Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV.

OBJECTIVES: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority. METHODS: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens. RESULTS: The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV. CONCLUSIONS: South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals.

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.

Educational delays among children living with perinatally-acquired HIV in Johannesburg, South Africa.

Little is known about how growing up with HIV impacts educational outcomes in sub-Saharan African children. We evaluated if South African children living with HIV (CLWH) were in the appropriate school grade-for-age compared to uninfected control children. We observed higher rates of not being in the correct grade-for-age in CLWH compared with controls (OR 3.32, 95% CI: 2.07-5.34), adjusted for study site, sex, whether the child's biological father was alive, and caregiver education. Initiation of ART before 6 months of age reduced but did not eliminate this association. Whether these associations are due to biological factors or other social and environmental determinants, and how best to support CLWH to achieve educational goals, warrants further investigation.

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women.

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm3 The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8; P = 0.001). No difference in performance was detected by cadre of health worker (P = 0.113) or between point-of-care versus laboratory-based testing (P = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.

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.

Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial.

BACKGROUND: We previously demonstrated the noninferiority of switching to efavirenz (EFV) versus remaining on ritonavir-boosted lopinavir (LPV/r) for virologic control in children infected with human immunodeficiency virus (HIV) and exposed to nevirapine (NVP) for prevention of mother-to-child transmission. Here we assess outcomes up to 4 years post-randomization. METHODS: From 2010-2013, 298 NVP-exposed HIV-infected children ≥3 years of age were randomized to switch to EFV or remain on LPV/r in Johannesburg, South Africa (Clinicaltrials.gov NCT01146873). After trial completion, participants were invited to enroll into observational follow-up. We compared HIV RNA levels, CD4 counts and percentages, lipids, and growth across groups through four years post-randomization. RESULTS: HIV RNA levels 51-1000 copies/mL were less frequently observed in the EFV group than the LPV/r group (odds ratio [OR] 0.67, 95% confidence interval [CI]: 0.51-0.88, P = .004), as was HIV RNA >1000 copies/mL (OR 0.52 95% CI: 0.28-0.98, P = .04). The probability of confirmed HIV RNA >1000 copies/mL by 48 months was 0.07 and 0.12 in the EFV and LPV/r groups, respectively (P = .21). Children randomized to EFV had a reduced risk of elevated total cholesterol (OR 0.45 95% CI: 0.27-0.75, P = .002) and a reduced risk of abnormal triglycerides (OR 0.42, 95% CI 0.29-0.62, P < .001). CONCLUSIONS: Our results indicate that the benefits of switching virologically suppressed NVP-exposed HIV-infected children ≥3 years of age from LPV/r to EFV are sustained long-term. This approach has several advantages, including improved palatability, reduced metabolic toxicity, simplified cotreatment for tuberculosis, and preservation of second line options. CLINICAL TRIALS REGISTRATION: NCT01146873.

Extent of disclosure: what perinatally HIV-infected children have been told about their own HIV status.

How and when to disclose a positive HIV diagnosis to an infected child is a complex challenge for caregivers and healthcare workers. With the introduction of antiretroviral therapy, pediatric HIV infection has transitioned from a fatal disease to a lifelong chronic illness, thus increasing the need to address the disclosure process. As HIV-infected children mature, begin to take part in management of their own health care, and potentially initiate HIV-risk behaviors, understanding the nature of their infection becomes essential. Guidelines recommend developmentally appropriate incremental disclosure, and emphasize full disclosure to school-age children. However, studies from Sub-Saharan Africa report that disclosure to HIV-infected children is often delayed. Between 2013 and 2014, 553 perinatally HIV-infected children aged 4-9 years were enrolled into a cohort study in Johannesburg, South Africa. We assessed the extent of disclosure among these children and evaluated characteristics associated with disclosure. No children aged 4 years had been told their status, while 4% of those aged 5 years, and 8%, 13%, 16%, and 15% of those aged 6, 7, 8, and 9 years, respectively, had been told their status. Age was the strongest predictor of full disclosure (odds ratio 1.6 per year, p = .001). An adult living in the household who was unaware of the child's status was associated with a reduced probability of disclosure, and knowing that someone at the child's school was aware of child's status was associated with an increased probability of disclosure. Among caregivers who had not disclosed, 42% reported ever discussing illness in general with the child, and 17% reported ongoing conversations about illness or HIV. In conclusion, a small minority of school-age children had received full disclosure. Caregivers and healthcare workers require additional support to address disclosure. A broader public health strategy integrating the disclosure process into pediatric HIV treatment programs is recommended.

Dietary Inadequacies in HIV-infected and Uninfected School-aged Children in Johannesburg, South Africa.

OBJECTIVES: The World Health Organization recommends that human immunodeficiency virus (HIV)-infected children increase energy intake and maintain a balanced macronutrient distribution for optimal growth and nutrition. Few studies have evaluated dietary intake of HIV-infected children in resource-limited settings. METHODS: We conducted a cross-sectional analysis of the dietary intake of 220 perinatally HIV-infected children and 220 HIV-uninfected controls ages 5 to 9 years in Johannesburg, South Africa. A standardized 24-hour recall questionnaire and software developed specifically for the South African population were used to estimate intake of energy, macronutrients, and micronutrients. Intake was categorized based on recommendations by the World Health Organization and Acceptable Macronutrient Distribution Ranges established by the IOM. RESULTS: The overall mean age was 6.7 years and 51.8% were boys. Total energy intake was higher in HIV-infected than HIV-uninfected children (1341 vs 1196 kcal/day, P = 0.002), but proportions below the recommended energy requirement were similar in the 2 groups (82.5% vs 85.2%, P = 0.45). Overall, 51.8% of the macronutrient energy intake was from carbohydrates, 13.2% from protein, and 30.8% from fat. The HIV-infected group had a higher percentage of their energy intake from carbohydrates and lower percentage from protein compared with the HIV-uninfected group. Intakes of folate, vitamin A, vitamin D, calcium, iodine, and selenium were suboptimal for both groups. CONCLUSIONS: Our findings suggest that the typical diet of HIV-infected children and uninfected children in Johannesburg, South Africa, does not meet energy or micronutrient requirements. There appear to be opportunities for interventions to improve dietary intake for both groups.

Enhancing HIV Treatment Access and Outcomes Amongst HIV Infected Children and Adolescents in Resource Limited Settings.

Introduction Increasing access to HIV-related care and treatment for children aged 0-18 years in resource-limited settings is an urgent global priority. In 2011-2012 the percentage increase in children accessing antiretroviral therapy was approximately half that of adults (11 vs. 21 %). We propose a model for increasing access to, and retention in, paediatric HIV care and treatment in resource-limited settings. Methods Following a rapid appraisal of recent literature seven main challenges in paediatric HIV-related care and treatment were identified: (1) lack of regular, integrated, ongoing HIV-related diagnosis; (2) weak facility-based systems for tracking and retention in care; (3) interrupted availability of dried blood spot cards (expiration/stock outs); (4) poor quality control of rapid HIV testing; (5) supply-related gaps at health facility-laboratory interface; (6) poor uptake of HIV testing, possibly relating to a fatalistic belief about HIV infection; (7) community-associated reasons e.g. non-disclosure and weak systems for social support, resulting in poor retention in care. Results To increase sustained access to paediatric HIV-related care and treatment, regular updating of Policies, review of inter-sectoral Plans (at facility and community levels) and evaluation of Programme implementation and impact (at national, subnational, facility and community levels) are non-negotiable critical elements. Additionally we recommend the intensified implementation of seven main interventions: (1) update or refresher messaging for health care staff and simple messaging for key staff at early childhood development centres and schools; (2) contact tracing, disclosure and retention monitoring; (3) paying particular attention to infant dried blood spot (DBS) stock control; (4) regular quality assurance of rapid HIV testing procedures; (5) workshops/meetings/dialogues between health facilities and laboratories to resolve transport-related gaps and to facilitate return of results to facilities; (6) community leader and health worker advocacy at creches, schools, religious centres to increase uptake of HIV testing and dispel fatalistic beliefs about HIV; (7) use of mobile communication technology (m-health) and peer/community supporters to maintain contact with patients. Discussion and Conclusion We propose that this package of facility, community and family-orientated interventions are needed to change the trajectory of the paediatric HIV epidemic and its associated patterns of morbidity and mortality, thus achieving the double dividend of improving HIV-free survival.

Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.

Protease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV-1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicativein vitroassay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of thegaggene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of this drug in pediatric patients.

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.

Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation.

BACKGROUND: Efavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children. CASE PRESENTATION: Four black African children, between the ages of 4 and 8 years presenting between 1 and 20 months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60 mg/L, 5-15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation. CONCLUSION: Efavirenz toxicity should always be considered in human immunodeficiency virus-infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate.

"I get hungry all the time": experiences of poverty and pregnancy in an urban healthcare setting in South Africa.

BACKGROUND: For pregnancy to result in a healthy mother and infant, women require adequate nutrition and to be able to access antenatal care, both of which require finances. While most women working in the formal sector in South Africa obtain some form of maternity leave, unemployed women receive no such support. Additional interventions in the form of expanded social assistance to vulnerable pregnant women are needed. To help inform such an approach, we undertook a series of qualitative interviews with low-income pregnant women in Johannesburg. METHODS: Qualitative, in-depth interviews were held with 22 pregnant women at a public sector antenatal clinic in Johannesburg in 2011 to gather data on their greatest needs and priorities during pregnancy, their access to financial resources to meet these needs, and the overall experience of poverty while pregnant. RESULTS: A total of 22 women were interviewed, 5 of whom were primagravid. One woman was in the first trimester of pregnancy, while nine were almost full-term. All but one of the pregnancies were unplanned. Most participants (15/22) were unemployed, two were employed and on paid maternity leave, and the remaining five doing casual, part-time work. In most cases, pregnancy reduced participants' earning potential and heightened reliance on their partners. Women not living with the father of their children generally received erratic financial support from them. The highest monthly expenses mentioned were food, accommodation and transport costs, and shortfalls in all three were reportedly common. Some participants described insufficient food in the household, and expressed concern about whether they were meeting the additional dietary requirements of pregnancy. Preparing for the arrival of a new baby was also a considerable source of anxiety, and was prioritized even above meeting women's own basic needs. CONCLUSIONS: Though pregnancy is a normal life occurrence, it has the potential to further marginalise women and children living in already vulnerable households. Extending the Child Support Grant to include the period of pregnancy would not only serve to acknowledge and address the particular challenges faced by poor women, but also go some way to securing the health of newborn children and future generations.

Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial.

IMPORTANCE: Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission. OBJECTIVE: To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization. INTERVENTIONS: Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148). MAIN OUTCOMES AND MEASURES: Risk difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points. RESULTS: The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to ∞) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to ∞). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group. CONCLUSIONS AND RELEVANCE: Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01146873.

The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants.

The aim of this study was to compare the neurodevelopment of HIV-infected (HI) infants in combination with antiretroviral therapy also known as HAART (highly active antiretroviral therapy) to HIV-exposed uninfected (HEU) infants. Twenty-seven HIV infected and 29 HEU infants under the age of one year attending the Empilweni Clinic at Rahima Moosa Mother and Child Hospital were studied. HI infants were assessed prior to initiating HAART and then for six months whilst on HAART. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, 3rd ed (Bayley III). The HI infants scored significantly lower when compared to HEU infants for motor and language development at baseline, three months and six months follow up. No significant improvement in language (p = 0.46) and motor function (p = 0.91) occurred over time; however, developmental scores did not decrease. Cognitive development in the HI group was significantly lower when compared to the HEU group at visit one (p = 0.003). By six months follow-up, there were no significant differences between the two groups for cognitive development (p = 0.18). This study suggests that HIV-positive infants are delayed when compared to HEU infants. HAART may help to prevent further delay; however, it does not reverse the neurological damage already present. There is a need for therapists to be involved in pediatric HIV clinical services in order to provide early developmental screening as well as rehabilitative services to those children in need.

Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment.

BACKGROUND: While studies of HIV-infected adults on antiretroviral treatment (ART) report no sex differences in immune recovery and virologic response but more ART-associated complications in women, sex differences in disease progression and response to ART among children have not been well assessed. The objective of this study was to evaluate for sex differences in response to ART in South African HIV-infected children who were randomized to continue ritonavir-boosted lopinavir (LPV/r)-based ART or switch to nevirapine-based ART. METHODS: ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005-2010 were compared. Children initiated ritonavir-boosted lopinavir (LPV/r)-based ART before 24 months of age and were randomized to remain on LPV/r or switch to nevirapine-based ART after achieving viral suppression. Children were followed for 76 weeks post-randomization and then long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. Viral load, CD4 count, lipids, anthropometrics, drug concentrations, and adherence were measured at regular intervals. Outcomes were compared between sexes within treatment strata. RESULTS: A total of 323 children (median age 8.8 months, IQR 5.1-13.5), including 168 boys and 155 girls, initiated LPV/r-based ART and 195 children were randomized. No sex differences in risk of virological failure (confirmed viral load >1000 copies/mL) by 156 weeks post-randomization were observed within either treatment group. Girls switched to nevirapine had more robust CD4 count improvement relative to boys in this group through 112 weeks post-randomization. In addition, girls remaining on LPV/r had higher plasma concentrations of ritonavir than boys during post-randomization visits. After a mean of 3.4 years post-randomization, girls remaining on LPV/r also had a higher total cholesterol:HDL ratio and lower mean HDL than boys on LPV/r. CONCLUSIONS: Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen. Future studies are warranted to determine biological mechanisms and clinical significance of these differences. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00117728.

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.

mHealth app usage amongst paediatric department doctors in South Africa.

Background: Smartphone and mobile health (mHealth) applications (apps) have become an integral part of the day-to-day function of healthcare professionals, allowing quick, comprehensive, and up-to-date access to current clinical guidelines and other reference material. Objective: To evaluate the extent and nature of use of mHealth apps by paediatric department doctors in South Africa. Methods: E-mails requesting study participation were sent out to 285 paediatric department doctors employed at six hospitals affiliated to the University of the Witwatersrand. Willing participants were directed to complete the online study questionnaire. Results: A total of 150 respondents completed the questionnaire. All respondents owned a mobile device and already had one or more mHealth apps, 95.3% were unaware of any regulatory body responsible for regulating the use of mHealth apps, 86.0% did not have access to free Wi-Fi at work and 87.3% used an mHealth app at least once daily. Drug dosing (81.3%), diagnostic (59.3%) and clinical decision-making (44.7%) apps were the most common app categories with Medscape® (62.0%) and EMGuidance® (41.3%) being the most frequently used apps. Peer recommendation (76.0%), app credibility (74.0%) and app functionality (66.0%) were the most common factors that were considered by respondents prior to downloading or using an mHealth app. Conclusion: Medical apps are frequently used among paediatric medical doctors of all ranks. Drug dosing, diagnostic and clinical decision-making apps are the most common app categories in use. Improved awareness of the regulations pertaining to the use of mHealth apps amongst doctors is required.

Providing HIV Prevention of Mother to Child Transmission (PMTCT) Services to Migrants During the COVID-19 Pandemic in South Africa: Insights of Healthcare Providers.

BACKGROUND: In March 2020, COVID-19 entered South Africa, resulting in 2.9 million cases, the country took preventative and precautionary measures to control the spread of COVID-19 infection. These measures limited population mobility especially for migrant women living with HIV (WLWH) and the provision of PMTCT services. The purpose of this research was to explore the challenges of the COVID-19 pandemic on PMTCT provision by healthcare providers and understand what strategies could be implemented with lifelong antiretroviral therapy (ART) for migrants to better manage the program. METHODS: Twelve in-depth interviews were conducted with healthcare providers across city and provincial levels on how the changes to the healthcare system with COVID-19 affected highly mobile patients' adherence and utilization of PMTCT services. A thematic content analysis was used for emerging themes and guided by The Utilization of PMTCT Services conceptual framework. RESULTS: Five main themes emerged: (1) Facilitators and barriers to adherence, which included the need for multi-month dispensing for the long term supply of antiretrovirals (ARVs) and the fear of contracting COVID-19 at the hospital that disrupted patients' continuum of care; (2) Healthcare providers work environment, where participants felt overwhelmed with the high patient demand and the lack of infrastructural resources to follow social distancing protocols; (3) Financial challenges and opportunity costs, PMTCT proved difficult for migrants due to border closures and documentation required to receive care, this resulted in treatment interruption and left many unable to receive support at the facility due to capacity restrictions; (4) Interpersonal interactions, mistreatment, and xenophobic attitudes existed toward the migrant HIV population; and (5) "Program sustainability" revealed three key areas for strengthening: longer duration of time allocated with counseling for same-day initiation, the increased use of technology, and translation services for migrants. CONCLUSIONS: It is important to take what was learned during the pandemic and integrate it into routine service delivery, which includes long-term medication supply to reduce risk with multiple visits to collect medication, and the use of technology to alleviate the high-burden of patient demand. Healthcare policies that work toward inclusion and sustainability for migrants are needed to improve the integration of safer and practical methods of PMTCT provision into health systems.