Insulin resistance and intestinal integrity in children with and without HIV infection in Uganda.

OBJECTIVES: The risk of cardiometabolic complications in children with perinatally acquired HIV infection (PHIVs) and in perinatally HIV-exposed but uninfected children (HEUs) and its relationship to systemic inflammation and markers of gut integrity are not well established. In this current study, we assed insulin resitance in PHIV compared to HEUs and HIV unexposed uninfected children and explored potential association with intestinal damage biomarkers. METHODS: This was a cross-sectional study in PHIVs, HEUs and HIV-unexposed, uninfected children (HUUs) aged 2-10 years enrolled in Uganda. PHIVs were on stable antiretroviral therapy (ART) with HIV viral load  < 400 HIV-1 RNA copies/mL. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). We measured markers of systemic inflammation, monocyte activation and gut integrity. Kruskal-Wallis tests were used to compare markers by HIV status; Pearson correlation and multiple linear regressions were used to assess associations of the HOMA-IR index with biomarkers of intestinal damage and translocation. RESULTS: Overall, 172 participants were enrolled in the study (57 PHIVs, 59 HEUs and 56 HUUs). The median age was 7.8 [interquartile range (IQR) 6.39, 8.84] years, 55% were female and the median body mass index (BMI) was 15 (IQR 14.3, 15.8) kg/m2 . Among PHIVs, the median CD4% was 37%, and 93% had viral load ≤ 20 copies/mL. PHIVs had higher waist:hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides and HOMA-IR index than the other groups (P ≤ 0.02). Factors correlated with insulin resistance included higher BMI and HDL cholesterol and lower soluble tumour necrosis factor receptor I (sTNFRI) (P ≤ 0.02). There was no correlation between any of the other inflammatory or gut biomarkers and HOMA-IR index (P ≥ 0.05). After adjusting for age and sTNFRI, BMI remained independently associated with the HOMA-IR index (ß = 0.16; P < 0.01). CONCLUSIONS: Despite viral suppression, Ugandan PHIVs have disturbances in glucose metabolism. Higher BMI, and not immune activation or alteration of gut integrity, was associated with insulin resistance in this population.

Beyond clinical trials: Cross-sectional associations of combination antiretroviral therapy with reports of multiple symptoms and non-adherence among adolescents in South Africa.

BACKGROUND: Studies investigating symptoms associated with combination antiretroviral therapy (cART) use among adolescents in resource-limited settings are rare beyond clinical trials. Identifying adolescents at risk of non-adherence is imperative for HIV/AIDS programming and controlling the epidemic in this key population. OBJECTIVE: To examine which cART regimens were associated with reports of multiple symptoms and past-week non-adherence in a large community-traced sample of HIV-positive adolescents in South Africa (SA). METHODS: A total of 1 175 HIV-positive ART-experienced adolescents aged 10 - 19 years attending 53 health facilities in the Eastern Cape Province, SA, were interviewed in 2014 - 2015. Ninety percent (n=1 059) were included in the study. Adolescents who reported no medication use and those with unclear or missing data were excluded from further analysis, resulting in a sample for analysis of n=501. Outcomes were reports of multiple symptoms (three or more symptoms in the past 6 months) and past-week ART non-adherence (<95% correct doses in the past week). Multivariable logistic regression analyses controlled for sociodemographic and HIV-related covariates in Stata 13/IC. RESULTS: Of the adolescents included, 54.3% were female. The median age was 14 (interquartile range 12 - 16) years, and 66.5% were vertically infected. The prevalence of multiple symptoms was 59.7% (95% confidence interval (CI) 55.3 - 63.9). Independent of covariates, stavudine (d4T)-containing cART regimens and the fixed-dose combination of tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) were associated with more reports of multiple symptoms (adjusted odds ratio (aOR) 3.38; 95% CI 1.19 - 9.60 and aOR 2.67; 95% CI 1.21 - 5.88, respectively). Lopinavir/ritonavir (LPV/r)-containing regimens were associated with fewer reports of multiple symptoms (aOR 0.47; 95% CI 0.21 - 1.04). For EFV-based regimens, adolescents on d4T + lamivudine (3TC) + EFV were more likely to report multiple symptoms than those on TDF + FTC + EFV or those on abacavir (ABC) + 3TC + EFV (aOR 3.26; 95% CI 1.01 - 10.52, aOR 2.86; 95% CI 1.35 - 6.05 and aOR 1.08; 95% CI 0.64 - 1.82, respectively). However, only TDF + FTC + EFV cART was associated with lower levels of non-adherence among participants (aOR 0.44; 95% CI 0.21 - 0.93). CONCLUSIONS: Rates of multiple symptoms among HIV-positive ART-experienced adolescents were high. d4T-containing regimens and TDF + FTC + EFV were associated with more reports of multiple symptoms, whereas LPV/r-containing regimens were associated with fewer reports. However, adolescents on TDF + FTC + EFV were the most adherent subgroup. These findings support the World Health Organization-recommended discontinuation of d4T use, but also underscore the dilemma faced by clinicians when choosing between low-toxicity regimens and those that promote ART adherence, particularly among HIV-positive adolescents.

Improved Adherence to Antiretroviral Therapy Observed Among HIV-Infected Children Whose Caregivers had Positive Beliefs in Medicine in Sub-Saharan Africa.

A high level of adherence to antiretroviral treatment is essential for optimal clinical outcomes in HIV infection, but measuring adherence is difficult. We investigated whether responses to a questionnaire eliciting caregiver beliefs in medicines were associated with adherence of their child (median age 2.8 years), and whether this in turn was associated with viral suppression. We used the validated beliefs in medicine questionnaire (BMQ) to measure caregiver beliefs, and medication event monitoring system caps to measure adherence. We found significant associations between BMQ scores and adherence, and between adherence and viral suppression. Among children initiating Antiretroviral therapy (ART), we also found significant associations between BMQ 'necessity' scores, and BMQ 'necessity-concerns' scores, and later viral suppression. This suggests that the BMQ may be a valuable tool when used alongside other adherence measures, and that it remains important to keep caregivers well informed about the long-term necessity of their child's ART.

Population level usage of health services, and HIV testing and care, prior to decentralization of antiretroviral therapy in Agago District in rural Northern Uganda.

BACKGROUND: Decentralization of ART services scaled up significantly with the country wide roll out of option B plus in Uganda. Little work has been undertaken to examine population level access to HIV care particularly in hard to reach areas in rural Africa. Most work on ART scale up has been done at health facility level which omits people not accessing healthcare in the community. This study describes health service usage, particularly HIV testing and care in 2/6 parishes of Lapono sub-county of northern Uganda, prior to introduction of ART services in Lira Kato Health Centre (a local lower-level health centre III), as part of ART decentralization. METHODS: Household and individual questionnaires were administered to household members (aged 15-59 years). Logit random effects models were used to test for differences in proportions (allowing for clustering within villages). RESULTS: 2124 adults from 1351 households were interviewed (755 [36%] males, 1369 [64 %] females). 2051 (97%) participants reported seeking care locally for fever, most on foot and over half at Lira Kato Health Centre. 574 (76%) men and 1156 (84%) women reported ever-testing for HIV (P < 0.001 for difference); 34/574 (6%) men and 102/1156 (9%) women reported testing positive (P = 0.04). 818/850 (96%) women who had given birth in the last 5 years had attended antenatal care in their last pregnancy: 7 women were already diagnosed with HIV (3 on ART) and 790 (97%) reported being tested for HIV (34 tested newly positive). 124/136 (91%) HIV-positive adults were in HIV-care, 123/136 (90 %) were taking cotrimoxazole and 74/136 (54%) were on ART. Of adults in HIV-care, most were seen at Kalongo hospital (n = 87), Patongo Health Centre (n = 7) or Lira Kato Health Centre (n = 23; no ART services). 58/87, 5/7 and 20/23 individuals walked to Kalongo hospital (56 km round-trip, District Health Office information), Patongo Health Centre (76 km round-trip, District Health Office information) and Lira Kato Health Centre (local) respectively. 8 HIV-infected children were reported; only 2 were diagnosed aged <24 months: 7/8 were in HIV-care including 3 on ART. CONCLUSIONS: Higher proportions of women compared to men reported ever-testing for HIV and testing HIV-positive, similar to other surveys. HIV-infected men and women travelled considerable distances for ART services. Children appeared to be under-accessing testing and referral for treatment. Decentralization of ART services to a local health facility would decrease travel time and transport costs, making care and treatment more easily accessible.