The Mental Health Effects and Experiences of Breastfeeding Decision-Making Among Postpartum Women Living with HIV.

Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.

Patient Perspectives on Telehealth for HIV and Mental Health Care at a Pediatric and Adolescent HIV Clinic in Washington, DC.

Despite the scale-up of telehealth for children and youth living with HIV during the COVID-19 pandemic, their experience and interest in continued telehealth use in the future is unknown. We conducted a quality improvement project to identify areas for improvement of telehealth delivery to children and youth living with HIV and evaluate youth's experiences when using telehealth for mental health services. Children and youth living with HIV (up to 24 years) seen at a specialty HIV program during 2020-2021 were surveyed regarding technology access, telehealth knowledge, barriers to telehealth use and interest in future telehealth use for HIV care. Youth (12-<24 years) who used telehealth for mental health services were surveyed regarding their experiences. Data were analyzed using descriptive statistics. Of the 170 patients in care, we surveyed 103 children and youth living with HIV (median age 17.6 years, 88.3% Black, 52.4% female, 77.7% perinatally infected), of whom 69.9% had prior telehealth use for their clinical visit. Most patients had access to a device with internet (99%) and were interested in future telehealth use for HIV care (87.4%). Reasons for not wanting to use telehealth included privacy concerns, distrust, discomfort with telehealth, preferring in-person visits, technology access issues and needing translation services. Most youth (81%) surveyed regarding telehealth for mental health services were satisfied and very likely to recommend it to others. Despite some reported barriers to telehealth, there is a high desirability for continued telehealth use among children and youth receiving HIV care.

Breastfeeding Among People With Human Immunodeficiency Virus in North America: A Multisite Study.

BACKGROUND: In North American countries, national guidelines have strongly recommended formula over breastmilk for people with human immunodeficiency virus (HIV) because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is <1% among virally suppressed people. Information regarding breastfeeding experience in high-resource settings is lacking. METHODS: A retrospective multisite study was performed for individuals with HIV who breastfed during 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. RESULTS: Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range, 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available ≥6 weeks after weaning. CONCLUSIONS: This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients with HIV who chose to breastfeed at any 1 location, and the need for further multisite studies to identify best care practices.

Prevention of Perinatal HIV Transmission in an Area of High HIV Prevalence in the United States.

OBJECTIVE: To evaluate the uptake of perinatal HIV preventive interventions by the risk of perinatal HIV transmission in mother-infant pairs in a high-HIV prevalence area in the US. STUDY DESIGN: This was a retrospective cohort study of mother-infant pairs with perinatal HIV exposure during 2013-2017 managed at a subspecialty pediatric HIV program in Washington, DC. We collected demographic data, maternal HIV history, delivery mode, maternal and infant antiretroviral drug (ARV) use, and infant HIV test results. We compared the uptake of recommended preventive interventions in low-risk (ie, mothers on antiretroviral therapy [ART] with viral suppression) and high-risk (mothers without ART or viral suppression) mother-infant pairs using the Pearson chi-square, Fisher exact, and Wilcoxon rank-sum tests and logistic regression. RESULTS: We analyzed 551 HIV-exposed infants (HEIs) and 542 mothers living with HIV. The majority of mothers received ARVs (95.5%), had HIV RNA ≤1000 copies/mL before delivery (81.9%), and received intrapartum zidovudine (ZDV; 65.5%). The majority of all HEIs were low risk (82.6%) and received postpartum ARVs (98.9%). Among the low-risk infants, 53.2% were delivered via cesarean delivery (CD), and 62.9% and 96.5% were administered intrapartum and postpartum ZDV, respectively. Among high-risk infants, 84.4% were delivered via CD, 78.1% received intrapartum ZDV, and 62.5% received combination ART. Nine high-risk infants acquired HIV perinatally. CONCLUSION: In an area of high HIV prevalence in the US, a large proportion of low-risk HEIs received intrapartum ZDV and were delivered via CD. We also observed missed opportunities for the prevention of perinatal HIV transmission.

Pediatric Antiretroviral Therapy.

Human immunodeficiency virus (HIV) is one of the most serious pediatric infectious diseases, affecting around 3 million children and adolescents worldwide. Lifelong antiretroviral treatment (ART) provides multiple benefits including sustained virologic suppression, restoration and preservation of immune function, decreased morbidity and mortality, and improved quality of life. However, access to ART, particularly among neonates and young infants, continues to be challenging due to limited number of suitable formulations and limited access to pediatric ARV drug. Moreover, children and adolescents living with HIV may experience long-term HIV- and ART-associated comorbidities including cardiovascular, renal, neurological, and metabolic complications. We provide an overview of currently available formulations, dosing, and safety considerations for pediatric antiretroviral drugs by drug classes and according to the three age groups including neonates, children, and adolescents.

A Comparison of Pediatric and Adult Safety Studies for Antipsychotic and Antidepressant Drugs Submitted to the United States Food and Drug Administration.

OBJECTIVE: To examine the differences in the adverse drug reaction (ADR) profile of antipsychotic and antidepressant agents between pediatric and adult patients in studies submitted to the Food and Drug Administration (FDA) during the drug development process. STUDY DESIGN: Clinical trials in adult and pediatric patients were conducted by sponsors as part of the drug development programs for antipsychotic and antidepressant agents, and ADR information was collected as part of those trials and submitted to the FDA. Data collection was conducted by reviewing publicly available FDA-authored reviews and FDA-approved product labels for 10 drugs with an antipsychotic or an antidepressant indication from 2007 to 2017. RESULTS: There were 308 drug and ADR combinations for the 10 drugs and drug combinations with 113 (36.7%) having a significantly different incidence in pediatric patients compared with adults. Sixty-eight (60.2%) of these ADRs had a significantly higher incidence in pediatric patients than in adults. Sedation was higher in 6 of the 10 drugs and drug combinations with risk differences ranging from 9.6 to 36.6%. CONCLUSIONS: This analysis indicates that there were significant differences between the pediatric and adult safety profiles of antipsychotic and antidepressant drugs. Sedation was the major ADR associated with the use of atypical antipsychotic drugs in pediatric patients. Clinicians caring for children should consider the ADR profile when prescribing antipsychotics and antidepressants in pediatric patients.

Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV.

INTRODUCTION: This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children. METHODS: A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration-time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied. DISCUSSION AND CONCLUSION: Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.

Growing up with perinatal human immunodeficiency virus-A life not expected.

AIM AND OBJECTIVES: To describe the lived experience of young adults with perinatally acquired HIV (PaHIV). BACKGROUND: With the advancement of the highly active antiretroviral treatment, PaHIV infection has transformed into a chronic lifelong illness that is faced by young adults who grew up with HIV. The known challenges that are associated with HIV are poverty, stigma and social and emotional isolation. DESIGN: This was a qualitative single-interview study of a convenience sample of PaHIV-infected young adults receiving care at a large metropolitan pediatric hospital. METHODS: The participants had individual face-to-face interviews which were audio-taped and transcribed verbatim. Themes were developed to describe their living space, and Max Van Manen's lifeworld guide was used to describe their lived experience. FINDINGS: Seventeen participants (eight males/nine females) were enrolled. Four major themes emerged: (i) limited social capital, especially when orphaned participants reflected on a life void of parental guidance; (ii) incomplete education and unemployment, participants described an idle existence; (iii) a harsh life, described as participants facing difficulties meeting their life's milestones; (iv) unanticipated adult issues, where participants described their limited ability to care for themselves and their children. Van Manen lifeworld themes also described the space they occupied, their memories growing up with PaHIV, their health care and relationships. CONCLUSION: Our study provides a valuable insight into the social and emotional difficulties faced by youth with PaHIV. The findings underscore the importance of extensive support and coordination of services between adult and pediatric providers to optimize long-term outcomes among young adults with PaHIV. RELEVANCE TO CLINICAL PRACTICE: The young adults with PaHIV require close attention and support from the healthcare providers, who can offer them a safe space to discuss lived experiences and support their ability to achieve full lives.

Disparities in achieving and sustaining viral suppression among a large cohort of HIV-infected persons in care - Washington, DC.

One goal of the HIV care continuum is achieving viral suppression (VS), yet disparities in suppression exist among subpopulations of HIV-infected persons. We sought to identify disparities in both the ability to achieve and sustain VS among an urban cohort of HIV-infected persons in care. Data from HIV-infected persons enrolled at the 13 DC Cohort study clinical sites between January 2011 and June 2014 were analyzed. Univariate and multivariate logistic regression were conducted to identify factors associated with achieving VS (viral load < 200 copies/ml) at least once, and Kaplan-Meier (KM) curves and Cox proportional hazards models were used to identify factors associated with sustaining VS and time to virologic failure (VL ≥ 200 copies/ml after achievement of VS). Among the 4311 participants, 95.4% were either virally suppressed at study enrollment or able to achieve VS during the follow-up period. In multivariate analyses, achieving VS was significantly associated with age (aOR: 1.04; 95%CI: 1.03-1.06 per five-year increase) and having a higher CD4 (aOR: 1.05, 95% CI 1.04-1.06 per 100 cells/mm(3)). Patients infected through perinatal transmission were less likely to achieve VS compared to MSM patients (aOR: 0.63, 95% CI 0.51-0.79). Once achieved, most participants (74.4%) sustained VS during follow-up. Blacks and perinatally infected persons were less likely to have sustained VS in KM survival analysis (log rank chi-square p ≤ .001 for both) compared to other races and risk groups. Earlier time to failure was observed among females, Blacks, publically insured, perinatally infected, those with longer standing HIV infection, and those with diagnoses of mental health issues or depression. Among this HIV-infected cohort, most people achieved and maintained VS; however, disparities exist with regard to patient age, race, HIV transmission risk, and co-morbid conditions. Identifying populations with disparate outcomes allows for appropriate targeting of resources to improve outcomes along the care continuum.

Successful management of haemophagocytic lymphohistiocytosis in an adolescent with newly diagnosed HIV/AIDS and histoplasmosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome characterised by persistent fevers, cytopenia, hepatosplenomegaly and systemic inflammation. Secondary HLH can be triggered by various aetiologies including infections, malignancies and autoimmune conditions. We highlight the complexity of HLH diagnosis and management by describing a case of an adolescent Salvadoran immigrant with HLH, newly diagnosed HIV, Streptococcal bacteraemia and disseminated histoplasmosis. The patient presented with neurological and ocular findings along with persistent fevers and cytopenia. He was diagnosed with HLH and treated with anakinra in addition to receiving treatment for HIV, Streptococcal bacteraemia and histoplasmosis. The patient's HLH resolved without corticosteroids or chemotherapy, which are considered the mainstays for HLH treatment. This case underscores the need for the evaluation and management of multiple infections and individualised management in patients presenting with HLH to achieve favourable outcomes.

Mpox (Monkeypox) Virus and Its Co-Infection with HIV, Sexually Transmitted Infections, or Bacterial Superinfections: Double Whammy or a New Prime Culprit?

Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections.

Experiences of adolescents and youth with HIV testing and linkage to care through the Red Carpet Program (RCP) in Kenya.

Adolescents and youth living with HIV (AYLHIV) experience worse health outcomes compared to adults. We aimed to understand the experiences of AYLHIV in care in the youth-focused Red-Carpet program in Kenya to assess the quality of service provision and identify programmatic areas for optimization. We conducted focus group discussions among 39 AYLHIV (15-24 years) and structured analysis into four thematic areas. Within the HIV testing theme, participants cited fear of positive results, confidentiality and stigma concerns, and suggested engaging the community and youth in HIV testing opportunities. Within the HIV treatment adherence theme, participants cited forgetfulness, stigma, adverse side effects, lack of family support, and treatment illiteracy as barriers to adherence. Most participants reported positive experiences with healthcare providers and peer support. In terms of the HIV status disclosure theme, AYLHIV cited concerns about their future capacity to conceive children and start families and discussed challenges with understanding HIV health implications and sharing their status with friends and partners. Youth voices informing service implementation are essential in strengthening our capacity to optimize the support for AYLHIV within the community, at schools and healthcare facilities.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.

Mechanistic Modeling of the Drug-Drug Interaction Between Efavirenz and Dolutegravir: Is This Interaction Clinically Relevant When Switching From Efavirenz to Dolutegravir During Pregnancy?

Following the 2021 World Health Organization's updated recommendations on the management of HIV infection, millions of people living with HIV are currently switched from efavirenz-based antiretroviral therapy to dolutegravir-based antiretroviral therapy. Pregnant individuals transitioning from efavirenz to dolutegravir might be at increased risk of insufficient viral suppression in the immediate postswitch period because both efavirenz- and pregnancy-related increases in hormone levels induce enzymes involved in dolutegravir metabolism, namely, cytochrome P450 3A4 and uridine 5'-diphospho-glucuronosyltransferase 1A1. This study aimed at developing physiologically based pharmacokinetic models to simulate the switch from efavirenz to dolutegravir in the late second and third trimester. To this end, the drug-drug interaction between efavirenz and the uridine 5'-diphospho-glucuronosyltransferase 1A1 substrates dolutegravir and raltegravir was first simulated in nonpregnant subjects. After successful validation, the physiologically based pharmacokinetic models were translated to pregnancy and dolutegravir pharmacokinetics following efavirenz discontinuation were predicted. Modeling results indicated that, at the end of the second trimester, both efavirenz concentrations and dolutegravir trough concentrations fell below respective pharmacokinetic target thresholds (defined as reported thresholds producing 90%-95% of the maximum effect) during the time interval from 9.75 to 11 days after dolutegravir initiation. At the end of the third trimester, this time interval spanned from 10.3 days to >4 weeks after dolutegravir initiation. These findings suggest that dolutegravir exposure in the immediate post-efavirenz switch period during pregnancy may be suboptimal, leading to HIV viremia and, potentially, resistance. The clinical implications of these findings remain to be substantiated by future studies.

High dose of darunavir in treatment-experienced HIV-infected adolescent results in virologic suppression and improved CD4 cell count.

We describe an unintentional significant overdose of darunavir in a treatment-experienced adolescent with decreased darunavir susceptibility and prior treatment failure on darunavir therapy. Minimal toxicity and improved virologic suppression observed with an overdose have prompted consideration of the continued use of a higher than recommended dose. Pharmacokinetic and pharmacodynamic evaluations justified the individualized use of high-dose darunavir, which resulted in virologic suppression, improved CD4 cell count, and resolution of toxicity.

Adolescents and Young Adults: The Pediatrician's Role in HIV Testing and Pre- and Postexposure HIV Prophylaxis.

Most sexually active youth in the United States do not believe that they are at risk for contracting HIV and have never been tested. Creating safe environments that promote confidentiality and respect, obtaining an accurate sexual and reproductive health assessment, and providing nonstigmatizing risk counseling are key components of any youth encounters. Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing and prophylaxis to adolescent and young adult (youth) patients. In light of persistently high numbers of people living with HIV in the United States and documented missed opportunities for HIV testing, the Centers for Disease Control and Prevention and the US Preventive Services Task Force recommend universal and routine HIV screening among US populations, including youth. Recent advances in HIV diagnostics, treatment, and prevention help support this recommendation. This clinical report reviews epidemiological data and recommends that routine HIV screening be offered to all youth 15 years or older, at least once, in health care settings. After initial screening, youth at increased risk, including those who are sexually active, should be rescreened at least annually, and potentially as frequently as every 3 to 6 months if at high risk (male youth reporting male sexual contact, active injection drug users, transgender youth; youth having sexual partners who are HIV-infected, of both genders, or injection drug users; youth exchanging sex for drugs or money; or youth who have had a diagnosis of or have requested testing for other sexually transmitted infections). Youth at substantial risk for HIV acquisition should be routinely offered HIV preexposure prophylaxis, and HIV postexposure prophylaxis is also indicated after high-risk exposures. This clinical report also addresses consent, confidentiality, and coverage issues that pediatricians face in promoting routine HIV testing and HIV prophylaxis for their patients.

Metabolomics in Placental Tissue from Women Living with HIV.

It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

Short Communication:Outcomes of Dual Versus Triple Antiretroviral Drug Regimens Among Virally Suppressed Adults in the DC Cohort.

This study explored virological outcomes of two-drug (2DRs) and three-drug (3DRs) antiretroviral regimens in adults with HIV in the DC Cohort. We analyzed 310 treatment-experienced adults with sustained HIV RNA ≤50 copies/mL at baseline, 53 of whom switched to 2DRs and 257 continued 3DRs. Adults on 2DRs and 3DRs had similar demographics (median age 53.3 years, 76.8% cisgender male, 76.1% Black). Adults on 2DRs had more participants with ≥2 comorbidities (62.3% vs. 42.8%, p = .019), had a longer time since HIV diagnosis (median years 20.4 vs. 13.2, p = .017), and received the regimen of interest for a shorter duration (median years 1.3 vs. 3.3, p < .001) compared with adults on 3DRs. Adults receiving 2DRs had a higher, although nonsignificant, risk for virological failure (two consecutive HIV RNA ≥50 copies/mL) at 24 months follow-up than adults on 3DRs (6.7% vs. 1.7%, respectively; p = .10). Future analysis of the effectiveness of 2DRs is needed.

Clinical outcomes among adolescents living with HIV in Kenya following initiation on antiretroviral treatment.

In Kenya, HIV/AIDS remains a leading cause of morbidity and mortality among adolescents living with HIV (ALHIV). Our study evaluated associations between demographic and healthcare factors and HIV treatment outcomes among ALHIV in care in Kenya. This retrospective cohort study evaluated the clinical outcomes of newly diagnosed ALHIV enrolled in HIV care during January 2017-June 2018 at 32 healthcare facilities in Homabay and Kakamega Counties. Demographic and clinical data were abstracted from patient clinical records and registers during the follow up study period January 2017-through May 2019. ALHIV were stratified by age (10-14 versus 15-19 years). Categorical variables were summarized using descriptive statistics; continuous variables were analyzed using mean values. The latest available treatment and virological outcomes for ALHIV were assessed. 330 ALHIV were included in the study (mean age 15.9 years; 81.8% female, 63.0% receiving HIV care at lower-level healthcare facilities). Most (93.2%) were initiated on ART within 14 days of diagnosis; 91.4% initiated EFV-based regimens. Of those on ART, only 44.6% were active on care at the end of the study period. Of those eligible for viral load testing, 83.9% were tested with 84.4% viral suppression rate. Retention in care was higher at higher-level facilities (67.5%) compared to lower-level facilities (28.6%). Factors associated with higher retention in care were school attendance (aRR = 1.453), receipt of disclosure support (aRR = 13.315), and receiving care at a high-level health facility (aRR = 0.751). Factors associated with viral suppression included older age (15-19 years) (aRR = 1.249) and pre-ART clinical WHO stage I/II (RR = .668). Viral suppression was higher among older ALHIV. Studies are needed to evaluate effective interventions to improve outcomes among ALHIV in Kenya.

Advancing the prevention and treatment of HIV in children: priorities for research and development.

Safe and effective paediatric formulations of the most promising antiretroviral drugs are crucial to advance the treatment and prevention of HIV in neonates, infants, children, and adolescents. The WHO Paediatric Drug Optimization for HIV (PADO-HIV) group brings together stakeholders and experts every 2-3 years to identify priority products and define research gaps in the development of new HIV drugs and formulations for children in low-income and middle-income countries. PADO-HIV 5 met from Sept 27 to Oct 15, 2021. The group evaluated HIV agents from known and novel drug classes, oral and parenteral long-acting formulations, and developments in broadly neutralising antibodies, and included focused sessions on neonates and new delivery technologies. A list of medium-term and long-term priorities was generated, and research questions were defined. This forward-looking analysis is intended to provide guidance to funders, drug developers, and researchers, and to accelerate access for children to the best HIV drugs and formulations.