Koen Frederix

Decentralization of pediatric HIV care and treatment in five sub-Saharan African countries.

Background:In resource-limited settings, decentralization of HIV care and treatment is a cornerstone of universal care and rapid scale-up. We compared trends in pediatric enrollment and outcomes at primary (PHFs) vs secondary/tertiary health facilities (SHFs). Methods:Using aggregate program data reported quarterly from 274 public facilities in Kenya, Lesotho, Mozambique, Rwanda, and Tanzania from January 2008 to March 2010, we examined trends in number of children younger than 15 years of age initiating antiretroviral treatment (ART) by facility type. We compared clinic-level lost to follow-up (LTFU) and mortality per 100 person-years (PYs) on ART during the period by facility type. Results:During the 2-year period, 17,155 children enrolled in HIV care and 8475 initiated ART in 182 (66%) PHFs and 92(34%) SHFs. PHFs increased from 56 to 182, whereas SHFs increased from 72 to 92 sites. SHFs accounted for 71% of children initiating ART; however, the proportion of children initiating ART each quarter at PHFs increased from 17% (129) to 44% (463) in conjunction with an increase in PHFs during observation period. The average LTFU and mortality rates for children on ART were 9.8/100 PYs and 5.2/100 PYs, respectively, at PHFs and 20.2/100 PYs and 6.0/100 PYs, respectively, at SHFs. Adjusted models show PHFs associated with lower LTFU (adjusted rate ratio = 0.55; P = 0.022) and lower mortality (adjusted rate ratio = 0.66; P = 0.028). Conclusions:The expansion of pediatric services to PHFs has resulted in increased numbers of children on ART. Early findings suggest lower rates of LTFU and mortality at PHFs. Successful scale-up will require further expansion of pediatric services within PHFs.

Using mHealth for HIV/TB Treatment Support in Lesotho: Enhancing Patient-Provider Communication in the START Study.

Background: mHealth is a promising means of supporting adherence to treatment. The Start TB patients on ART and Retain on Treatment (START) study included real-time adherence support using short-text messaging service (SMS) text messaging and trained village health workers (VHWs). We describe the use and acceptability of mHealth by patients with HIV/tuberculosis and health care providers. Methods: Patients and treatment supporters received automated, coded medication and appointment reminders at their preferred time and frequency, using their own phones, and

The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial.

3.70 in monthly airtime. Facility-based VHWs were trained to log patient information and text message preferences into a mobile application and were given a password-protected mobile phone and airtime to communicate with community-based VHWs. The use of mHealth tools was analyzed from process data over the study course. Acceptability was evaluated during monthly follow-up interviews with all participants and during qualitative interviews with a subset of 30 patients and 30 health care providers at intervention sites. Use and acceptability were contextualized by monthly adherence data. Findings: From April 2013 to August 2015, the automated SMS system successfully delivered 39,528 messages to 835 individuals, including 633 patients and 202 treatment supporters. Uptake of the SMS intervention was high, with 92.1% of 713 eligible patients choosing to receive SMS messages. Patient and provider interviews yielded insight into barriers and facilitators to mHealth utilization. The intervention improved the quality of health communication between patients, treatment supporters, and providers. HIV-related stigma and technical challenges were identified as potential barriers. Conclusions: The mHealth intervention for HIV/tuberculosis treatment support in Lesotho was found to be a low-tech, user-friendly intervention, which was acceptable to patients and health care providers.

Reaching the end of the line: Operational issues with implementing phone-based unannounced pill counts in resource-limited settings

Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa.Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa.

Prevalence, patterns, and correlates of HIV disclosure among TB-HIV patients initiating antiretroviral therapy in Lesotho

Introduction Accurate measurement of adherence is necessary to ensure that therapeutic outcomes can be attributed to the recommended treatment. Phone-based unannounced pill counts were shown to be feasible and reliable measures of adherence in developed settings; and have been further used as part of medication adherence interventions. However, it is not clear whether this method can be implemented successfully in resource-limited settings, where cellular network and mobile phone coverage may be low. Our objective is to describe operational issues surrounding the use of phone-based unannounced pill counts in Lesotho and Ethiopia. Methods Phone-based monthly unannounced pill counts, using an adaptation of a standardized protocol from previous US-based studies, were utilized to measure anti-TB and antiretroviral medication adherence in two implementation science studies in resource-limited settings, START (Lesotho) and ENRICH (Ethiopia). Results In START, 19.6% of calls were completed, with 71.9% of participants reached at least once; majority of failed call attempts were due to phones not being available (54.8%) or because participants were away from the pills (32.7%). In ENRICH, 33.5% of calls were completed, with 86.7% of participants reached at least once; the main reasons for failed call attempts were phones being switched off (31.5%), participants not answering (27.3%), participants’ discomfort speaking on the phone (15.4%), and network problems (13.2%). Structural, facility-level, participant-level, and data collection challenges were encountered in these settings. Discussion Phone-based unannounced pill counts were found to be challenging, and response rates suboptimal. While some of these challenges were specific to local contexts, most of them are generalizable to resource-limited settings. In a research study context, a possible solution to ease operational challenges may be to focus phone-based unannounced pill count efforts on a randomly selected sample from participants who are provided with study phones and rigorously ensure that call attempts are made for these participants.

Tuberculosis preventive treatment preferences among care givers of children in Lesotho: a pilot study

ABSTRACT Disclosure of HIV-positive status has important implications for patient outcomes and preventing HIV transmission, but has been understudied in TB-HIV patients. We assessed disclosure patterns and correlates of non-disclosure among adult TB-HIV patients initiating ART enrolled in the START Study, a mixed-methods cluster-randomized trial conducted in Lesotho, which evaluated a combination intervention package (CIP) versus standard of care. Interviewer-administered questionnaire data were analyzed to describe patterns of disclosure. Patient-related factors were assessed for association with non-disclosure to anyone other than a health-care provider and primary partners using generalized linear mixed models. Among 371 participants, 95% had disclosed their HIV diagnosis to someone other than a health-care provider, most commonly a spouse/primary partner (76%). Age, TB knowledge, not planning to disclose TB status, greater perceived TB stigma, and CIP were associated with non-disclosure in unadjusted models (p < .1). In adjusted models, all point estimates were similar and greater TB knowledge (adjusted odds ratio [aOR] 0.59, 95% confidence interval [CI] 0.39–0.90) and CIP (aOR 0.20, 95% CI 0.05–0.79) remained statistically significant. Among 220 participants with a primary partner, 76% had disclosed to that partner. Significant correlates of partner non-disclosure (p < .1) in unadjusted analyses included being female, married/cohabitating, electricity at home, not knowing if partner was HIV-positive, and TB knowledge. Adjusted point estimates were largely similar, and being married/cohabitating (aOR 0.03, 95% CI 0.01–0.12), having electricity at home (aOR 0.38, 95% CI 0.17–0.85) and greater TB knowledge (aOR 0.76, 95% CI 0.59–0.98) remained significant. In conclusion, although nearly all participants reported disclosing their HIV status to someone other than a health-care provider at ART initiation, nearly a quarter of participants with a primary partner had not disclosed to their partner. Additional efforts to support HIV disclosure (e.g., counseling) may be needed for TB-HIV patients, particularly for women and those unaware of their partners’ status.

Use of Index Patients to Enable Home-Based Testing in Lesotho

BACKGROUND Shorter-duration regimens for preventing drug-susceptible tuberculosis (TB) have been shown to be safe and efficacious in children, and may improve acceptability, adherence, and treatment completion. While these regimens have been used in children in low TB burden countries, they are not yet widely used in high TB burden countries. SETTING Five health facilities in one district in Lesotho, a high TB burden country. OBJECTIVE Assess the preventive treatment preferences of care givers of child TB contacts. DESIGN Qualitative data were collected using in-depth interviews with 12 care givers whose children completed preventive treatment, and analyzed using grounded theory. FINDINGS Care givers were interested in being involved in the childrens treatment decisions. Pill burden, treatment duration and related frequency of dosing were identified as important factors that influenced preventive treatment preferences among care givers. CONCLUSION Understanding care giver preferences and involving them in treatment decisions may facilitate efforts to implement successful preventive treatment for TB among children in high TB burden countries.

Pulmonary tuberculosis diagnostic practices among people living with the human immunodeficiency virus in Lesotho

cost-effectiveness analysis. PLoS Med. 2011; 8:e1001058. 21. Snyder L. American College of Physicians Ethics Manual: sixth edition. Ann Intern Med. 2012;156:73. 22. A policy paper of the American College of Physicians. How Can Our Nation Conserve and Distribute Health Care Resources Effectively and Efficiently? 2011. Available at: https://www.acponline.org/system/files/ documents/advocacy/current_policy_papers/ assets/health_care_resources.pdf. Accessed June 27, 2017. 23. Aleem IS, Schemitsch EH, Hanson BP. What is a clinical decision analysis study? Indian J Orthop. 2008;42:137–139. 24. Liu AY, et al. Preexposure prophylaxis for HIV infection integrated with municipaland community-based sexual health services. JAMA Intern Med. 2016;176:75–84. 25. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191: 654–665. 26. Koblin B, Chesney M, Coates T; EXPLORE Study Team. Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study. Lancet. 2004;364:41–50. 27. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011; 365:493–505. 28. Beer L, Bradley H, Mattson CL, et al. Trends in racial and ethnic disparities in antiretroviral therapy prescription and viral suppression in the United States, 2009–2013: trends in disparities in HIV care. J Acquir Immune Defic Syndr. 2016;73:446–453. 29. Desai M. Baseline predictors of HIV infection in the no-PrEP Group in the PROUD trial. Presented at: Annual Conference of the British HIV Association; April 19-22, 2016; Manchester. 30. Heuker J, Sonder GJB, Stolte I, et al. High HIV incidence among MSM prescribed postexposure prophylaxis, 2000-2009: indications for ongoing sexual risk behaviour. AIDS. 2012;26:505–512. 31. Whitlock G, McCormack C, Fearnley J, et al. High HIV incidence in men who have sex with men attending for postexposure prophylaxis: a service evaluation. Sex Transm Infect. 2016; 93:214–216. 32. Hyman S, Vittinghoff E, Irving R, et al. Sex pro: a personalized HIV risk assessment tool for men who have sex with men. Presented at: Conference on Retroviruses and Opportunistic Infections; February 23-26, 2015; Seattle. 33. Tan DHS, Leon-Carlyle M, Mills R, et al. Self-administered screening for syndemic mental health problems should be routinely implemented among MSM PrEP users. J Gay Lesbian Ment Health. 2016; 20:13–20. 34. Pathela P, et al. HIV incidence among men with and those without sexually transmitted rectal infections: estimates from matching against an HIV case registry. Clin Infect Dis. 2013;57:1203–1209. Use of Index Patients to Enable Home-Based Testing in Lesotho

Depressive symptoms and hazardous/harmful alcohol use are prevalent and correlate with stigma among TB-HIV patients in Lesotho

SETTING Twelve health facilities in Berea District, Lesotho, that participated in the Start TB Patients on ART and Retain on Treatment (START) Study, a mixed-methods cluster-randomized trial evaluating a combination intervention package to improve early initiation of antiretroviral therapy (ART) and anti-tuberculosis treatment success among patients with tuberculosis (TB) and human immunodeficiency virus (HIV). OBJECTIVE To assess TB and HIV diagnostic practices among TB-HIV patients. DESIGN A standardized survey assessed services at each facility at baseline. Routine clinical data were abstracted for all newly registered adult TB-HIV patients during the study period. Descriptive statistics were used to assess TB diagnostic practices, timing of the HIV diagnosis, and ART status at TB treatment initiation. RESULTS Between April 2013 and March 2015, 1233 TB-HIV patients were enrolled. Among 1215 patients with available data, 87.2% had pulmonary TB, of which 34.8% were bacteriologically confirmed, 40.9% tested negative and 24.3% were not tested. Among 1138 patients with available data, 53.3% had an existing HIV diagnosis, of whom 39.3% were ART-naïve. CONCLUSIONS The majority of pulmonary TB patients were clinically diagnosed, and many were unaware of their HIV status or were ART-naïve despite known status. The Test and Treat Strategy holds promise to prevent TB and reduce TB-related mortality among people living with HIV; however, enhanced TB diagnostic capacity and improved HIV case detection are urgently needed.

Pediatric HIV Treatment Gaps in 7 East and Southern African Countries: Examination of Modeled, Survey, and Routine Program Data

SETTING Limited data exist on the prevalence and correlates, including stigma, of mental health conditions, including depressive symptoms and alcohol use, among patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) in sub-Saharan Africa, despite their negative impact on health outcomes. OBJECTIVE To assess the prevalence and correlates of depressive symptoms and hazardous/harmful alcohol use among TB-HIV patients in the Start TB patients on ART and Retain on Treatment (START) study. DESIGN START, a mixed-methods cluster-randomized trial, evaluated a combination intervention package vs. standard of care (SOC) to improve treatment outcomes in TB-HIV co-infected patients in Lesotho. Moderate/severe depressive symptoms and hazardous/harmful alcohol use were measured using baseline questionnaire data collected from April 2013 to March 2015. Demographic, psychosocial, and TB- and HIV-related knowledge and attitudes, including stigma, were assessed for association with both conditions using generalized linear mixed models. RESULTS Among 371 participants, 29.8% reported moderate/severe depressive symptoms, and 24.7% reported hazardous/harmful alcohol use; 7% reported both. Depressive symptoms were significantly associated with less education, more difficulty understanding written medical information, non-disclosure of TB, greater TB stigma, and the SOC study arm. Hazardous/harmful alcohol use was significantly associated with male sex, as well as greater TB and external HIV stigma. CONCLUSION Prevalence of depressive symptoms and hazardous/harmful alcohol use were high, suggesting a need for routine screening for, and treatment of, mental health disorders in TB-HIV patients.