Index-linked Assisted HIV Self-Testing for Children 2-14 Years: Results of a Pilot Evaluation in Ethiopia.

BACKGROUND: Case identification remains a challenge to reaching the United Nations 95-95-95 targets for children with HIV. While the World Health Organization approved oral mucosal HIV self-testing (HIVST) for children over 2 years in 2019, there is little information on HIVST for pediatric case identification in Ethiopia. SETTING: Nine health facilities across Ethiopia. METHODS: We implemented a pilot program from November 2021-April 2022 to assess acceptability and feasibility of using HIVST to screen children 2-14 years of adult index clients, (i.e., parents/caregivers living with HIV and on antiretroviral therapy). HIV-positive adults who had children with unknown HIV status were given HIVST kits (OraQuick®) to screen their children at home. Parents/caregivers were asked to report results telephonically and bring children screening positive to the health facility for confirmatory HIV testing. We defined HIVST acceptability as ≥50% of parents/caregivers accepting testing and ≥50% reporting results within seven days of receiving a test kit. Feasibility was defined as ≥60% of children with a reactive HIVST receiving confirmatory testing and <5 serious social harms reported per 1000 kits distributed. RESULTS: Overall, 1496 of 1651 (91%) parents/caregivers accepted HIVST kits to test their children at home and 1204 (71%) reported results within seven days. Of 17 children (1%) with reactive results, 13 (76%) received confirmatory testing; of which 7 (54%) were confirmed to be HIV-positive. One serious social harm was reported. CONCLUSION: Providing adult parents/caregivers with HIVST kits to screen their children at home is an acceptable and feasible strategy to reach untested children and improve pediatric case finding in a low prevalence setting.

An observational cohort study to investigate the impact of dolutegravir in pregnancy and its obesogenic effects on the metabolic health of women living with HIV and their children: Study protocol.

INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. MATERIALS & METHODS: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. DISCUSSION: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.

Association between maternal HIV status and postpartum depressive symptoms in Botswana.

Few studies have evaluated postpartum depression (PPD) in women living with HIV (WLHIV) in Botswana, a high prevalence HIV setting. The Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate PPD symptoms in WLHIV (n = 300) and women who are HIV-uninfected (n = 131) in the Tshilo Dikotla study, an observational cohort study with a nested randomized trial. The EPDS was administered at 2, 6, and 12 months postpartum. We assessed the association of (1) HIV infection and (2) antiretroviral therapy (ART) with odds of PPD symptoms (EPDS ≥ 10 or thoughts of self-harm) in the first year postpartum using generalized estimating equations. Of WLHIV, 24 (8.00%) had PPD symptoms at one or more follow-up time points, compared to 9 (6.9%) women who were HIV-seronegative. There was no association between HIV status and PPD symptoms (adjusted odds ratio [aOR]:1.69, 95% confidence interval [CI]: 0.73-3.93, p = 0.225); however, WLHIV on efavirenz-based ART regimens had higher odds of experiencing PPD symptoms compared to dolutegravir-based ART (aOR:3.05, 95% CI:1.16-8.03, p = 0.024).

Feasibility and acceptability of point of care testing for sexually transmitted infections in outpatient clinics offering integrated services in Eswatini.

BACKGROUND: Lack of point of care testing (POCT) for sexually transmitted infections (STIs) is a continuing missed opportunity in Sub-Saharan Africa. We assessed feasibility and acceptability of STI POCT in Eswatini. METHODS: STI POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) was piloted among sexually active adults 18-45 years attending two urban outpatient clinics offering HIV services. Females were randomized 1:1 to provide urine or vaginal swab and all males provided urine samples for CT/NG testing using Cepheid CT/NG cartridges on existing GeneXpert platforms. Results were returned in-person or by telephone call. We assessed duration of procedures and participant and healthcare worker acceptability of services (5-point Likert scale), time spent on STI POCT services, and correlates of CT/NG infection. RESULTS: Of 250 adults triaged, 99% (248/250) accepted STI POCT, including 44% (109/248) people living with HIV. STI POCT procedures took a median of 3:22 hours. Most adults (90%, 224/248), received results within a day (61% same day, 29% next day). CT/NG was detected among 22% (55/248): 31/55 CT, 21/55 NG and 3/55 coinfections. Youth 18-25 years, history of any sexual intercourse, and condom-less sex within the previous 7 days were significantly associated with CT/NG detected (p < 0.05). Most adults with CT/NG were treated (51/55, 93%). Most participants were satisfied with STI POCT (217/241, 90%), and would accept again/recommend it. All 32 healthcare workers who participated were satisfied with STI POCT. CONCLUSION: STI POCT was feasible, acceptable, and identified a high prevalence of STIs, highlighting the urgent need for this testing.

Guidelines for tuberculosis screening and preventive treatment among pregnant and breastfeeding women living with HIV in PEPFAR-supported countries.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV, including pregnant and breastfeeding women. Given the President's Emergency Plan for AIDS Relief (PEPFAR)'s investment in TPT services for persons living with HIV as a strategy to prevent TB as well as uncertainty in guidelines and policy regarding use of TPT during pregnancy and the postpartum period, we conducted a review of current relevant national guidelines among PEPFAR-supported countries. METHODS: Our review included 44/49 PEPFAR-supported countries to determine if TB screening and TPT are recommended specifically for pregnant and breastfeeding women living with HIV (WLHIV). National guidelines reviewed and abstracted included TB, HIV, prevention of vertical HIV transmission, TPT, and any other relevant guidelines. We abstracted information regarding TB screening, including screening tools and frequency; and TPT, including timing, regimen, frequency, and laboratory monitoring. RESULTS: Of 44 PEPFAR-supported countries for which guidelines were reviewed, 66% were high TB incidence countries; 41% were classified by WHO as high TB burden countries, and 43% as high HIV-associated TB burden countries. We found that 64% (n = 28) of countries included TB screening recommendations for pregnant WLHIV in their national guidelines, and most (n = 35, 80%) countries recommend TPT for pregnant WLHIV. Fewer countries included recommendations for breastfeeding as compared to pregnant WLHIV, with only 32% (n = 14) mentioning TB screening and 45% (n = 20) specifically recommending TPT for this population; most of these recommend isoniazid-based TPT regimens for pregnant and breastfeeding WLHIV. However, several countries also recommend isoniazid combined with rifampicin (3RH) or rifapentine (3HP). CONCLUSIONS: Despite progress in the number of PEPFAR-supported countries that specifically include TB screening and TPT recommendations for pregnant and breastfeeding WLHIV in their national guidelines, many PEPFAR-supported countries still do not include specific screening and TPT recommendations for pregnant and breastfeeding WLHIV.

"We did more than survive": lessons learned from studies of risk and resilience of young people growing up with HIV and mental health needs.

Despite advances in HIV-treatment, adolescents and young adults (AYA) with HIV (AYAHIV) face myriad challenges. They are less likely than children and older adults to be virally suppressed and are at higher risk for mental health conditions compared to their peers who do not have HIV. AYA are also developing in the context of numerous biomedical, neurocognitive, and psychosocial developmental changes. Normative challenges during this time can be exacerbated by HIV and can result in significant physical and mental health problems. Yet, many AYAHIV have shown resilience with positive assets and resources and few health or mental health problems. Historically research has had a risk-focused approach to understanding AYAHIV needs. This paper discusses the rationale for a shift from a risk-focused only approach to one that examines AYAHIV needs from both a risk and resilience perspective. This paper presents: (1) epidemiological data on AYAHIV; (2) conceptual models for understanding both risk (e.g., poverty, stress, trauma, limited resources) and resilience/protective factors (e.g., family and peer support, future orientation, problem-solving skills); (3) global data examining risk and protective factors for physical and mental health challenges; and (4) promising interventions that incorporate elements of resilience to improve overall outcomes among AYAHIV.

Growth Trajectories Over the First Year of Life Among Early-Treated Infants with Human Immunodeficiency Virus and Infants Who are Human Immunodeficiency Virus-Exposed Uninfected.

OBJECTIVE: To investigate the role of early antiretroviral therapy (ART) on growth trajectories of infants with human immunodeficiency virus (IHIV) in the first year of life. STUDY DESIGN: As part of a clinical trial of early ART in Johannesburg, South Africa (2015-2018), 116 IHIV diagnosed within 48 hours of birth were started on ART as soon as possible, and 80 uninfected infants born to mothers living with HIV (IHEU) were enrolled. Both groups were followed prospectively from birth through 48 weeks and growth parameters collected. The groups were compared and risk factors for poor growth investigated, in the full cohort and among IHIV separately. RESULTS: IHIV had lower mean weight-for-age Z-scores (WAZ) than IHEU at 4 and 8 weeks (-1.17 [SE:0.14] vs -0.72 [0.14], P = .035 and -1.23 [0.15] vs -0.67 [0.14], P = .012). Although there was some closing of the gap over time, means remained lower in IHIV through 48 weeks. In length-for-age Z-scores (LAZ), differences widened over time and IHIV had lower Z-scores by 48 weeks (-1.41 [0.15] vs -0.80 [0.18], P = .011). Deficits in WAZ and LAZ in IHIV vs IHEU were most marked among girls. IHIV with pre-ART viral load ≥1000 copies/ml had significantly lower weight-for-length and mid-upper arm circumference Z-scores across all time points through 48 weeks. CONCLUSIONS: IHIV on early ART had deficits in WAZ over the first 8 weeks of life and lower LAZ at 48 weeks than IHEU. Among IHIV, higher pre-ART viral load was associated with worse anthropometric indicators through 48 weeks.

Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

BACKGROUND: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. METHODS: The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. RESULTS: A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. CONCLUSIONS: In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

Prevalence and Correlates of Intimate Partner Violence Victimization Among Urban Adolescents and Young Adults Living With Perinatally-Acquired HIV Infection or Perinatal HIV Exposure.

INTRODUCTION: Because of privacy and ethical concerns, the data cannot be made available because of the sensitivity of the HIV data and the relatively small sample and ease of identifying people if a few demographics are known.Few studies have examined intimate partner violence (IPV) victimization among adolescents and young adults (AYAs) with perinatally acquired HIV-infection (PHIV) or perinatal HIV exposure without infection (PHEU) in the United States. The purpose of this study was to (1) estimate lifetime and past-year prevalence of IPV victimization and (2) examine correlates of IPV victimization by subtype (physical, psychological, and sexual) and severity (low, moderate, and severe). METHODS: Data came from the sixth interview of an ongoing New York City-based longitudinal study of primarily Black and Latinx AYAPHIV and AYAPHEU. We examined 232 participants (142 PHIV; 90 PHEU) who had reported having been in at least 1 romantic relationship. We used logistic regression models to explore the association between IPV victimization outcomes and select sociodemographic, psychiatric, and environmental factors. Models were adjusted for age, gender, race, ethnicity, and HIV status. RESULTS: IPV victimization prevalence was 84% for lifetime and 65% for the past year. There were no differences in IPV victimization prevalence by PHIV status. Having a recent substance use disorder, reporting higher levels of neighborhood stress, and being male were all positively associated with at least 1 IPV outcome; stronger familial relationships exhibited a protective effect. CONCLUSIONS: The present study suggests that the prevalence of IPV victimization among AYAPHIV and AYAPHEU is exceedingly high that warrants targeted IPV screening and programming for this population.

Maternal and birth outcomes in pregnant people with and without HIV in the Western Cape, South Africa.

INTRODUCTION: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation. METHODS: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression. RESULTS: Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32 015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19 157) were on ART preconception, 29% (N = 9276) initiated ART during pregnancy and 11% (N = 3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04-1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11-1.22 for LBW and 1.14-1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55-6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89-9.01). CONCLUSIONS: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV.