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.

Point-of-care viral load testing among adolescents and young adults living with HIV in Haiti: a randomized control trial.

HIV viral load (VL) monitoring can reinforce antiretroviral therapy (ART) adherence. Standard VL testing requires high laboratory capacity and coordination between clinic and laboratory which can delay results. A randomized trial comparing point-of-care (POC) VL testing to standard VL testing among 150 adolescents and young adults, ages 10-24 years, living with HIV in Haiti determined if POC VL testing could return faster results and improve ART adherence and viral suppression. Participants received a POC VL test with same-day result (POC arm) or a standard VL test with result given 1 month later (SOC arm). POC arm participants were more likely to receive a test result within 6 weeks than SOC arm participants (94.7% vs. 80.1%; p1000 copies/ml and low self-reported ART adherence was stronger in the POC arm (OR: 6.57; 95%CI: 2.12-25.21) than the SOC arm (OR: 2.62; 95%CI: 0.97-7.44) suggesting more accurate self-report in the POC arm. POC VL testing was effectively implemented in this low-resource setting with faster results and is a pragmatic intervention that may enable clinicians to identify those with high VL to provide enhanced counseling or regimen changes sooner.Trial registration: ClinicalTrials.gov identifier: NCT03288246.

Point-of-care viral load testing among adolescents and youth living with HIV in Haiti: a protocol for a randomised trial to evaluate implementation and effect.

INTRODUCTION: Adolescents living with HIV have poor antiretroviral therapy (ART) adherence and viral suppression outcomes. Viral load (VL) monitoring could reinforce adherence but standard VL testing requires strong laboratory capacity often only available in large central laboratories. Thus, coordinated transport of samples and results between the clinic and laboratory is required, presenting opportunities for delayed or misplaced results. Newly available point-of-care (POC) VL testing systems return test results the same day and could simplify VL monitoring so that adolescents receive test results faster which could strengthen adherence counselling and improve ART adherence and viral suppression. METHODS AND ANALYSIS: This non-blinded randomised clinical trial is designed to evaluate the implementation and effectiveness of POC VL testing compared with standard laboratory-based VL testing among adolescents and youth living with HIV in Haiti. A total of 150 participants ages 10-24 who have been on ART for >6 months are randomised 1:1 to intervention or standard arms. Intervention arm participants receive a POC VL test (Cepheid Xpert HIV-1 Viral Load system) with same-day result and immediate ART adherence counselling. Standard care participants receive a laboratory-based VL test (Abbott m2000sp/m2000rt) with the result available 1 month later, at which time they receive ART adherence counselling. VL testing is repeated 6 months later for both arms. The primary objective is to describe the implementation of POC VL testing compared with standard laboratory-based VL testing. The secondary objective is to evaluate the effect of POC VL testing on VL suppression at 6 months and participant comprehension of the correlation between VL and ART adherence. ETHICS AND DISSEMINATION: This study is approved by GHESKIO, Weill Cornell Medicine and Columbia University ethics committees. This trial will provide critical data to understand if and how POC VL testing may impact adolescent ART adherence and viral suppression. If effective, POC VL testing could routinely supplement standard laboratory-based VL testing among high-risk populations living with HIV. TRIAL REGISTRATION NUMBER: NCT03288246.

Behavioral Functioning and Quality of Life in South African Children Living with HIV on Antiretroviral Therapy.

This study examined behavioral functioning and quality of life in South African children living with perinatally acquired HIV. Compared with controls, children living with perinatally acquired HIV had a higher mean total difficulties score assessed by the Strengths and Difficulties Questionnaire and lower mean quality of life scores assessed by the Pediatric Quality of Life Inventory.

Bone Quality Measured Using Calcaneal Quantitative Ultrasonography Is Reduced Among Children with HIV in Johannesburg, South Africa.

We evaluated bone quality among South African children with HIV over a 2-year period by quantitative ultrasound (QUS). Children with HIV have persistently lower bone quality compared with controls reflecting increased porosity, reduced strength, and possibly an increased short- and long-term risk of fracture.

Decreased Vigorous Physical Activity in School-Aged Children with Human Immunodeficiency Virus in Johannesburg, South Africa.

OBJECTIVE: To describe physical activity in South African children with and without HIV. STUDY DESIGN: Study measurements were obtained in 218 children with perinatal HIV and 180 children without HIV aged 5-9 years in a study conducted in Johannesburg, South Africa. Weight-for-age z-score, height-for-age z-score, frequency and duration of moderate and vigorous physical activity, and sedentary behaviors were obtained. These measurements were compared between children with and without HIV. RESULTS: Weight-for-age z-score and height-for-age z-score were significantly lower for children with HIV compared with those without HIV. Among children who attended school, fewer children with HIV than children without HIV participated in physical education (41% vs 64%; P = .0003) and organized after-school sports (38% vs 64%; P < .001). The proportion of children in both groups meeting World Health Organization recommendations for physical activity was similar (84% overall); however, girls with HIV spent less time in vigorous physical activity than girls without HIV (420 vs 780 minutes/week; P = .001). This difference remained significant even when girls with a medical condition with the potential to limit physical activity were excluded, and after adjusting for age. Time spent in sedentary behaviors did not differ significantly between the two groups. CONCLUSION: Although children with HIV with well-controlled disease after initiating antiretroviral therapy early in life achieve high levels of physical activity, vigorous physical activity is lower in girls with HIV than in healthy controls. This finding may reflect lower participation in school-based physical education and organized after-school physical activity.

Initiation of antiretroviral therapy before 6 months of age is associated with faster growth recovery in South African children perinatally infected with human immunodeficiency virus.

OBJECTIVE: To describe the effects of age at antiretroviral therapy (ART) initiation on growth outcomes among children infected with HIV followed for 48 months after treatment initiation. STUDY DESIGN: This secondary analysis describes anthropometric changes in children infected with HIV in Johannesburg, South Africa who initiated ritonavir-boosted lopinavir-based ART before 24 months of age and were randomized to continue ritonavir-boosted lopinavir or to receive nevirapine after achieving and maintaining virologic suppression. Weight, height, and head circumference were measured at visits over 48 months post-ART initiation. Growth patterns including weight-for-age z-scores (WAZs), height-for-age z-scores, body mass index-for-age z-scores, and head circumference for age z-score were compared between children initiating ART<6 months, 6-12 months, and 12-24 months of age. RESULTS: A total of 195 children (mean±SD age 10.7±5.9 months), including 54 (27.7%)<6 months, 69 (35.4%) 6-12 months, and 72 (36.9%) 12-24 months of age at ART initiation, were evaluated. In the first 12 months on treatment, children<6 months of age at ART initiation experienced more rapid improvement in WAZ (1.98 vs 1.44, P=.084) and head circumference for age z-score (1.24 vs 0.45, P=.004) than children who initiated ART between 12-24 months of age. By 48 months on ART, growth outcomes were similar, regardless of age at ART initiation. WAZ approached population norms by 12 months on ART. Although improving, height-for-age z-scores remained on average 1.0 z-score below population norms at 48 months of therapy. CONCLUSIONS: Initiation of ART before 6 months of age results in more rapid growth recovery in children infected with HIV. These data provide further evidence for the importance of prompt diagnosis and early initiation of ART for infants infected with HIV.

Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.

BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. SUBJECTS: The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. METHODS: One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/m(2) or 300/75 mg/m(2) lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. RESULTS: All subjects were escalated to the 300/75 mg/m(2) twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/ml at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/mm(3); 10.3%) and ARV-experienced subjects (284 cells/mm(3); 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. CONCLUSIONS: The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.