Impact of a mobile phone-based interactive voice response software on tuberculosis treatment outcomes in Uganda (CFL-TB): a protocol for a randomized controlled trial.

BACKGROUND: Throughout the last decade, tuberculosis (TB) treatment success has not surpassed 90%, the global target. The impact of mobile health interventions (MHIs) on TB treatment outcomes is unknown, especially in low- and middle-income countries (LMICs). MHIs, including interactive voice response technology (IVRT), may enhance adherence and retention in the care of patients with tuberculosis and improve TB treatment outcomes. This study seeks to determine the impact of IVRT-based MHI on TB treatment success (treatment completion and cure rates) in patients with TB receiving care at five public health facilities in Uganda. METHODS: We used a theory-based and human-centered design (HCD) to adapt an already piloted software to design "Call for life-TB" (CFL-TB), an MHI that utilizes IVRT to deliver adherence and appointment reminders and allows remote symptom reporting. This open-label, multicenter, randomized controlled trial (RCT), with nested qualitative and economic evaluation studies, will determine the impact of CFL-TB on TB treatment success in patients with drug-susceptible TB in Uganda. Participants (n = 274) at the five study sites will be randomized (1:1 ratio) to either control (standard of care) or intervention (adherence and appointment reminders, and health tips) arms. Multivariable regression models will be used to compare treatment success, adherence to treatment and clinic appointments, and treatment completion at 6 months post-enrolment. Additionally, we will determine the cost-effectiveness, acceptability, and perceptions of stakeholders. The study received national ethical approval and was conducted in accordance with the international ethical guidelines. DISCUSSION: This randomized controlled trial aims to evaluate interactive voice response technology in the context of resource-limited settings with a high burden of TB and high illiteracy rates. The software to be evaluated was developed using HCD and the intervention was based on the IMB model. The software is tailored to the local context and is interoperable with the MHI ecosystem. The HCD approach ensures higher usability of the MHI by integrating human factors in the prototype development. This research will contribute towards the understanding of the implementation and impact of the MHI on TB treatment outcomes and the health system, especially in LMICs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04709159 . Registered on January 14, 2021.

The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women.

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir. METHODS: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. RESULTS: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. CONCLUSIONS: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.

Predicting the Impact of COVID-19 and the Potential Impact of the Public Health Response on Disease Burden in Uganda.

The COVID-19 pandemic and public health "lockdown" responses in sub-Saharan Africa, including Uganda, are now widely reported. Although the impact of COVID-19 on African populations has been relatively light, it is feared that redirecting focus and prioritization of health systems to fight COVID-19 may have an impact on access to non-COVID-19 diseases. We applied age-based COVID-19 mortality data from China to the population structures of Uganda and non-African countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. We then predicted the impact of possible scenarios of the COVID-19 public health response on morbidity and mortality for HIV/AIDS, malaria, and maternal health in Uganda. Based on population age structure alone, Uganda is predicted to have a relatively low COVID-19 burden compared with an equivalent transmission in comparison countries, with 12% of the mortality and 19% of the lost DALYs predicted for an equivalent transmission in Italy. By contrast, scenarios of the impact of the public health response on malaria and HIV/AIDS predict additional disease burdens outweighing that predicted from extensive SARS-CoV-2 transmission. Emerging disease data from Uganda suggest that such deterioration may already be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non-COVID-19 disease burden from a prolonged lockdown response. This may reverse hard-won gains in addressing fundamental vulnerabilities in women and children's health, and underlines the importance of tailoring COVID-19 responses according to population structure and local disease vulnerabilities.

Relationship between socioeconomic status and risk of sexually transmitted infections in Uganda: Multilevel analysis of a nationally representative survey.

Socioeconomic status (SES) appears to have positive and negative associations with sexually transmitted infection (STI) risk in resource-limited settings, but few studies have evaluated nationally representative data. We assessed multiple SES measures and their effect on STI risk. We conducted a secondary analysis of data from the Uganda Demographic and Health Survey (UDHS 2011). The primary outcome (STI risk) was self-reported STIs and/or symptoms in the prior 12 months. We examined associations between multiple SES measures and STI risk using a mixed-effects Poisson regression model. The results showed that of the 9256 sexually active individuals, 7428 women and 1828 men were included in the analysis. At an individual level, middle wealth quintile and disposable income were associated with STI risk, whereas being in the richest wealth quintile was protective. Residence in wealthier regions (adjusted incidence rate ratio [aIRR] 3.92, 3.62, and 2.75, for Central, Western, and Eastern regions; p < 0.01) was associated with increased STI risk. Regional level analysis revealed stochastic variability of STI risk across geographical region (variance 0.03; p = 0.01). The bilateral association between SES and STI risk underscores the need for multi-sectoral interventions to address the upstream effects of poverty on STI risk and downstream effects of STIs on health and economic productivity.

Assessment of parasite clearance following treatment of severe malaria with intravenous artesunate in Ugandan children enrolled in a randomized controlled clinical trial.

BACKGROUND: Malaria control largely depends on availability of highly efficacious drugs, however, over the years, has been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti-malarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intravenous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti-malarial effectiveness. METHODS: Parasite clearance data obtained from a clinical trial whose objective was to evaluate the 42-day parasitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus artemisinin-based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6-hourly blood smears post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study endpoints were; parasite clearance half-life (the time required for parasitaemia to decrease by 50% based on the linear portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial parasitaemia). RESULTS: One hundred and fifty participants with severe malaria were enrolled. All participants were treated with intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to complete parasite clearance was of 2 (1-2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61-7.10) and 17.55 (14.66-20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median (IQR) slope half-life was 2.15 (1.64, 2.61) h. CONCLUSION: Parasite clearance following treatment with intravenous artesunate was rapid and adequate. This finding provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Continuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmission areas in sub-Saharan Africa where spread of resistance would be disastrous. Trial registration The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011, http://www.pactr.org/ ).

Innovative Demand Creation for Voluntary Medical Male Circumcision Targeting a High Impact Male Population: A Pilot Study Engaging Pregnant Women at Antenatal Clinics in Kampala, Uganda.

BACKGROUND: Circumcision has been shown to be an effective method of HIV prevention; however, only 27% of Ugandan men aged 15-49 years are circumcised. There is a paucity of data on the role of intimate partners in generating demand for voluntary medical male circumcision (VMMC). We conducted a pilot study to assess the feasibility of a partner-focused intervention targeting males >25 years. METHODS: Among pregnant women in their third trimester attending antenatal care we evaluated the impact of a pilot behavior change intervention on VMMC through a quasi-experimental approach. We observed VMMC numbers among spouses of women as per standard practice (comparison phase), and after introducing a behavioral change communication package (intervention phase). Logistic regression was used to compare the odds of VMMC uptake between comparison and intervention phases. We used qualitative methods to evaluate the casual chain using a thematic approach. RESULTS: Of the 601 women studied, 90% articulated the health benefits of VMMC and 99% expressed interest in their spouse getting circumcised. Women's knowledge was not increased by the intervention. Four men were circumcised in the comparison and 7 in the intervention phase. The intervention was not associated with higher odds of circumcision (odds ratio 1.5, 95% CI: 0.3 to 6.0, P = 0.65). We interviewed 117 individuals overall with the main enablers for VMMC being: free VMMC, transport reimbursement, and health benefits. Deterrents included misconceptions, lost wages and fear of pain. Most of the uncircumcised men interviewed reported interest in VMMC. CONCLUSIONS: Our pilot intervention had no significant impact on increasing VMMC demand. The study demonstrated the feasibility of pregnant women engaging their spouses to discuss VMMC.

Implementation and Operational Research: Impact of Nurse-Targeted Care on HIV Outcomes Among Immunocompromised Persons: A Before-After Study in Uganda.

INTRODUCTION: Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic-based nurse care on antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons. METHODS: The study included ART-naive patients with CD4 counts <100 cells per microliter registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost to follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention. RESULTS: The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (P < 0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (P = 0.001). A 21% increase in the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed. CONCLUSIONS: Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention.

Is CD4 monitoring needed among ugandan clients achieving a virologic and immunologic response to treatment?

It is unclear whether ongoing CD4 monitoring is needed following immunologic and virologic response to antiretroviral therapy (ART). We investigated the proportion of clients who achieved a virologic and immunologic response and then had a subsequent CD4 count <200 cells/µL despite continued virologic suppression. Included in this analysis were clients receiving ART through the Rakai Health Sciences Program between June 2004-May 2013 who achieved a CD4 ≥200 cells/µL and VL ≤400 copies/mL and who had three sets of CD4 and VL measurements (defined as a sequence) within a 390 day period. A CD4 decline was defined as any drop in CD4 count to <200 cells/µL during a period of viral suppression. A total of 1553 clients were included, 68% females, mean age of 35.5 years (SD 8.3), median baseline CD4 count 183 cells/µL (IQR 106-224). 43 (2.8%) clients developed CD4 declines, the majority, 32/43 (74%), among individuals whose initial CD4 was <300 cells/µL. Of the 43 clients with CD4 declines, 24 had an additional CD4 measurement and 20/24 (83%) achieved a CD4 ≥200 cell/µL on their next measurement (median 285 cells/µL; IQR 220-365). CD4 declines were significantly greater among those with lower CD4 at sequence initiation [adjusted hazard ratio (AHR) 4.3 (95% CI 2.1, 9.0) CD4 200-249 versus ≥350 cells/µL]. Clients who achieved an immunologic and virologic response to ART were unlikely to experience a subsequent CD4 count decline to <200 cells/µL, and among those experiencing a decline, the majority were transient in nature. Thus, ongoing CD4 monitoring could be omitted.

Cost effectiveness of a pharmacy-only refill program in a large urban HIV/AIDS clinic in Uganda.

BACKGROUND: HIV/AIDS clinics in Uganda and other low-income countries face increasing numbers of patients and workforce shortages. We performed a cost-effectiveness analysis comparing a Pharmacy-only Refill Program (PRP), a form of task-shifting, to the Standard of Care (SOC) at a large HIV/AIDS clinic in Uganda, the Infectious Diseases Institute (IDI). The PRP was started to reduce workforce shortages and optimize patient care by substituting pharmacy visits for SOC involving monthly physician visits for accessing antiretroviral medicines. METHODOLOGY/PRINCIPAL FINDINGS: We used a retrospective cohort analysis to compare the effectiveness of the PRP compared to SOC. Effectiveness was defined as Favorable Immune Response (FIR), measured as having a CD4 lymphocyte count of over 500 cells/µl at follow-up. We used multivariate logistic regression to assess the difference in FIR between patients in the PRP and SOC. We incorporated estimates of effectiveness into an incremental cost-effectiveness analysis performed from a limited societal perspective. We estimated costs from previous studies at IDI and conducted univariate and probabilistic sensitivity analyses. We identified 829 patients, 578 in the PRP and 251 in SOC. After 12.8 months (PRP) and 15.1 months (SOC) of follow-up, 18.9% of patients had a FIR, 18.6% in the PRP and 19.6% in SOC. There was a non-significant 9% decrease in the odds of having a FIR for PRP compared to SOC after adjusting for other variables (OR 0.93, 95% CI 0.55-1.58). The PRP was less costly than the SOC (US$ 520 vs. 655 annually, respectively). The incremental cost-effectiveness ratio comparing PRP to SOC was US$ 13,500 per FIR. PRP remained cost-effective at univariate and probabilistic sensitivity analysis. CONCLUSION/SIGNIFICANCE: The PRP is more cost-effective than the standard of care. Similar task-shifting programs might help large HIV/AIDS clinics in Uganda and other low-income countries to cope with increasing numbers of patients seeking care.