Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda.

BACKGROUND: Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the "TB consilium") to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019. METHODS: We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed. RESULTS: Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and "observation while on current regimen" (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed. CONCLUSION: Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important "gatekeepers" for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.

Prevalence of Biomarkers and Associated Factors for Chronic Kidney Disease in Adult Diabetic Out-patients in a Tertiary Hospital in Eastern Uganda - a Cross-sectional Study.

Background: Chronic kidney disease (CKD) is one of the most common complications of Diabetes Mellitus (DM). DM contributes to about 66% of CKD cases globally. CKiiiD results in increased morbidity and mortality and advanced stages often require renal replacement therapy that is unaffordable for the majority of the patients. Developing countries have scanty data regarding CKD burden in diabetic patients. OBJECTIVES: This study aimed at determining the prevalence of biomarkers for CKD and associated factors among diabetic patients attending the adult diabetic clinic of Mbale Regional Referral Hospital (MRRH). Methods: A cross-sectional study was conducted at the adult diabetic clinic of Mbale Regional Referral Hospital in Eastern Uganda. 374 adult diabetic patients who consented, were recruited and interviewed. A urine sample for Urine Albumin Creatinine Ratio (UACR) determination and a venous blood sample for measurement of serum creatinine were obtained from each participant. The estimated glomerular filtration rate (eGFR) was determined using the CKD-EPI equation and CKD was staged according to the Kidney Disease Improving Global Outcomes (KDIGO) systems. Results: A total of 318 (85%) participants had an eGFR of ≤ 60mls/min/1.72m2, significant proteinuria, or both. 6.1% were aware. Age, Duration of DM, Hypertension, and Dyslipidemia were associated with CKD biomarkers. Conclusion: There is a high prevalence of biomarkers for CKD among DM patients, the majority of them being undiagnosed. Over half of the DM patients had an eGFR consistent with advanced CKD. Strengthening routine screening for CKD biomarkers and enhancing the DM clinics with more diagnostic resources is recommended.

Prevalence, Awareness, and Factors Associated with Hypertension Among People Living with HIV in Eastern Uganda. A Multicentre Cross-Sectional Study.

Introduction: Despite advancements in Antiretroviral Therapy (ART), people living with HIV (PLHIV) face increasing risks of HTN, leading to significant morbidity and premature mortality, undermining the hard-earned gains of fighting HIV. The prevalence of hypertension among HIV patients and associated risk factors has not been extensively studied in the rural parts of Uganda. Objective: We assessed the prevalence, awareness, and factors associated with hypertension among PLHIV at two health facilities in Eastern Uganda. Methods: A cross-sectional study was conducted at Mbale Regional Referral Hospital and Bugobero Health Center IV HIV clinics from May to July 2023. We recruited patients with HIV above the age of 18 years and willing to consent. Participants were interviewed using a structured questionnaire adapted from the WHO STEPwise approach to noncommunicable disease risk factor surveillance (STEPS) and the AIDS Clinical Trials Group. Anthropometric measurements and blood pressure were taken. Bivariate and multivariable logistic regression were performed. A P value <0.2 in the bivariate analysis was transferred to the multivariable logistic regression model. A P value < 0.05 was statistically significant. Results: The study surveyed 400 PLHIV with a mean age of 46.5 (SD: 12.4) years; most were female (n=261, 65.3%). Hypertension prevalence was at 37.5%, with 20.5% in stage 2 and 68% ((n=102) of hypertensive participants were unaware. Hypertension was associated with age ≥50 years (aOR: 2.11, 95% CI: 1.33-3.37, p = 0.002), a suppressed viral load (aOR: 3.71, 95% CI: 1.02-5.13, p = 0.046) and BMI ≥25 Kg/m2 (aOR: 1.64, 95% CI: 1.01-2.66, p = 0.044). Conclusion: Hypertension is a significant burden among PLHIV in Eastern Uganda, influenced by HIV and lifestyle-related risk factors. Improved screening and diagnosis are needed with close monitoring for patients with viral load suppression due to the possible negative effects of ART on blood pressure.

This study explored the prevalence, awareness, and risk factors linked to high blood pressure among people living with HIV (PLHIV) at two health facilities in Eastern Uganda. We found that 37.5% of the participants had high blood pressure, yet the majority (68%) were unaware of their condition. We identified older age ≥50 years, a higher body mass index (BMI) ≥ 25 kg/m², and having a suppressed viral load as significant risk factors for high blood pressure among PLHIV. These results reveal the urgent need for improved health strategies that integrate the management of HIV and hypertension and preventive care to enhance the overall health outcomes for PLHIV in rural areas.

Prevalence and Factors Associated With Cryptoccocal Antigenemia Among Patients With Advanced Human Immunodeficiency Virus in Eastern Uganda: A Facility-Based Cross-sectional Study.

Background: Cryptoccocal infection remains an important cause of morbidity and mortality among people with advanced human immunodeficiency virus disease (AHD). In resource-limited settings, there is a paucity of data on cryptoccocal infections. We described the prevalence and factors associated with cryptoccocal antigenemia among people with AHD in Mbale Regional Referral Hospital in Eastern Uganda. Methods: In this cross-sectional study, data on sociodemographic, clinical, and laboratory characteristics of adults with AHD were collected, and factors associated with cryptoccocal antigenemia were determined using multivariate logistic regression models. Results: We enrolled 228 participants with a median CD4 cell count of 194/µL (interquartile range, 129-370/µL). The prevalence of cryptoccocal antigen was 10 in 228 (4.4% [95% confidence interval, 2.4%-80%]). CD4 cell counts <100/µL (adjusted odds ratio, 3.70) and poultry keeping were risk factors. The main predictors were headaches (adjusted odds ratio, 1), neck pains (8.817), confusion (6.323), and neck stiffness (676.217). No notable significant associations were found in the multivariate analysis. Conclusions: The prevalence of cryptoccocal antigen was 4.4%, and antiretroviral therapy was protective.

Mortality rate and associated factors among patients co-infected with drug resistant tuberculosis/HIV at Mulago National Referral Hospital, Uganda, a retrospective cohort study.

Drug resistant tuberculosis (DR-TB)/HIV co-infection remains a growing threat to public health and threatens global TB and HIV prevention and care programs. HIV is likely to worsen the outcomes of DR-TB and DR-TB is likely to worsen the outcomes of HIV despite the scale up of TB and HIV services and advances in treatment and diagnosis. This study determined the mortality rate and factors associated with mortality among persons on treatment co-infected with drug resistant TB and HIV at Mulago National Referral Hospital. We retrospectively reviewed data of 390 persons on treatment that had a DR-TB/HIV co-infection in Mulago National Referral Hospital from January 2014 to December 2019.Modified poisson regression with robust standard errors was used to determine relationships between the independent variables and the dependent variable (mortality) at bivariate and multivariate analysis. Of the 390 participants enrolled, 201(53.9%) were males with a mean age of 34.6 (±10.6) and 129 (33.2%,95% CI = 28.7-38.1%) died. Antiretroviral therapy(ART) initiation (aIRR 0.74, 95% CI = 0.69-0.79), having a body mass index (BMI)≥18.5Kg/m2 (aIRR 1.01, 95% CI = 1.03-1.17), having a documented client phone contact (aIRR 0.85, 95% CI = 0.76-0.97), having a mid-upper arm circumference,(MUAC) ≥18.5cm (aIRR 0.90, 95% CI = 0.82-0.99), being on first and second line ART regimen (aIRR 0.83, 95% CI = 0.77-0.89),having a known viral load (aIRR 1.09, 95% CI = 1.00-1.21) and having an adverse event during the course of treatment (aIRR 0.88, 95% CI = 0.83-0.93) were protective against mortality. There was a significantly high mortality rate due to DR-TB/HIV co-infection. These results suggest that initiation of all persons living with HIV/AIDS (PLWHA) with DR-TB on ART and frequent monitoring of adverse drug events highly reduces mortality.

Prevalence of Intestinal Helminth Coinfection in Drug-Resistant Tuberculosis in Uganda.

Background: Although a third of people with tuberculosis (TB) are estimated to be coinfected with helminths, the prevalence is largely unknown among people with drug-resistant TB (DR-TB). We determined the prevalence of helminth coinfection among people with DR-TB in Uganda. Methods: In a multicenter, cross-sectional study, eligible Ugandan adults with confirmed DR-TB were consecutively enrolled between July to December 2021 at 4 treatment centers. Sociodemographic data were collected using a questionnaire. Participants underwent anthropometric and blood pressure measurements, and blood samples were evaluated for random blood glucose, glycated hemoglobin, nonfasting lipid profile, human immunodeficiency virus (HIV) infection, and a complete blood count. Fresh stool samples were evaluated for adult worms, eggs, and larvae using direct microscopy after Kato-Katz concentration techniques. Results: Of 212 participants, 156 (73.6%) were male, 118 (55.7%) had HIV, and 3 (2.8%) had malaria coinfection. The prevalence of intestinal helminth coinfection was 4.7% (10/212) (95% confidence interval, 2.6%-8.6%). The frequency of helminth infections was Ancylostoma duodenale (n = 4), Schistosoma mansoni (n = 2), Enterobius vermicularis (n = 2), Ascaris lumbricoides (n = 1), and Trichuris trichiura (n = 1). Conclusions: The prevalence of helminth coinfection was low among people with DR-TB. More studies are needed to determine the clinical relevance of helminth/DR-TB coinfection.

Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study.

BACKGROUND: Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR - TB). This study aimed at determining the treatment outcomes of DR - TB patients with poor prognostic indicators in Uganda. METHODS: We reviewed treatment records of DR - TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR - TB, a treatment outcome in 2014-2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. RESULTS: Of 1122 DR - TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0-45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39-0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12-0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05-0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08-0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30-2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. CONCLUSION: Among DR - TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR - TB patients needs to be evaluated by prospective studies. DR - TB programs should also optimise DR - TB treatment the first time it is initiated.

High Prevalence of Rifampicin Resistance Associated with Rural Residence and Very Low Bacillary Load among TB/HIV-Coinfected Patients at the National Tuberculosis Treatment Center in Uganda.

BACKGROUND: Rifampicin resistance (RR) is associated with mortality among tuberculosis (TB) patients coinfected with HIV. We compared the prevalence of RR among TB patients with and without HIV coinfection at the National Tuberculosis Treatment Center (NTTC) in Uganda, a TB/HIV high burdened country. We further determined associations of RR among TB/HIV-coinfected patients. METHODS: In this secondary analysis, we included adult (≥18 years) bacteriologically confirmed TB patients that were enrolled in a cross-sectional study at the NTTC in Uganda between August 2017 and March 2018. TB, RR, and bacillary load were confirmed by the Xpert® MTB/RIF assay in the primary study. A very low bacillary load was defined as a cycle threshold value of >28. We compared the prevalence of RR among TB patients with and without HIV coinfection using Pearson's chi-square test. We performed logistic regression analysis to determine associations of RR among TB/HIV-coinfected patients. RESULTS: Of the 303 patients, 182 (60.1%) were male, 111 (36.6%) had TB/HIV coinfection, and the median (interquartile range) age was 31 (25-39) years. RR was found among 58 (19.1%) patients. The prevalence of RR was 32.4% (36/111) (95% confidence interval (CI): 24-42) among TB/HIV-coinfected patients compared to 11.5% (22/192) (95% CI: 7-17) among HIV-negative TB patients (p < 0.001). Among TB/HIV-coinfected patients, those with RR were more likely to be rural residents (adjusted odds ratio (aOR): 5.24, 95% CI: 1.51-18.21, p = 0.009) and have a very low bacillary load (aOR: 13.52, 95% CI: 3.15-58.08, p < 0.001). CONCLUSION: There was a high prevalence of RR among TB/HIV-coinfected patients. RR was associated with rural residence and having a very low bacillary load among TB/HIV-coinfected patients. The findings highlight a need for universal access to drug susceptibility testing among TB/HIV-coinfected patients, especially in rural settings.

Sustainability of the streamlined ART (START-ART) implementation intervention strategy among ART-eligible adult patients in HIV clinics in public health centers in Uganda: a mixed methods study.

BACKGROUND: Despite increasing access to antiretroviral therapy (ART), the proportion of eligible patients initiated on treatment remains suboptimal. Only 64.6% of the people living with HIV (PLHIV) globally were initiated on ART by June 2019. The streamlined ART (START-ART) implementation study was based on the PRECEDE model, which suggests that "predisposing, enabling, and reinforcing" factors are needed to create behavior change. START-ART increased ART initiation within 2 weeks of eligibility by 42%. However, the gains from some implementation interventions erode over time. We evaluated facilitators and barriers to sustainability of this streamlined ART initiation in the year following the implementation period. METHODS: We designed a mixed-methods explanatory sequential study to examine the sustainability of START-ART implementation. Quantitative component consisted of cross-sectional patient chart reviews of routinely collected data; qualitative component consisted of key informant interviews of health workers in START-ART facilities 2 years after conclusion of the implementation period. We analyzed data from 15 public health centers of Mbarara district, where the START-ART implementation was carried out. We included PLHIV aged > 18 years who initiated ART from June 2013 to July 2016. The START-ART implementation took place from June 2013 to June 2015 while the sustainability period was from August 2015 to July 2016. RESULTS: A total of 863 ART-eligible patients were sampled. The median CD4 count was 348 cells/ml (IQR 215-450). During the intervention, 338 (77.4%) eligible patients initiated on ART within 2 weeks compared with 375 (88.2%) during the sustainability period (risk difference 10.8%; 95% CI 5.9-15.8%). In 14 of the 15 health centers, the intervention was sustained. During key informant interviews, rapid ART initiation sustainability was attributed to counseling skills that were obtained during intervention and availability of point-of-care (POC) CD4 PIMA machine. Failure to sustain the intervention was attributed to three specific barriers: lack of training after the intervention, transfer of trained staff to other health facilities, and shortage of supplies like cartridges for POC CD4 PIMA machine. CONCLUSION: Rapid ART initiation was sustained in most health centers. Skills acquired during the intervention and functional POC CD4 machine facilitated while staff transfers and irregular laboratory supplies were barriers to sustainability of rapid ART initiation.

Closing the gap: A novel metric of change in performance.

BACKGROUND: Interventions to improve performance of global programs in the HIV cascade of care are widespread and increasing the focus of implementation science. At present, however, there is no clear consensus on how to conceptualize their improvement at the program level. The commonly used measures of association, based on ratios of probabilities (or odds), have well-known defects in public health applications. They yield large effect sizes even when the absolute effects, and therefore the public health impact, are small. On the other hand, risk differences create problems because settings with higher baseline values are penalized. We aim to examine ways of quantifying improvement in each health center of a cluster-randomized trial in Uganda to accelerate antiretroviral therapy initiation among HIV-infected adults. METHODS: We formalize the concept of the 'improvement index,' defined as the fraction of gaps closed as a metric of improvement, and suggest that it has unique features and strengths when compared to risk ratios and risk differences. RESULTS: Overall agreement between the different indices was not high, especially among health centers that were among the top 5 or 10. However, all ranking showed broad similarities at the far ends of the spectrum. On scatter plots, there was a positive linear relationship between the metrics, and the Bland Altman (B-A) plots were in agreement. CONCLUSION: The improvement index can be used as an alternative measure of association in implementation science interventions. It can be useful for public health purposes as it demonstrates how much can be covered from the baseline.

Virologic Response to First-line Efavirenz- or Nevirapine-based Antiretroviral Therapy in HIV-infected African Children.

BACKGROUND: Poorer virologic response to nevirapine- versus efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. METHODS: We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (P = 0.1). RESULTS: A total of 445 (53%) children received efavirenz and 391 (47%) nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5 years nevirapine, P < 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445 (2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P = 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus 26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36-48 weeks) virologic suppression <80 copies/mL was superior with efavirenz, particularly in children with higher pre-ART VL (P = 0.0004); longer-term suppression was superior with nevirapine in older children (P = 0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (P = 0.05). Results were broadly similar for <400 and <1000 copies/mL. CONCLUSION: Short-term VL suppression favored efavirenz, but long-term relative performance was age dependent, with better suppression in older children with nevirapine, supporting World Health Organization recommendation that nevirapine remains an alternative NNRTI.

Understanding uptake of an intervention to accelerate antiretroviral therapy initiation in Uganda via qualitative inquiry.

INTRODUCTION: The Streamlined Antiretroviral Therapy Initiation Strategy (START-ART) study found that a theory-based intervention using opinion leaders to inform and coach health care providers about the risks of treatment delay, provision of point of care (POC) CD4 testing machines (PIMA) and reputational incentives, led to rapid rise in ART initiation. We used qualitative research methods to explore mechanisms of provider behaviour change. METHODS: We conducted in-depth interviews (IDIs) with 24 health care providers and nine study staff to understand perceptions, attitudes and the context of changes in ART initiation practices. Analyses were informed by the Theoretical Domains Framework. RESULTS: Rapid dissemination of new practices was enabled in the environmental context of an existing relationship based on communication, implementation and accountability between Makerere University Joint AIDS Program (MJAP), a Ugandan University-affiliated organization that provided technical oversight for HIV service delivery at the health facilities where the intervention was implemented, and a network of health facilities operated by the Uganda Ministry of Health. Coaching carried out by field coordinators from MJAP strengthened influence and informal accountability for carrying out the intervention. Frontline health workers held a pre-existing strong sense of professional identity. They were proud of attainment of new knowledge and skills and gratified by providing what they perceived to be higher quality care. Peer counsellors, who were not explicitly targeted in the intervention design, effectively substituted some functions of health care providers; as role models for successful ART uptake, they played a crucial role in creating demand for rapid ART initiation through interactions with patients. Point of care (POC) CD4 testing enabled immediate action and relieved providers from frustrations of lost or delayed laboratory results, and led to higher patient satisfaction (due to reduced costs because of ability to initiate ART right away, requiring fewer return trips to clinic). CONCLUSIONS: Qualitative data revealed that a multicomponent intervention to change provider behaviour succeeded in the context of strong institutional and individual relationships between a University-affiliated organization, government facilities, and peer health workers (who acted as a crucial link between stakeholders) and the community. Fostering stable institutional relationships between institutional actors (non-governmental organization (NGOs) and ministry-operated facilities) as well as between facilities and the community (through peer health workers) can enhance uptake of innovations targeting the HIV cascade in similar clinical settings.

Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial.

BACKGROUND: In Africa, up to 30% of HIV-infected patients who are clinically eligible for antiretroviral therapy (ART) do not start timely treatment. We assessed the effects of an intervention targeting prevalent health systems barriers to ART initiation on timing and completeness of treatment initiation. METHODS: In this stepped-wedge, non-blinded, cluster-randomised controlled trial, 20 clinics in southwestern Uganda were randomly assigned in groups of five clinics every 6 months to the intervention by a computerised random number generator. This procedure continued until all clinics had crossed over from control (standard of care) to the intervention, which consisted of opinion-leader-led training and coaching of front-line health workers, a point-of-care CD4 cell count testing platform, a revised counselling approach without mandatory multiple pre-initiation sessions, and feedback to the facilities on their ART initiation rates and how they compared with other facilities. Treatment-naive, HIV-infected adults (aged ≥18 years) who were clinically eligible for ART during the study period were included in the study population. The primary outcome was ART initiation 14 days after first clinical eligibility for ART. This study is registered with ClinicalTrials.gov, number NCT01810289. FINDINGS: Between April 11, 2013, and Feb 2, 2015, 12 024 eligible patients visited one of the 20 participating clinics. Median CD4 count was 310 cells per µL (IQR 179-424). 3753 of 4747 patients (weighted proportion 80%) in the intervention group had started ART by 2 weeks after eligibility compared with 2585 of 7066 patients (38%) in the control group (risk difference 41·9%, 95% CI 40·1-43·8). Vital status was ascertained in a random sample of 208 patients in the intervention group and 199 patients in the control group. Four deaths (2%) occurred in the intervention group and five (3%) occurred in the control group. INTERPRETATION: A multicomponent intervention targeting health-care worker behaviour increased the probability of ART initiation 14 days after eligibility. This intervention consists of widely accessible components and has been tested in a real-world setting, and is therefore well positioned for use at scale. FUNDING: National Institute of Allergy and Infectious Diseases (NIAID) and the President's Emergency Fund for AIDS Relief (PEPFAR).

Young HIV-infected children and their adult caregivers prefer tablets to syrup antiretroviral medications in Africa.

BACKGROUND: Provision of anti-retroviral therapy (ART) for HIV-infected children is complicated using syrup formulations, which are costlier than tablets, harder to transport and store and difficult for health-workers to prescribe and caregivers to administer. Dispersible/crushable tablets may be more appropriate. We studied the acceptability of syrups and scored tablets among young children who used both in the AntiRetroviral Research fOr Watoto (ARROW) trial. METHODS: ARROW is an ongoing randomized trial of paediatric ART monitoring and treatment strategies in 1206 children in Uganda and Zimbabwe. 405 children initially received syrups of combination ART including Nevirapine, Zidovudine, Abacavir and Lamivudine before changing, when reaching the 12-<15 kg weightband, to scored adult-dose tablets prescribed according to WHO weightband tables. Caregiver expectations and experiences were collected in questionnaires at their last visit on syrups and after 8 and 24 weeks on tablets. RESULTS: Questionnaires were completed by caregivers of 267 children (median age 2.9 years (IQR 2.5, 3.4)). At last visit on syrups, 79% caregivers reported problems with syrups, mostly related to number, weight, transportation and conspicuousness of bottles. Difficulties taking tablets were expected by 127(48%) caregivers; however, after 8 and 24 weeks, only 26% and 18% reported their children had problems with tablets and no problems were reported with transportation/conspicuousness. Taste, swallowing or vomiting were reported as problems 'sometimes/often' for 14%, 9%, 22% children on syrups and 16%, 9%, 8% on tablets. At last visit on syrups, 74% caregivers expected to prefer tablets but only 27% thought their child would. After 8/24 weeks, 94%/97% caregivers preferred tablets and 57%/59% reported their child did. CONCLUSIONS: Most children at about 3 years can take tablets; caregivers and children themselves generally prefer tablets to liquid formulations of HIV medications above this age. Preferences of caregivers and children should be considered when designing and licensing paediatric drug formulations.