes related to retention and VS at 12 months postpartum between women choosing adherence clubs and those choosing PHC. However, movement between postpartum services among those who originally chose adherence clubs was common, with poorer VS outcomes among women leaving clubs and returning to PHC services.Trial registrationClinicalTrials.gov NCT02417675, April 16, 2015 (retrospectively registered).

Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy.

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] -5.9% [95% CI, -6.4 to -5.4] versus REF [n = 64] -4.3% [95% CI, -4.8 to -3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: -2.0% [95% CI, -2.5 to -1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] -1.8% [95% CI, -2.2 to -1.4] versus REF [n = 69] -2.9% [95% CI, -3.3 to -2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] -3.1% [95% CI, -3.6 to -2.6]; REF [n = 29] +0.1% [95% CI, -0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Perspectives of pregnant women, family members and health professionals on medication adherence in Nigeria

ABSTRACT Nigeria has the highest burden of mother-to-child transmission of human immunodeficiency virus (HIV) worldwide. Pregnant women living with HIV in Nigeria face challenges adhering to antiretroviral therapy (ART). We explored the perspectives of pregnant women living with HIV, family members, friends and health professionals to understand adherence to ART. Pregnant women, family members, friends and health professionals recruited from four HIV treatment sites in Nigeria participated in semi-structured interviews and focus groups. Thematic analysis was conducted and themes and sub-themes were mapped against the Theory of Planned Behaviour comprising behavioural, normative and control beliefs. Overall, 74 participants took part in the study. Common behavioural beliefs comprised maintaining the mother's and unborn child's health and success of having HIV-negative children from previous pregnancies. Common normative beliefs involved partner and family support for medication taking and medication refill visits. Common control beliefs comprised fear of discrimination and stigmatisation. Results showed that adherence to ART in pregnancy is intricate. Hence, before interventions are developed to change adherence behaviours in pregnant women tailored strategies should be devised that address the salient beliefs that influence adherence during pregnancy.

Infectious morbidity of breastfed, HIV-exposed uninfected infants under conditions of universal antiretroviral therapy in South Africa: a prospective cohort study

Without breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected (HEU) infants have greater infectious morbidity than HIV-unexposed (HU) infants. We hypothesised that with the introduction of universal maternal ART, breastfed HEU and HU infants would have similar morbidity. We prospectively studied a cohort of HIV-infected pregnant women initiating ART, and a parallel group of HIV-uninfected pregnant women, starting from their first antenatal care visit at the Gugulethu Midwife Obstetrics Unit in Cape Town, South Africa. All pregnant women attending their first antenatal care visit were eligible for enrolment if aged 18 years or older and planning to deliver in Cape Town, without gestational age restrictions. HIV-infected women were participants of the Maternal Child Health ART (MCH-ART) study, and HIV-uninfected women were participants of the HIV-Unexposed Uninfected (HU2) study. All enrolled women were followed up during pregnancy and through delivery. At the early neonatal visit (scheduled for the first week after birth), mother-infant pairs who practiced any breastfeeding in the first 7 days of life were eligible for further postnatal follow-up for at least 12 months post partum. HIV infection was excluded among HEU infants at ages 6 weeks and 12 months by PCR. We evaluated the effect of HIV exposure on two primary outcomes: hospitalisation (all-cause and infection-related admission to hospital) and longitudinal prevalence of child infectious illness (diarrhoea and presumed lower respiratory tract infection [LRTI]). Hospitalisation data were abstracted from routine health records. Crude and adjusted incidence rate ratios (aIRRs; with adjustment for maternal HIV disease severity, timing of ART initiation, breastfeeding, timely vaccination, and birth outcomes [gestational size and age]) for infection-related hospitalisations were calculated from Poisson regression models (with variance corrected for clustering). Prevalence of infant infectious illness was based on maternal self-report for the preceding 2 weeks of each visit, with questions based on Demographic and Health Survey (DHS) questionnaires. Infants who acquired HIV infection during follow-up were excluded from this analysis. MCH-ART is registered on ClinicalTrials.gov, NCT01933477. Pregnant women were recruited between March 20, 2013, and Aug 19, 2015. Mother-infant pairs (HEU, n=459; HU, n=410) were followed up for a median of 12 months until March 24, 2017. Compared with HU infants, HEU infants had more infection-related hospitalisations between the age of 8 days and 3 months (HEU, 34·2 admissions per 100 child-years [24·4-47·9] vs 9·8 per 100 child-years [95% CI 5·1-18·8]; IRR 3·50 [95% CI 1·68-7·30]), but rates were similar at other ages. In infants aged 8 days to 3 months, infection-related hospitalisations for HEU infants with healthier mothers (n=84; ART initiation at <24 weeks' gestation, CD4 count >350 cells per μL, HIV viral load <4·0 log10 copies per mL: 15·88 admissions per 100 child-years [5·12-49·23]) approximated those of HU infants (9·77 per 100 child-years [5·08-18·78]; aIRR 1·28 [0·27-6·05]). HEU infants of mothers with late ART initiation (at ≥24 weeks' gestation) and advanced disease (CD4 count ≤350 cells per μL and HIV viral load ≥4·0 log10 copies per mL; n=44) had the highest admission rate (40·44 per 100 child-years [15·18-107·74]; aIRR 5·01 [1·50-16·71]). In this age group, reduced admissions were seen in HEU infants with optimal breastfeeding (initiated within 1 h of birth and exclusive through age 3 months) and timely vaccination (required doses received within 2 weeks of indicated age; n=90; 9·63 admissions per 100 child-years [2·41-38·49]). Between birth and age 6 months, HEU infants had an almost five times greater prevalence of LRTIs than HU infants (aPR 4·69 [2·40-9·17]), and a three-times greater prevalence of diarrhoeal illness (aPR 2·93 [1·70-5·07]). After age 6 months, these associations were ameliorated. Despite ART in pregnancy, breastfed HEU infants versus breastfed HU infants had transiently increased infectious morbidity risks in early infancy. However, differences were driven by factors potentially amenable to intervention, including delayed diagnosis and ART initiation in HIV-positive mothers, and suboptimal breastfeeding and vaccination of their infants. US National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, Fogarty Foundation and the Office of AIDS Research.

Cost-effectiveness of integrating postpartum antiretroviral therapy and infant care into maternal & child health services in South Africa.

BackgroundPoor engagement in postpartum maternal HIV care is a challenge worldwide and contributes to adverse maternal outcomes and vertical transmission. Our objective was to project the clinical and economic impact of integrated postpartum maternal antiretroviral therapy (ART) and pediatric care in South Africa.MethodsUsing the CEPAC computer simulation models, parameterized with data from the Maternal and Child Health–Antiretroviral Therapy (MCH-ART) randomized controlled trial, we evaluated the cost-effectiveness of integrated postpartum care for women initiating ART in pregnancy and their children. We compared two strategies: 1) standard of care (SOC) referral to local clinics after delivery for separate standard ART services for women and pediatric care for infants, and 2) the MCH-ART intervention (MCH-ART) of co-located maternal/pediatric care integrated in Maternal and Child Health (MCH) services throughout breastfeeding. Trial-derived inputs included: 12-month maternal retention in care and virologic suppression (SOC: 49%, MCH-ART: 67%), breastfeeding duration (SOC: 6 months, MCH-ART: 8 months), and postpartum healthcare costs for mother-infant pairs (SOC: $50, MCH-ART: $69). Outcomes included pediatric HIV infections, maternal and infant life expectancy (LE), lifetime HIV-related per-person costs, and incremental cost-effectiveness ratios (ICERs; ICER <US$903/YLS considered “cost-effective”).ResultsCompared to SOC, MCH-ART increased maternal LE (SOC: 25.26 years, MCH-ART: 26.20 years) and lifetime costs (SOC: $9,912, MCH-ART: $10,207; discounted). Projected pediatric outcomes for all HIV-exposed children were similar between arms, although undiscounted LE for HIV-infected children was shorter in SOC (SOC: 23.13 years, MCH-ART: 23.40 years). Combining discounted maternal and pediatric outcomes, the ICER was $599/YLS.ConclusionCo-located maternal HIV and pediatric care, integrated in MCH services throughout breastfeeding, is a cost-effective strategy to improve maternal and pediatric outcomes and should be implemented in South Africa.

641: Preconceptional antiretroviral therapy reduces local and systemic inflammation in pregnant women with human immunodeficiency virus

HIV-infected pregnant women have high rates of preterm birth (PTB). Multiple recent reports have suggested, counterintuitively, that women who start antiretroviral therapy (ART) prior to conception have higher rates of PTB than women who initiate ART in pregnancy. We hypothesized that this association, if real, is not mediated through inflammation and immune activation in the vagina and peripheral blood. We analyzed specimens from an ongoing prospective cohort study in Lusaka, Zambia. At the time of analysis, paired (vaginal, plasma) mid-trimester (16-20 weeks) samples from 494 women were available. To maximize information with available budget for this sub-study, we analyzed all specimens from HIV seropositive women and a random sample of HIV negative women, accounting for this with probability weighting in analyses. We further divided HIV-infected women into those on preconceptional ART versus those who started ART during pregnancy (after samples obtained). We measured a panel of 13 maternal plasma and 14 maternal vaginal fluid analytes using a multiplex immunoassay (MilliporeSigma, Darmstadt, Germany). We log-transformed concentrations and compared them across exposure categories with ANOVA. We analyzed 244 plasma specimens (153 HIV-uninfected, 51 HIV-infected on preconceptional ART, and 40 HIV- infected without preconceptional ART exposure) and 255 vaginal swabs (160 HIV-uninfected, 54 HIV-infected on preconceptional ART, and 41 HIV-infected without preconceptional ART exposure). When compared to HIV- uninfected women and HIV-infected women on preconceptional ART, women not on preconceptional ART had significantly higher concentrations of inflammatory plasma (IP10, IL-8, IFN-ɣ, IL-12p40, and sCD14) and vaginal (IL-1β, IL-10, sCD14) biomarkers as well as significantly lower concentrations of anti-inflammatory TGF-β in plasma and vaginal SLPI, an enzyme with anti-HIV properties (p< 0.05; no adjustment for multiple comparisons; Table). HIV-infected pregnant women without preconceptional ART exposure exhibited increased systemic and local inflammation in the second trimester of pregnancy. If recent reports associating preconceptional ART with PTB are correct, our study suggests the mechanism is not early local or systemic inflammation. Additional analyses to understand the interaction between these inflammatory markers, other PTB risk factors, and the vaginal microbiota are ongoing.