Prevalence of dyslipidaemia in HIV-infected children and adolescents treated with protease inhibitors

Background – HIV infection and antiretroviral therapy (ART) are associated with dyslipidaemia in children. Protease inhibitor (PI) based regimens, in particular, have shown the highest association. Methods – We conducted a retrospective study of children treated with either a first- or second-line lopinavir/ritonavir (LPV/r) regimen who had any lipid tests done from 2004 to 2015. Dyslipidaemia was defined as hypercholesterolaemia [total cholesterol ≥5.13mmol/l (≥200mg/dl)] and /or hypertriglyceridaemia [total triglycerides ≥1.69 mmol/l (≥150mg/dl)]. There were 4 cross sectional points of analysis in this study: ART start, LPV/r-start, 12 and 24 months after starting LPV/r. Demographic and clinical characteristics were compared using univariate and multivariate analyses to determine risk factors for dyslipidaemia at each time point using logistic regression to obtain odds ratios and 95% confidence intervals (95% CI). Results - Few children had lipids measured over the follow-up period, increasing from 7% (146/2145) at ART initiation to 24% (365/1522) after 24 months on LPV/r. The median age at ART-start was 1.6 (0.4; 4.4) increasing to 3.6 (2.6; 6.2) years by 24 months. The majority (51%) of the children had severe immune suppression at ART-start. The prevalence of dyslipidaemia at ART-start was 47%, decreasing to 36% at 24 months. Multivariate analysis at 12 months found that children less than 10 years of age with near suppressed viral loads (viral load < 4 logs) were more likely to have dyslipidaemia. At 24 months on LPV/r, ART duration greater than 60 months and high viral loads were protective factors. Conclusion – The high prevalence of dyslipidaemia in young children is concerning as lopinavir/ritonavir is the mainstay of ART in young children for the foreseeable future.XL201

Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.

BACKGROUND WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited. METHODS We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg. RESULTS Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (p = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2). CONCLUSION Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg

Virologic response to efavirenz-based first-line antiretroviral therapy in children with previous exposure to antiretrovirals to prevent mother-to-child transmission

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6–18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11)

Outcomes in treatment with darunavir/ritonavir in ART-experienced paediatric patients

Increasing development of resistant mutations to first- and second-line antiretroviral (ART) regimens among chil- dren is a matter of concern, as limited third-line paediatric ART preparations are available in the public sector.

Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa

Background: Ninety percent of the world&#x0027;s 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed. Objective: The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year. Methods: The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children&#x0027;s Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively. Results: The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1&#x2013;8.8). In the first 12 months on ART, independent predictors of LTFU were age &#60;1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ &#x2264; &#x2212;2). Among children still on treatment at 1 year from ART initiation, characteristics that predicted LTFU within the second year were recent year of ART start, mother as a primary caregiver, being underweight (WAZ &#x2264; &#x2212;2), and low CD4 cell percentage. Conclusions: There are similarities between the known predictors of death and the predictors of LTFU in the first and second years of ART. Knowing the vital status of children is important to determine LTFU. Although HIV-positive children cared for by their mothers appear to be at greater risk of becoming LTFU, further research is needed to explore the challenges faced by mothers and other caregivers and their impact on long-term HIV care. There is also a need to investigate the effects of differential access to ART between mothers and children and its impact on ART outcomes in children

Virologic non-suppression and early loss to follow up among pregnant and non-pregnant adolescents aged 15-19 years initiating antiretroviral therapy in South Africa: a retrospective cohort study.

INTRODUCTION Older adolescents aged 15-19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non-suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa. METHODS We included adolescents aged 15-19 years initiating ART between 2004 and 2019, with ≥ one viral load (VL) measurement between 4 and 24.5 months, and ≥ 6 months follow-up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA). We defined VNS as VL ≥400 copies/ml and LTFU as not being in care for ≥180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART. We examined factors associated with VNS and LTFU using Fine&Gray competing risk models. RESULTS We included a total of 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24-month follow-up, 424 (15.5%) of all adolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/μl at ART initiation among all adolescents having adjusted for all measured patient characteristics [adjusted sub-distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. ≤200 cells/μl: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/μl were risk factors for LTFU among all adolescents. CONCLUSIONS Older adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent-friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

INTRODUCTION The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count 1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. RESULTS Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa

What Should we do When HIV-Positive Children Fail First-Line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

BACKGROUND Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence and the development of HIV resistance mutations. We aimed to evaluate four management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. METHODS We included children (aged <16 years) with VF from 8 IeDEA-SA cohorts, initiating cART between 2004-2010, who followed one of four management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. RESULTS 982 patients were followed over 54168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% CI 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI -2.0, -0.8), whilst switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI -12.1, 1.3) and -5.6% (95% CI -15.4, 4.1)) and virologic outcomes (0.2 (95% CI -3.6, 4.1) and 0.8 (95% CI -0.6, 2.1) respectively. CONCLUSIONS The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies