Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

BACKGROUND: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. METHODS: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m2) with HIV-1 on daily oral ART were enrolled at 15 centres in four countries (Botswana, South Africa, Thailand, and the USA). After 4-6 weeks of oral cabotegravir (cohort 1C) or rilpivirine (cohort 1R), participants received intramuscular long-acting cabotegravir or long-acting rilpivirine every 4 weeks or 8 weeks per the adult dosing regimens, while continuing pre-study ART. The primary outcomes were assessments of safety measures, including all adverse events, until week 4 for oral cabotegravir and until week 16 for long-acting cabotegravir and long-acting rilpivirine, and pharmacokinetic measures, including the area under the plasma concentration versus time curve during the dosing interval (AUC0-tau) and drug concentrations, at week 2 for oral dosing of cabotegravir and at week 16 for intramuscular dosing of cabotegravir and rilpivirine. Enrolment into cohort 1C or cohort 1R was based on the participant's pre-study ART, meaning that masking was not done. For pharmacokinetic analyses, blood samples were drawn at weeks 2-4 after oral dosing and weeks 4-16 after intramuscular dosing. Safety outcome measures were summarised using frequencies, percentages, and exact 95% CIs; pharmacokinetic parameters were summarised using descriptive statistics. This trial is registered at ClinicalTrials.gov, NCT03497676, and is closed to enrolment. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC0-tau was 148·5 (range 37·2-433·1) µg·h/mL. The week 16 median concentrations for the every-4-weeks and every-8-weeks dosing was 3·11 µg/mL (range 1·22-6·19) and 1·15 µg/mL (<0·025-5·29) for cabotegravir and 52·9 ng/mL (31·9-148·0) and 39·1 ng/mL (27·2-81·3) for rilpivirine, respectively. These concentrations were similar to those in adults. INTERPRETATION: Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. FUNDING: The National Institutes of Health and ViiV Healthcare.

Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.

Incidence of non-AIDS defining comorbidities among young adults with perinatally-acquired HIV in North America, 2000-2019.

OBJECTIVE: To describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally-acquired HIV (PHIV) aged 18 to 30. DESIGN: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated overall, sex-, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression. T2DM was defined as glycosylated hemoglobin >6.5% or based on clinical diagnosis and medication use. Hypercholesterolemia was based on medication use or total cholesterol ≥200 mg/dL. Hypertriglyceridemia was based on medication use or fasting triglyceride ≥150 mg/dL or non-fasting ≥200 mg/dL. Hypertension was based on clinical diagnosis. CKD was defined as estimated glomerular filtration rates <90 ml/mi|1.73 m2 for ≥3 months. RESULTS: Cumulative incidence by age 30 and incidence rates from age 18 to 30 (per 100 person-years) were: T2DM: 19%, 2.9; hypercholesterolemia: 40%, 4.6; hypertriglyceridemia: 50%, 5.6; hypertension: 22%, 2.0; and CKD: 25%, 3.3. Non-Black females had the highest incidence of hypercholesterolemia and hypertriglyceridemia, Black adults had the highest hypertension incidence, and Black males had the highest CKD incidence. CONCLUSION: There was a high incidence of five chronic comorbidities among people with PHIV. Earlier screening at younger ages might be considered for this unique population to strengthen prevention strategies and initiate treatment in a timely way.

Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

Advancing Adolescent and Young Adult HIV Prevention and Care and Treatment Through Use of Multi-level Theories and Frameworks: A Scoping Review and Adapted HIV Ecological Framework.

While multi-level theories and frameworks have become a cornerstone in broader efforts to address HIV inequities, little is known regarding their application in adolescent and young adult (AYA) HIV research. To address this gap, we conducted a scoping review to assess the use and application of multi-level theories and frameworks in AYA HIV prevention and care and treatment empirical research. We systematically searched five databases for articles published between 2010 and May 2020, screened abstracts, and reviewed eligible full-text articles for inclusion. Of the 5890 citations identified, 1706 underwent full-text review and 88 met the inclusion criteria: 70 focused on HIV prevention, with only 14 on care and treatment, 2 on both HIV prevention and care and treatment, and 2 on HIV-affected AYA. Most authors described the theory-based multi-level framework as informing their data analysis, with only 12 describing it as informing/guiding an intervention. More than seventy different multi-level theories were described, with 38% utilizing socio-ecological models or the eco-developmental theory. Findings were used to inform the adaptation of an AYA World Health Organization multi-level framework specifically to guide AYA HIV research.

In Support of Breast/Chest Feeding by People with HIV in High-Income Settings.

Given that HIV can be transmitted through breastfeeding, historically, breastfeeding among women with HIV in the United States and other resource rich settings was actively discouraged. Formula feeding was mandated as the only feeding option primarily out of concern for breastmilk transmission of HIV, which occurred in 16-24%1-3 of cases pre-antiretroviral therapy (ART) use. In January 2023, the United States' Department of Health and Human Services (DHHS) Perinatal Guidelines were updated to support shared decision making for infant feeding choices4. Updated data from clinical trials in low- and middle-income settings suggest that the actual rate of HIV transmission through breastmilk in the context of maternal ART or neonatal post-exposure prophylaxis (PEP) is 0.3-1%1-3. High income countries are reporting increasing numbers of people with HIV breastfeeding their infants without cases of HIV transmission to date5-10. Here we will present the reasons for fully embracing breast/chestfeeding as a viable and safe infant feeding option for HIV-exposed infants in high-income settings now, while acknowledging unanswered questions and the need to continually craft more nuanced clinical guidance.

Projecting the Clinical and Economic Impacts of Changes to HIV Care Among Adolescents and Young Adults in the United States: Lessons From the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, many US youth with HIV (YHIV) used telehealth services; others experienced disruptions in clinic and antiretroviral therapy (ART) access. METHODS: Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent HIV microsimulation model, we evaluated 3 scenarios: 1) Clinic: in-person care; 2) Telehealth: virtual visits, without CD4 or viral load monitoring for 12 months, followed by return to usual care; and 3) Interruption: complete care interruption with no ART access or laboratory monitoring for 6 months (maximum clinic closure time), followed by return to usual care for 80%. We assigned higher 1-year retention (87% vs 80%) and lower cost/visit ($49 vs $56) for Telehealth vs Clinic. We modeled 2 YHIV cohorts with non-perinatal (YNPHIV) and perinatal (YPHIV) HIV, which differed by mean age (22 vs 16 years), sex at birth (85% vs 47% male), starting CD4 count (527/µL vs 635/µL), ART, mortality, and HIV-related costs. We projected life months (LMs) and costs/100 YHIV over 10 years. RESULTS: Over 10 years, LMs in Clinic and Telehealth would be similar (YNPHIV: 11 350 vs 11 360 LMs; YPHIV: 11 680 LMs for both strategies); costs would be $0.3M (YNPHIV) and $0.4M (YPHIV) more for Telehealth than Clinic. Interruption would be less effective (YNPHIV: 11 230 LMs; YPHIV: 11 620 LMs) and less costly (YNPHIV: $1.3M less; YPHIV: $0.2M less) than Clinic. Higher retention in Telehealth led to increased ART use and thus higher costs. CONCLUSIONS: Telehealth could be as effective as in-person care for some YHIV, at slightly increased cost. Short interruptions to ART and laboratory monitoring may have negative long-term clinical implications.

Patient Portal Privacy: Perspectives of Adolescents and Emerging Adults Living with HIV and the Parental/Guardian Role in Supporting Their Care.

BACKGROUND: Increasing the percentage of people living with human immunodeficiency virus (HIV), including youth, who are virally suppressed to 95% is an overall goal of the ending the HIV epidemic initiative. While patient portals have become ubiquitous, questions remain about how best to operationalize parental/guardian access to youth's patient portals in alignment with optimizing HIV care outcomes and patient preferences. This qualitative study focuses on understanding perspectives among youth with HIV (YHIV) about parental access to patient portals. METHODS: Eligible participants were YHIV aged 13 to 25 years receiving care at an urban academic hospital. Semistructured individual/paired interviews were conducted between May 2022 and March 2023. Participants were asked to discuss thoughts on parental access to patient portals, and roles parents/guardians have in supporting their HIV care. Semistructured interviews were conducted with adolescent and emerging adult health care workers (HCWs) to gain perspectives on YHIV emergent themes. Audio-recorded interviews were transcribed verbatim, and we conducted thematic analysis using an inductive approach to identify codes and themes. RESULTS: Sixteen YHIV and four HCWs participated in interviews. Parental roles in coordinating HIV care ranged from supporting YHIV needs for transportation, acquiring, and taking medications, to not having any role at all. Participants shared heterogeneous perspectives about their openness to share patient portal access with their parents/guardians. Perspectives were not strictly congruent along lines of participant age or parental roles in helping youth to manage HIV care. Sharing passwords emerged both as a pathway that YHIV grant access to their accounts and a source of confusion for clinicians when parents/guardians send messages using their child's account. CONCLUSION: Findings suggest HCWs should initiate conversations with YHIV patients to determine preferences for parental/guardian access to their patient portal, educate on proxy access, and explain the extent of medical information that is shared with proxy accounts, regardless of age and perceived parental involvement in HIV care.

Infant feeding for people living with HIV in high resource settings: a multi-disciplinary approach with best practices to maximise risk reduction.

Shared decision making for infant feeding in the context of HIV in high-resourced settings is necessary to acknowledge patient autonomy, meet increasing patient requests and address the changing reality of perinatal HIV care. In low-to middle-income countries (LMIC), where the majority of individuals living with HIV reside, persons with HIV are recommended to breastfeed their infants. In the setting of maternal anti-retroviral therapy (ART) use throughout pregnancy, viral suppression and appropriate neonatal post-exposure prophylaxis (PEP) use, updated information indicates that the risk of HIV transmission through breastmilk may be between 0.3 and 1%. While not endorsing or recommending breastfeeding, the United States' DHHS perinatal guidelines are similarly pivoting, stating that individuals should "receive patient-centred, evidence-based counselling on infant feeding options." Similar statements appear in the British, Canadian, Swiss, European, and Australasian perinatal guidelines. We assembled a multi-disciplinary group at our institution to develop a structured shared decision-making process and protocol for successful implementation of breastfeeding. We recommend early and frequent counselling about infant feeding options, which should include well known benefits of breastfeeding even in the context of HIV and the individual's medical and psychosocial circumstances, with respect and support for patient's autonomy in choosing their infant feeding option.

Immune activation and exhaustion marker expression on T-cell subsets in ART-treated adolescents and young adults with perinatal HIV-1 infection as correlates of viral persistence.

HIV-1 infection in memory CD4+ T cells forms a latent reservoir that is a barrier to cure. Identification of immune biomarkers that correlate with HIV-1 reservoir size may aid with evaluating efficacy of HIV-1 eradication strategies, towards ART-free remission and cure. In adults living with non-perinatal HIV-1, the immune exhaustion marker PD-1 on central memory CD4+ T cells (Tcm) correlates with measures of HIV-1 reservoir size. Immune correlates of HIV-1 are less defined in adolescents and young adults with perinatal HIV-1. With multi-parameter flow cytometry, we examined immune activation (CD69, CD25, HLA-DR), and exhaustion (PD-1, TIGIT, TIM-3 and LAG-3) markers on CD4+ T cell subsets (naïve (Tn), central memory (Tcm), and the combination (Ttem) of transitional (Ttm) and effector memory (Tem) cells, in 10 adolescents and young adults living with perinatal HIV-1 (median age 15.9 years; median duration of virologic suppression 7.0 years), in whom HIV-1 reservoir size was measured with the Intact Proviral HIV-1 DNA Assay (IPDA) and an enhanced Tat/Rev limiting dilution assay (TILDA). RNA-seq was also performed on the unstimulated CD4+ T cells. The median total HIV-1 DNA concentration in memory CD4+ T cells was 211.90 copies per million CD4+ T cells. In the 7 participants with subtype B HIV-1 infection, the median intact proviral DNA load was 7.96 copies per million CD4+ T cells. Levels of HLA-DR and TIGIT on the Ttem were correlated with total HIV-1 DNA (r=0.76, p=0.015) and (r=0.72, p=0.023), respectively, but not with intact proviral load or induced reservoir size. HIV-1 DNA load was also positively correlated with transcriptional clusters associated with HLA-DR expression by RNA-seq. In contrast, PD-1 expression on Tcm was inversely correlated with total HIV-1 DNA (r=-0.67, p=0.039). Reservoir size by IPDA and TILDA were correlated (r=0.81, p=0.036). Thus, in this cohort of youths with long-standing treated perinatal infection, HLA-DR and TIGIT on Ttem were the key correlates of HIV-1 infected cell frequencies by total HIV-1 DNA, and not PD-1. Total HIV-1 DNA was negatively correlated with PD-1 expressing Tcm. These differences in longstanding perinatal HIV-1 infection compared with adult infection requires further study in larger cohorts.

Understanding Perceived Risks and Sexual Behavior Among Adolescents and Young Adults During the COVID-19 Pandemic.

PURPOSE: We sought to describe the relationship between COVID-19 risk perception and sexual behaviors among urban adolescents and young adults (AYA). METHODS: Data were collected from 159 urban AYAs on COVID-19 risk perception, COVID-19 infections and deaths, romantic relationships, and sexual behavior during the stay-at-home order using a telephone survey. RESULTS: Seventy-nine percent of the study participants engaged in sexual intercourse during the stay-at-home order. Only 38% of these used condoms during their last sexual encounter. Experiencing COVID-19 positivity within their social circle was not related to COVID-19 testing. Concern for COVID-19 infection or experiencing a COVID-19 diagnosis or death in one's social circles was not associated with sexual intercourse or condom use. DISCUSSION: Urban AYA remained at risk for sexually transmitted infections, and COVID-19, given high baseline community rates of sexually transmitted infections and COVID-19, low condom use, and low COVID-19 risk perception at the time of the survey.

Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series.

BACKGROUND: Adherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers. However, to date, the approved LAI-ART strategies (e.g., cabotegravir and rilpivirine (CAB/RPV)) have targeted those who have already attained viral suppression, precluding their use in the 40% of adolescents and young adults (AYA) that VS has eluded. CASE PRESENTATION: Ms. X is a 30-year-old woman with perinatally-acquired HIV and barriers to adherence. Despite many interventions, she remained persistently viremic, with resultant immune suppression and multiple comorbid opportunistic conditions, and viral load (VL) > 10,000,000 copies/ml. Given her longstanding history of poor adherence to an oral regimen, a switch to monthly intramuscular (IM) injections and biweekly infusions of ibalizumab were initiated leading to decreased viral load to 8,110 copies/ml within two weeks. Ms. H is a 33-year-old woman with cognitive limitations due to childhood lead poisoning. Her viral load trajectory took a downward turn, precipitated by various life events, remaining elevated despite intensive case management. Initiation of LAI-ART (CAB/RPV) in this patient led to an undetectable VL (< 20 copies/ml) within two months of treatment initiation. Miss Y. is a 37-year-old woman with perinatally-acquired HIV and chronic challenges with nonadherence and longstanding immunosuppression with CD4 < 200 cells/mm3 for > 5 years. She received a 1-month oral lead-in (OLI) of cabotegravir/rilpivirine, followed by the injectable loading dose. She has since adhered to all her monthly dosing appointments, sustained VS, and transitioned to a bi-monthly injection schedule. CONCLUSION: These three individuals with HIV (perinatally and non-perinatally acquired) with longstanding nonadherence and persistent viremia were successfully initiated on LAI-ART through the process of care coordination and the collective efforts of the care team, highlighting the barriers, challenges, and the multidisciplinary coordination needed to assure successful implementation of this strategy for the most vulnerable of patients.

Preventing and diagnosing HIV-related comorbidities in adolescents.

Adolescents with HIV are growing into adulthood and are at risk for comorbidities. Comorbidities in adolescents often go unrecognized, increasing morbidity and mortality, and contributing to poorer outcomes for youth with HIV. Youth with perinatally and nonperinatally acquired HIV are at risk of developing HIV-associated and non-HIV comorbidities, including cardiovascular diseases, diabetes, mental health disorders, renal diseases, and bone disorders. Youth with HIV are also at risk for altered fat distribution and weight gain associated with certain classes of antiretroviral therapy. Sexually transmitted infections from inconsistent condom use pose a sexual health challenge for youth with HIV. Prompt interventions through comprehensive history taking, physical exams, regular screening, and prevention and treatment of clinically evident comorbid conditions are needed to prevent progression and complications.

Coordination of inflammatory responses in children with perinatally acquired HIV infection.

OBJECTIVE: We investigated dynamics of inflammatory biomarkers in children with perinatally acquired HIV (PHIV) who started antiretrovirals at age less than 3 years and achieved sustained virologic control (HIV plasma RNA <400 copies/ml). DESIGN: This was a retrospective analysis of inflammatory biomarkers in children enrolled in a randomized trial of early (<3 years of age) PI-based versus NNRTI-based regimens (P1060), who achieved sustained virologic control and participated in a neurodevelopmental follow-up study (P1104s) between ages 5 and 11 years. METHODS: We measured 20 inflammatory biomarkers using ELISA or chemiluminescence at onset of sustained virologic control (Tc) and at P1104s entry (Te). RESULTS: The 213 participants had median ages of 1.2, 1.9, and 7 years at antiretroviral initiation, Tc, and Te, respectively, with 138 on protease inhibitor-based and 74 on NNRTI-based regimens at Tc. Eighteen markers decreased and two increased from Tc to Te (Te-Tc). Biomarker subsets, particularly cytokines, the chemokine IP-10, and adhesion molecules sICAM-1 and sVCAM-1, correlated at Tc, Te, and Te-Tc. At Tc, higher biomarker levels were associated with younger age, female sex, HIV plasma RNA at least 750 000 copies/ml, lower nadir CD4 + %, lower nadir weight z scores, and NNRTI-based treatment. Greater Te-Tc biomarker declines were associated with younger age, male sex, higher Tc biomarker levels, lower nadir CD4 + %, and NNRTI-based treatment. Duration of controlled viremia and nadir height z scores showed mixed associations. CONCLUSION: Biomarker expression showed substantial coordination. Most markers decreased after virologic control. Demographic and clinical variables associated with biomarker patterns were identified. Mechanistic studies of these biomarker patterns are needed to inform interventions to control inflammation.

Experience and Outcomes of Breastfed Infants of Women Living With HIV in the United States: Findings From a Single-Center Breastfeeding Support Initiative.

We assessed breastfeeding outcomes for a cohort of infants born to women living with HIV (WLHIV) at an urban health care center in the United States. Ten infants were exclusively breastfed for a mean duration of 4.4 (1.0-8.6) months. All had negative HIV RNA PCRs at a median age of 16 months.

Site-Randomized Controlled Trial of a Combined Cognitive Behavioral Therapy and a Medication Management Algorithm for Treatment of Depression Among Youth Living With HIV in the United States.

BACKGROUND: Depression is frequent among youth living with HIV (YLWH). Studies suggest that manualized treatment guided by symptom measurement is more efficacious than usual care. SETTING: This study evaluated manualized, measurement-guided depression treatment among YLWH, aged 12-24 years at 13 US sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network. METHODS: Using restricted randomization, sites were assigned to either a 24-week, combination cognitive behavioral therapy and medication management algorithm (COMB-R) tailored for YLWH or to enhanced standard of care, which provided standard psychotherapy and medication management. Eligibility included diagnosis of nonpsychotic depression and current depressive symptoms. Arm comparisons used t tests on site-level means. RESULTS: Thirteen sites enrolled 156 YLWH, with a median of 13 participants per site (range 2-16). At baseline, there were no significant differences between arms on demographic factors, severity of depression, or HIV status. The average site-level participant characteristics were as follows: mean age of 21 years, 45% male, 61% Black, and 53% acquired HIV through perinatal transmission. At week 24, youth at COMB-R sites, compared with enhanced standard of care sites, reported significantly fewer depressive symptoms on the Quick Inventory for Depression Symptomatology Self-Report (QIDS-SR score 6.7 vs. 10.6, P = 0.01) and a greater proportion in remission (QIDS-SR score ≤ 5; 47.9% vs. 17.0%, P = 0.01). The site mean HIV viral load and CD4 T-cell level were not significantly different between arms at week 24. CONCLUSIONS: A manualized, measurement-guided psychotherapy and medication management algorithm tailored for YLWH significantly reduced depressive symptoms compared with standard care at HIV clinics.

Perinatal Depressive Symptoms, Human Immunodeficiency Virus (HIV) Suppression, and the Underlying Role of Antiretroviral Therapy Adherence: A Longitudinal Mediation Analysis in the IMPAACT P1025 Cohort.

BACKGROUND: Women with HIV have higher risk of depressive symptoms in the perinatal period. Evidence on how perinatal depressive symptoms affect viral suppression (VS) and adherence to antiretroviral therapy (ART) remains limited. METHODS: Perinatal depressive symptoms were assessed using 6 items from the AIDS Clinical Trials Group (ACTG) Quality of Life questionnaire. VS (viral load <400 copies/mL) was the outcome. Adherence was defined as no missed dose in the past 1-4 weeks using the ACTG Adherence Questionnaire. Generalized mixed-effects structural equation models estimated the association of depressive symptoms on VS and the mediating role of ART adherence among women enrolled in the IMPAACT P1025 Perinatal Core Protocol (2002-2013). RESULTS: Among 1869 participants, 47.6% were 21-29 years, 57.6% non-Hispanic Black. In the third trimester, the mean depressive symptoms score was 14.0 (±5.2), 68.0% had consistent adherence, and 77.3% achieved VS. At 6 months postpartum, depressive symptoms declined while adherence and VS fell to 59.8% and 53.0%, respectively. In the fully adjusted model, a 1-SD increase in depressive symptoms was associated with a 3.8-percentage-point (95% CI: -5.7, -1.9) decline in VS. This effect is the sum of the indirect effect of depressive symptoms on VS via ART adherence (-0.4; 95% CI: -.7, -.2) and the direct effect through other pathways (-3.4; -5.2, -1.5). The decline in adherence driven by depressive symptoms accounted for ≥11% of the total negative effect of depressive symptoms on VS. CONCLUSIONS: Perinatal depressive symptoms were associated with decreased adherence and VS, highlighting the need to screen for, diagnose, and treat perinatal depression to optimize maternal outcomes. CLINICAL TRIALS REGISTRATION: NCT00028145.