Background The End TB Strategy aims to reduce new tuberculosis (TB) cases by 90% and TB-related deaths by 95% between 2015 – 2035. We determined the trend of case notification rates (CNRs) and treatment outcomes of TB cases with and without HIV co-infection in rural Uganda to provide an interim evaluation of progress towards this global target in rural settings. Methods We extracted retrospective programmatic data on notified TB cases and treatment outcomes from 2015 – 2019 for eight districts in rural Uganda from the District Health Information System 2. We estimated CNRs as the number of TB cases per 100,000 population. Treatment success rate (TSR) was calculated as the sum of TB cure and treatment completion for each year. Trends were estimated using the Mann–Kendall test. Results A total of 11,804 TB cases, of which 5,811 (49.2%) were HIV co-infected, were notified. The overall TB CNR increased by 3.7-fold from 37.7 to 141.3 cases per 100,000 population in 2015 and 2019 respectively. The increment was observed among people with HIV (from 204.7 to 730.2 per 100,000, p = 0.028) and HIV-uninfected individuals (from 19.9 to 78.7 per 100,000, p = 0.028). There was a decline in the TSR among HIV-negative TB cases from 82.1% in 2015 to 63.9% in 2019 (p = 0.086). Conversely, there was an increase in the TSR among HIV co-infected TB cases (from 69.9% to 81.9%, p = 0.807). Conclusion The CNR increased among people with and without HIV while the TSR reduced among HIV-negative TB cases. There is need to refocus programs to address barriers to treatment success among HIV-negative TB cases.

Background World Health Organisation recommends screening for the cryptococcal antigen (CrAg), a predictor of cryptococcal meningitis, among antiretroviral therapy (ART) naïve people living with HIV (PLHIV) with CD4 <100 cells/mm 3. CrAg positivity among ART-experienced PLHIV with viral load (VL) non-suppression is not well established, yet high VLs are associated with cryptococcal meningitis independent of CD4 count. We compared the frequency and positivity yield of CrAg screening among ART-experienced PLHIV with VL non-suppression and ART-naïve PLHIV with CD4 <100 cells/mm 3 attending rural public health facilities in Uganda. Methods We reviewed routinely generated programmatic reports on cryptococcal disease screening from 104 health facilities in eight rural districts of Uganda from January 2018 to July 2019. A lateral flow assay (IMMY CrAg®) was used to screen for cryptococcal disease. PLHIV were eligible for CrAg screening if they were ART-naïve with CD4 <100 cell/mm 3 or ART-experienced with an HIV VL >1,000 copies/ml after at least 6 months of ART. We used Pearson’s chi-square test to compare the frequency and yield of CrAg screening. Results Of 71,860 ART-experienced PLHIV, 7210 (10.0%) were eligible for CrAg screening. Among 15,417 ART-naïve PLHIV, 5,719 (37.1%) had a CD4 count measurement, of whom 937 (16.4%) were eligible for CrAg screening. The frequency of CrAg screening was 11.5% (830/7,210) among eligible ART-experienced PLHIV compared to 95.1% (891/937) of eligible ART- naïve PLHIV (p<0.001). The CrAg positivity yield was 10.5% among eligible ART-experienced PLHIV compared to 13.8% ART-naïve PLHIV (p=0.035). Conclusion The low frequency and high positivity yield of CrAg screening among ART-experienced PLHIV with VL non-suppression suggest a need for VL- directed CrAg screening in this population. Studies are needed to evaluate the cost-effectiveness and impact of CrAg screening and fluconazole prophylaxis on the outcomes of ART – experienced PLHIV with VL non-suppression.

Provision of Isoniazid Preventive Therapy (IPT) as part of the comprehensive TB/HIV prevention intervention for people living with HIV & AIDS was recommended by WHO in 2011. Literature shows that Isoniazid (INH) associated hepatotoxicity is a common drug adverse event among people taking INH, and that it's associated with a high risk of mortality. These case series document INH associated hepatotoxicity in HIV-infected children receiving IPT in a resource constrained setting. They also further describe the challenges and lessons learnt while providing routine IPT among HIV-infected children in a resource-limited setting where laboratory tests for liver function monitoring are not performed routinely. The case series describe observed cases which presented to the Mildmay Uganda HIV/AIDS clinic between December 2013 and March 2014. The findings demonstrate that: 1) there was a 1.5% INH related hepatotoxicity incidence among children of four to ten years old; 2) 20% death rate-one out of the five children died and; 3) hepatotoxicity events on average occurred at 10.8 weeks after INH initiation while at the same time, all the cases had liver enzymes elevated above 10 times the upper normal limit values and reported late for medical intervention. The insidious onset of symptoms and signs of INH related hepatotoxicity coupled with lack of adequate resources needed to manage the condition were the major challenges to provision of routine IPT among children living with HIV in resource-limited settings in sub-Sahara Africa. Clinical vigilance, continuous education of clients and caretakers about the * Corresponding author. L. Nsobya et al. 385 side effects or adverse events of INH and routine laboratory examination of liver function tests during follow-up of IPT in HIV-infected children are recommended to enhance early detection and prompt management of IPT associated hepatotoxicity.