Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda.

Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range: 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients' baseline characteristics (adjusted prevalence ratio [aPR] = 2.58 [95%CI 2.45, 2.72], P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was: 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients' baseline characteristics (aPR [95%CI] = 1.09 [1.04, 1.14], P value<0.001, and 1.10 [1.05,1.15], P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains.

Adherence of health workers to guidelines for screening and management of cryptococcal meningitis in Uganda.

INTRODUCTION: Health workers' failure to adhere to guidelines for screening, diagnosis and management of HIV-associated cryptococcal meningitis (CM) remains a significant public health concern. We aimed to assess adherence to the standards of care and management of HIV patients at risk of CM per the MoH guidelines and assess stock management of CM supplies in the period of January to June 2021 at selected public health facilities (HFs) in Uganda. METHODS: The study employed an observational cross-sectional design to assess the level of adherence of health workers to standards of clinical care and management of HIV positive patients at risk of CM as per the clinical guidelines for Uganda, and stock management of CM supplies in the period of January to June 2021in selected public health facilities. The study team used a survey guide designed by MoH to assess and score the screening, diagnosis and management practices of Health Facilities towards CM. Scoring was categorized as red (< 80%), light green (80%-95%), and dark green (˃95%) in the order from worst to best adherence. The data was transcribed into a spread sheet and analysed using STATA-v15. RESULTS: The study team visited a total of 15 public health facilities including 5 general hospitals, 9 regional referral hospitals (RRHs) and 1 National Referral hospital (NRH). The mean score for adherence to screening and management of CM for all the combined facilities was 15 (64.7%) classified as red. 10 (66.7%) HFs had not performed a baseline CD4 test for eligible patients within 2 weeks of ART initiation. With regards to treatment, 9 (60%) of the HFs were scored as light green on knowledge of the procedure for reconstituting intravenous Liposomal Amphotericin B. None of the HFs visited had potassium chloride tablets in stock. CONCLUSION: Major MoH guidelines are generally not being adhered to by health workers while managing cryptococcal meningitis. It is vital that government and implementing partners regularly support HFs with training, mentorship, and support supervision on CM management to improve adherence to CM screening and treatment guidelines.

Characterizing plasma albumin concentration changes in TB/HIV patients on anti retroviral and anti -tuberculosis therapy.

PURPOSE: Plasma albumin, a biomarker for hepatic function, is reported to correspondingly decrease in concentration as disease severity increases in chronic infections including HIV and TB. Our objective was to develop a semi-mechanistic disease progression model to quantify plasma albumin concentration changes during TB and HIV therapy and identify the associated covariate factors. METHODS: Plasma albumin concentration data was collected at specified times for 3 months from 262 HIV participants receiving efavirenz based anti retroviral therapy. Of these, 158 were TB co-infected and on Rifampicin based anti -tuberculosis co-treatment. An indirect response model with zero order albumin production and first order elimination was developed in NONMEM version 7.2 to describe our data. Genotype (CYP2B6*6 and 11, CYP3A5, ABCB1c.3435C>T and ABCB1rs), TB disease status, baseline age, body weight, plasma creatinine, alanine transaminase enzyme and CD4(+) count were the potential model covariates tested. RESULTS: The proposed model successfully described plasma albumin concentration changes in the study population. There was a 10.9% and 48.6% increase in albumin production rates in HIV only and TB co-infected participants respectively. Participants co-infected with TB showed a 44.2% lower baseline albumin secretion rate than those without TB while ABCB1c.3435C>T mutation was associated with a 16% higher steady state albumin secretion rate following treatment. CONCLUSION: A semi-mechanistic model describes plasma albumin concentration changes in HIV patients on ART. Further work is required to establish the utility of the model in monitoring disease progression and predicting prognosis in HIV and TB co-infected patients in absence of or during treatment.

Over-the-counter suboptimal dispensing of antibiotics in Uganda.

BACKGROUND: Overuse and misuse of antibiotics is a serious global problem. While resistance to older antibiotics is increasing, development of newer molecules has stalled. Resistance to the existing antibiotics that is largely driven by their high-volume use is a global public health problem. Uganda is one of the countries where prescription-only drugs, including antibiotics, can be obtained over the counter. We determined the rate of antibiotic dispensing and use in Uganda. METHODS: The study utilized a descriptive cross-sectional study design to determine the number of antibiotic "prescribed" daily doses per 1,000 clients. Data were collected from one health center II, eight general/district hospitals, one national referral hospital, and 62 registered community pharmacies. From each study site, data were collected for five consecutive days over the months of November 2011 to January 2012. RESULTS: The overall antibiotic issue rate was 43.2%. Amoxicillin, metronidazole, ciprofloxacin, sulfamethoxazole-trimethoprim, cloxacillin, and ampicillin, belonging to the WHO anatomical therapeutic chemical classifications of penicillin with extended spectra, imidazole derivatives, fluoroquinolones, and sulfonamide-trimethoprim combinations, constituted 70% of the issued antibiotics. About 41% of antibiotics were issued over the counter. At community pharmacies, where 30% of antibiotic dispensing occurred, the number of prescribed daily doses/1,000 antibiotic clients was 4,169 compared to 6,220, 7,350 and 7,500 at general/district hospitals, the national referral hospital, and the health center, respectively. CONCLUSION: In Uganda, at least four in every ten individuals that visit a health-care facility are treated with an antibiotic. Antibiotics are largely given as over-the-counter drugs at community pharmacies. The number of antibiotic prescribed daily doses/1,000 antibiotic clients does not significantly differ between categories of health-care facilities except at community pharmacies, where lower doses are dispensed compared to other health-care facilities.