Search

Abstract Background The Adolescents and Adults Living with Perinatal HIV (AALPHI) study is one of only three cohort studies worldwide evaluating the impact of HIV on young people living with perinatal HIV (PLHIV) relative to a comparable group of HIV negative young people in close relationship with an HIV positive individual, for example, their mother, sibling or partner. This project aimed to engage young people with the AALPHI study findings, help them take ownership, and decide how they would disseminate the key messages to both study participants and to the wider community. Methods In brief, 318 PLHIV and 100 HIV negative adolescents participated in AALPHI, where they each were interviewed twice, around two years apart. They were asked a wide range of psychosocial and risk behaviour questions and their cognitive function was assessed. We invited three AALPHI participants and seven members of the Youth Trials Board at the Children’s HIV Association (CHIVA) to attend up to four workshops. They were provided with the key AALPHI research findings and asked to develop them into a format that was accessible and understandable for young people. Some who had not participated before formed a group in the fourth dissemination workshop that confirmed the most important concepts and results. Results The young people decided to develop a film and a leaflet about the AALPHI findings and co-produced them with a film maker and graphic designer. Challenges included working with the film maker and the venue for the first three dissemination workshops was an office space which was not ideal. Conclusion Engaging young people in the dissemination of the AALPHI findings ensured the results were communicated in a way that was more likely to be relevant, accessible and useful to those affected by the study. This project demonstrates how young people in potentially stigmatised areas of care, such as HIV, can be involved in research dissemination.

Abstract Background Evidence suggests that engagement in care (EIC) may be worse in young people living with perinatal HIV (YPLPHIV) compared to adults or children living with HIV. We took a published EIC algorithm for adults with HIV, which takes patients’ clinical scenarios into account, and adapted it for use in YPLPHIV in England, to measure their EIC. Methods The adult algorithm predicts when in the next 6 months the next clinic visit should be scheduled, based on routinely collected clinical indicators at the current visit. We updated the algorithm based on the latest adult guidelines at the time, and modified it for young people in paediatric care using the latest European paediatric guidelines. Paediatric/adolescent HIV consultants from the UK reviewed and adapted the resulting flowcharts. The adapted algorithm was applied to the Adolescent and Adults Living with Perinatal HIV (AALPHI) cohort in England. Data for 12 months following entry into AALPHI were used to predicted visits which were then compared to appointment attendances, to measure whether young people were in care in each month. Proxy markers (e.g. dates of CD4 counts, viral loads (VL)) were used to indicate appointment attendance. Results Three hundred sixteen patients were in AALPHI, of whom 41% were male, 82% of black African ethnicity and 58% born abroad. At baseline (time of AALPHI interview) median [IQR] age was 17 [15–18] years, median CD4 was 597 [427, 791] cells/µL and 69% had VL ≤50c/mL. 10 patients were dropped due to missing data. 306 YPLPHIV contributed 3,585 person months of follow up across the 12 month study in which a clinic visit was recorded for 1,204 months (38/1204 dropped due to missing data). The remaining 1,166 months were classified into 3 groups: Group-A: on ART, VL ≤ 50c/mL—63%(734/1,166) visit months, Group-B: on ART, VL > 50c/mL—27%(320/1,166) Group-C: not on ART-10%(112/1,166). Most patients were engaged in care with 87% (3,126/3,585) of months fulfilling the definition of engaged in care. Conclusions The adapted algorithm allowed the varying clinical scenarios of YPLPHIV to be taken into account when measuring EIC. However availability of good quality surveillance data is crucial to ensure that EIC can be measured well.

Backgrounds and aims Pregnant women and children are not included in Egypt’s hepatitis C virus (HCV) elimination programmes. This study assesses the cost-effectiveness of several screening and treatment strategies for pregnant women and infants in Egypt.Design A Markov model was developed to simulate the cascade of care and HCV disease progression among pregnant women and their infants according to different screening and treatment strategies, which included: targeted versus universal antenatal screening; treatment of women in pregnancy or deferred till after breast feeding; treatment of infected children at 3 years vs 12 years. Current practice is targeted antenatal screening with deferred treatment for the mother and child. We also explored prophylactic treatment after birth for children of diagnosed HCV-infected women. Discounted lifetime cost, life expectancy (LE) and disability-adjusted life-years (DALYs) were calculated separately for women and their infants, and then combined.Results Current practice led to the highest cost (US$314.0), the lowest LE (46.3348 years) and the highest DALYs (0.0512 years) per mother–child pair. Universal screening and treatment during pregnancy followed by treatment of children at 3 years would be less expensive and more effective (cost saving) compared with current practice (US$219.3, 46.3525 and 0.0359 years). Prophylactic treatment at birth for infants born to HCV RNA-positive mothers would also be similarly cost saving, even with treatment uptake as low as 15% (US$218.6, 46.3525 and 0.0359 years). Findings were robust to reasonable changes in parameters.Conclusion Universal screening and treatment of HCV in pregnancy, with treatment of infected infants at age 3 years is cost saving compared with current practice in the Egyptian setting.

Identifying which young people living with perinatally acquired HIV (PHIV) are less likely to engage in care is crucial to allow targeted interventions to support them to attend clinic. We adapted an existing Engagement in Care (EIC) algorithm for adults with HIV in England, for use in young people. We applied it to data from young people with PHIV in the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort. The algorithm predicts the timing of the next scheduled clinic visit, within 1-6 months of current visit, based on routine clinical data. Follow-up was 12-months from AALPHI baseline interview. Each person-month was classified as engaged in care or not. Logistic regression models (allowing for clustered data) were used to explore baseline characteristics associated with being engaged in care, adjusting for a priori variables (time from interview, sex, age, ethnicity, country of birth). Potential characteristics were across 7 domains: sociodemographic; risk behaviour practices; mental health; cognition; clinic setting; HIV management and experience; and HIV clinical markers. Of 316 young people, 187(59%) were female, 271(86%) of black ethnicity and 184(58%) born abroad. At baseline, median [IQR] age was 17[15-18] years, and 202(69%) had viral load ≤50 copies/ml(c/mL). 87% of 3,585 person-months were classified as engaged in care. Characteristics independently associated with poorer odds of being engaged in care were: Asian/mixed/other ethnicity, vs. black ethnicity (OR 0.44, 95% CI 0.25, 0.78, p = 0.02); ever self-harmed, vs. not (OR 0.55, 95% CI 0.32, 0.95, p = 0.03); on antiretroviral therapy (ART) and self-assessed bad/not so good adherence (OR 0.46, 95% CI 0.25, 0.84) or not on ART (OR 0.64, 95% CI 0.64, 1.21) vs. on ART and good/excellent adherence (p = 0.04)); baseline VL>50c/mL, vs VL≤50c/mL (OR 0.47, 95% CI 0.30, 0.75, p = 0.002). These characteristics can help identify individuals requiring enhanced support to maintain service engagement.

Abstract Introduction Tenofovir alafenamide (TAF) is approved for paediatric use in fixed‐dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV. Methods We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009–March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0–19 years. Results and discussion Overall 3626 abstracts and 371 full papers were screened. Four single‐arm, innovator‐funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment‐experienced and virally suppressed children or adolescents. One trial also included treatment‐naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment‐naïve participants were virally suppressed (one trial). Among treatment‐experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug‐related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug‐related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z‐score (height‐ and age‐adjusted) from baseline to 48 weeks was −0.12 (interquartile range [IQR] −0.46, 0.17) to 0.05 (IQR not reported) for spine, and −0.09 (IQR −0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight‐for‐age z‐scores increased by 0.25 from baseline to 48 weeks. Conclusions Four single‐arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF‐containing regimens over 24–48 weeks. However, further comparative and longer‐term safety data are needed in children and adolescents, including on weight and metabolic changes.

Abstract Introduction Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0–19 years. Methods Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009–March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post‐treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted. Results and discussion In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single‐arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single‐arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second‐ or subsequent‐line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second‐ or subsequent‐line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0–50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug. Conclusions These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer‐term outcomes, such as weight and metabolic changes.

Learning and memory are important for successful education and career progression. We assess these functions in young people (YP) with perinatal HIV (PHIV) (with or without a previous AIDS-defining illness) and a comparable group of HIV-negative YP. 234 PHIV and 68 HIV-negative YP completed 9 tests; 5 National Institutes of Health (NIH) Toolbox tests (2 executive function, 1 speed of information processing, 2 memory); 2 Hopkins Verbal Learning Test Revised (HVLT-R) (learning (L), delayed recall (R)), and 2 verbal application measures. Z-scores for each test were calculated using normative data and averaged by domain where appropriate. The effect of predictors on test scores in the three domains with the lowest z-scores were analysed using linear regression. 139(59%) and 48(71%) PHIV and HIV-negative YP were female, 202(86%) and 52(76%) Black, and median age was 19 [17, 21] and 18 [16, 21] years respectively. 55(24%) PHIV had a previous Center for Disease Control and Prevention (CDC) class C AIDS-defining diagnosis (PHIV/C). For HVLT-R, there was a trend towards PHIV/C YP having the lowest mean z-scores (L -1.5 (95% CI -1.8,-1.2), R -1.7 (-2.0,-1.4)) followed by PHIV without a CDC C diagnosis (L -1.3 (-1.4,-1.1), R -1.4 (-1.5,-1.2)) and then the HIV-negative group (L -1.0 (-1.3,-0.7), R -1.1 (-1.3,-0.8)); all were greater than 1 SD below the reference mean. The same trend was seen for verbal application measures; however, z-scores were within 1 SD below the reference mean. NIH Toolbox tests were similar for all groups. In multivariable analyses PHIV/C and Black ethnicity predicted lower HVLT-R scores. Black ethnicity also predicted lower executive function scores, however each year increase in age predicted higher scores. In conclusion, cognitive performance in verbal learning and recall fell below population normative scores, and was more pronounced in PHIV/C, supporting wider findings that earlier antiretroviral therapy initiation, before the occurrence of AIDS-defining conditions, may protect aspects of cognitive development.