Search

Introduction: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches., Methods: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations., Results: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD., Conclusions: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The innovative Pratt pouch could optimize dispensing nevirapine prophylaxis to HIV-exposed infants in pre-measured single dose pouches to increase completion of the full 6 week infant nevirapine regimen., Materials and Methods: Nineteen health facilities with highest HIV positivity rates among pregnant women across 9 districts in southwest and central Uganda were assigned to control and intervention groups. HIV-positive women enrolled at intervention facilities received pouches filled with premeasured single doses of nevirapine using Uganda national guidelines, which were integrated into the existing drug distribution system. During antenatal care (ANC) women received 14 pouches to cover time until the 6 day postpartum visit, with an additional 8 pouches if women were delayed in returning to the facility, and 28 pouches after delivery. Women enrolled at control facilities received standard nevirapine syrup following delivery for postnatal infant prophylaxis. In a select number of intervention facilities, during ANC, women received all 42 pouches needed to complete the 6 weeks regimen. Medical record data from enrolled women were extracted; interviews with HIV-positive women during postnatal care visits were conducted. Data were collected January to August 2018 (control sites) and October 2019 to February 2020 (intervention sites). Unadjusted and adjusted logistic regression models were used to identify factors associated with facility delivery, postnatal care follow-up visit, and completion of the full 6 weeks infant nevirapine regimen., Results: Significantly more women in the intervention (n = 320) versus control (n = 340) group had facility delivery (292/316, 92.4% versus 169/340, 49.7%, p<0.0001), postnatal visits within 2 weeks postpartum (295/297, 99.3% versus 133/340, 39.1%, p<0.0001) and reported their infants completing the full 6 weeks infant prophylaxis regimen (299/313, 95.5% versus 210/242, 86.8%, p = 0.0002). Dispensing 42 versus 14 pouches during ANC did not have negative effects on these outcomes. Among out-of-facility deliveries, a higher proportion of infants received nevirapine within 72 hours of birth in the intervention versus control group, 95.8% versus 77.9%. In multivariate models, the intervention group was the only significant factor associated with facility delivery or completion of the full 6 weeks infant prophylaxis., Conclusions: Use of the Pratt pouch resulted in an increase in HIV-exposed infants completing the full 6weeks prophylaxis regimen and associated benefits including increasing facility delivery and women's adherence to postnatal care services., Competing Interests: The authors have declared that no competing interests exist.

Introduction: We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART., Methods: Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models., Results: The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P < 0.001). Using reference age group < 30 years, among conventional failures, the adjusted odds ratio (aOR) of pragmatic failure for age group 30-39 years were 0.12, 95% CI 0.03-0.57, P = 0.02 and for age group > 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06)., Conclusion: A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended., Competing Interests: The authors declare no competing interest.

Introduction: We investigated the prevalence, predictors of and effect of Antiretroviral Therapy (ART) regimen on cardiometabolic risk among HIV-positive Ugandan adults at enrolment into a prospective cohort to study the Complications of Long-Term ART (CoLTART)., Methods: We collected data on cardiometabolic risk factors including dyslipidemia, hypertension, hyperglycemia, obesity and calculated the mean atherogenic index for Plasma (AIP) and 10 year Framingham risk score (FHS). Exposures were: ART regimen, duration on ART, demographic, socio-economic, behavioral, and life-style factors including smoking, physical activity and diet (including fruit and vegetables consumption)., Results: We enrolled 1024 participants, 65% female, mean age was 44.8 years (SD 8.0) and median duration on ART was 9.4 years (IQR 6.1-9.8). The prevalence of abdominal obesity was 52.6%, BMI≥25 kg/m 2 -26.1%, hypertension-22.6%, high AIP-31.3% and FHS above 10% was 16.6%. The prevalence of low High Density Lipoprotein (HDL) was 37.5%, high Total cholesterol (Tc)-30.2%, high Low Density Lipoprotein (LDL) -23.6%, high Triglycerides (TG)-21.2%, low physical activity-46.4% and alcohol consumption-26.4%. In multivariate linear regression analyses, increasing age was associated with higher mean Tc, HDL, LDL, FHS (P<0.001) and hyperglycemia (p<0.005). In multivariate logistic regression analyses, Protease Inhibitor (PI) containing regimens were significantly associated with higher risks of abnormal: Tc, LDL, TG, AIP, abdominal obesity, hypertension, low HDL and lower risk of a FHS >10% compared to the non PI regimen., Conclusion: ART increases cardiometabolic risk. Integration of routine assessment for cardiometabolic risk factors and preventive interventions into HIV care programs in resource-limited settings is recommended.

Background: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results., Methods: HIV-positive ART naïve and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies., Results: Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001., Conclusions: Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.

Background: HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes., Findings: Between July 2013 and August 2014, 953 individuals were enrolled, 119 (12.5%) had HIV-RNA ≥1000 copies/ml and 110 were successfully genotyped; 74 (67.3%) were on first-line and 36 (32.7%) on second-line ART regimens. The predominant HIV-1 subtypes were D (34.5%), A (33.6%) and Recombinant forms (21.8%). The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested., Conclusions: In resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load monitoring, targeted HIV drug resistance testing and availability of third-line ART regimens.

Background: WHO recommends using Tenofovir containing first line antiretroviral therapy (ART), however, Tenofovir has been reported to be associated with renal impairment and dysfunction. We compared renal function among individuals on Tenofovir and those on non-Tenofovir containing ART., Methods: In a cross-sectional study of HIV-Positive adults on ART, at enrolment into a prospective cohort to study the long-term complications of ART in Uganda, information on biophysical measurements, medical history, clinical examination and renal function tests (RFTs) was collected. Fractional Tubular phosphate reabsorption and estimated glomerular filtration rate (eGFR) were calculated. Mean values of RFTs and proportions with abnormal RFTs were compared between non-Tenofovir containing (Non-TDF) and Tenofovir containing (TDF-ART) ART regimen groups using a general linear regression model. Durations of TDF exposure were also compared., Results: Between July 2013 and October 2014, we enrolled 953 individuals on ART for 6 or more months, median duration on ART was 9.3 years, 385 (40.4 %) were on non-TDF and 568 (59.6 %) on TDF-ART regimens. The proportion of participants with Proteinuria (>30 mg/dl) was higher among the TDF-ART group than the non-TDF ART group. However, in multivariable analysis, there were no significant differences in the adjusted mean differences of eGFR, serum urea, serum creatinine, fractional tubular reabsorption of phosphate and serum phosphates when patients on TDF-ART were compared with those on non-TDF containing ART. There were no differences in renal function even when different durations on Tenofovir were compared., Conclusions: We found no differences in renal function among patients on Tenofovir and non-Tenofovir containing ART for almost a decade. Tenofovir based first line ART can therefore safely be initiated even in settings without routine renal function monitoring.

Background: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm(3)., Objective: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) with mortality in the general Ugandan population and to investigate risk factors for death., Design: Population-based prospective HIV cohort., Methods: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs)., Results: A total of 374 participants with CD4 ≥350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm(3) than during periods of CD4 ≥500 cells/mm(3) although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20)., Conclusion: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.

Objective: To compare socio-demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa., Methods: Data on voluntary counselling and testing and ART use among HIV-infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio-demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2 years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates., Results: Among adults known to be HIV-infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV-diagnosed persons who were screened for ART eligibility within 2 years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites., Conclusions: Higher HIV testing rates among HIV-infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need., (© 2012 Blackwell Publishing Ltd.)

Objectives: To investigate antiretroviral therapy (ART) uptake after its introduction in 2004 in a longitudinal population-based cohort and its nested clinical cohort in rural Uganda., Methods: A HIV serosurvey of all adults aged ≥ 15 years is conducted annually. Two intervals were selected for analysis. Interval 1 (November 2004-October 2006) provided 2 years of follow-up to prospectively evaluate access to HIV services. Interval 2 (November 2007-October 2008) was used to evaluate current coverage of services. Logistic regression was used to identify sociodemographic factors associated with ART screening within 2 years of diagnosis. ART coverage was assessed using Weibull survival models to estimate the numbers needing ART., Results: In Interval 1, 636 HIV-positive adults were resident and 295 (46.4%) knew their status. Of those, 248 (84.1%) were screened for ART within 2 years of diagnosis. After adjusting for age, those who were widowed, separated or never married were more likely to be screened than those who were married. In Interval 2, 575 HIV-positive adults were residents, 322 (56.0%) knew their status, 255 (44.3%) had been screened for ART and 189 (32.9%) had started ART. Estimated ART coverage was 66%., Conclusions: In this cohort, ART access and uptake is very high once people are diagnosed. Owing to intensive screening in the study clinic, nearly all participants who were eligible initiated ART. However, this is unlikely to reflect coverage in the general population, intensified efforts are needed to promote HIV testing, and ART screening and uptake are needed among those found to be HIV-positive., (© 2012 Blackwell Publishing Ltd.)