From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults.

HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes. Between July 2013 and August 2014, 953 individuals were enrolled, 119 (12.5%) had HIV-RNA ≥1000 copies/ml and 110 were successfully genotyped; 74 (67.3%) were on first-line and 36 (32.7%) on second-line ART regimens. The predominant HIV-1 subtypes were D (34.5%), A (33.6%) and Recombinant forms (21.8%). The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested. In resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load monitoring, targeted HIV drug resistance testing and availability of third-line ART regimens

“After all, we are all sick”: Multi-stakeholder understandings of stigma associated with integrated management of HIV, Diabetes and Hypertension at selected government clinics in Uganda.

Background: Integrated care is increasingly used to manage chronic conditions. In Uganda, the integration of HIV, diabetes and hypertension care has been piloted leveraging the well facilitated and established HIV health care provision structures. This qualitative study aimed to investigate the perceptions and experiences of patients, health care providers, clinical researchers, representatives from international NGOs, community members/leaders and policy makers on integrated management of HIV, diabetes and hypertension at selected government clinics in Central Uganda. Methods: We adopted a qualitative-observational design and participants were purposively selected. In-depth interviews were conducted with patients and with health care providers, clinical researchers, policy makers, and representatives from international NGOs. Focus group discussions were conducted with community members and leaders. Clinical procedures in the integrated care clinic were also observed. Data were managed using Nvivo 12 and analyzed thematically. Results: Triangulated findings revealed perceptions of integration reducing the frequency with which patients with comorbidities (HIV, diabetes, hypertension) visited health facilities, reduced the associated treatment costs, increased interpersonal relationships among patients and healthcare providers, and promoted capacity of health care providers to manage multiple chronic conditions. Integration also reduced stigma mainly through creating opportunities for health education, which allayed patient fears and increased their resolve to enroll for and adhere to treatment. Patients also had an opportunity to offer and receive psycho-social support and coupled with the support they received from healthcare workers, this strengthened the patient-patient relationship and provider-patient relationship, one of the building blocks of integration. Although, the integrated model significantly reduced stigma in general, it did not eradicate service level challenges and societal discrimination among HIV patients. Conclusion: The study narratives reveal that, in low resource settings like Uganda, integration of HIV, diabetes and hypertension care has potential to support patient experiences of co-morbid care. Integrated clinics may function as a central stigma mitigation strategy, operating independently of existing clinics and treating a range of conditions including HIV and other STIs

Decentralising chronic disease management in sub-Saharan Africa: a protocol for the qualitative process evaluation of community-based integrated management of HIV, diabetes and hypertension in Tanzania and Uganda

Introduction: Sub Saharan Africa continues to experience a syndemic of human immunodeficiency virus (HIV) and non-communicable diseases (NCDs). Vertical (stand-alone) HIV programming has provided high-quality care in the region, with almost 80% of people living with HIV in regular care, and 90% virally suppressed. Whilst integrated health education and concurrent management of HIV, hypertension and diabetes is being scaled up in clinics, innovative, more efficient and cost-effective interventions which include decentralisation into the community are required to respond to increased burden of co-morbid HIV/NCD disease. Methods and analysis: This protocol describes procedures for a process evaluation running concurrently with a pragmatic cluster-randomized trial (INTE-COMM) in Tanzania and Uganda which will compare community-based integrated care (HIV, diabetes, hypertension) with standard facility-based integrated care. The INTE-COMM intervention will manage multiple conditions (HIV, hypertension, diabetes) in the community via health monitoring and adherence/lifestyle advice (medicine, diet, exercise) provided by community nurses and trained lay-workers, and the devolvement of NCD drug dispensing to community level. Based on Bronfenbrenner’s ecological systems theory, the process evaluation will use qualitative methods to investigate socio-structural factors shaping care delivery and outcomes in up to 10 standard care facilities and/or intervention community sites with linked healthcare facilities. Multi-stakeholder interviews (patients, community health workers/volunteers, healthcare providers, policymakers, clinical researchers, international and non-governmental organisations), focus group discussions (community leaders, members) and non-participant observations (community meetings, drug dispensing) will explore implementation from diverse perspectives at three timepoints in the trial implementation. Iterative sampling and analysis moving between data collection points and data analysis to test emerging theories will continue under saturation is reached. This process of analytic reflexivity and triangulation across methods and sources will provide findings to explain the main trial findings and offer clear directions for future efforts to sustain and scale up community-integrated care for HIV, diabetes and hypertension

Integrating HIV, Diabetes, and Hypertension services in Africa: study protocol for a cluster randomized trial in Tanzania and Uganda.

Introduction: HIV programmes in sub-Saharan Africa are well-funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Health care provision is organised from stand-alone clinics. In this cluster-randomised trial, we are evaluating a concept of integrated care for people with HIV-infection, diabetes or hypertension from a single point of care. Methods and Analysis: 32 primary care health facilities in Dar es Salaam and Kampala regions were randomised to either integrated or standard vertical care. In the integrated care arm, services are organised from a single clinic where patients with either HIV-infection, diabetes, or hypertension are managed by the same clinical and counselling teams. They use the same pharmacy and laboratory and have the same style of patient records. Standard care involves separate pathways, i.e. separate clinics, waiting and counselling areas, a separate pharmacy and separate medical records. The trial has 2 primary endpoints: retention in care of people with hypertension or diabetes and plasma viral load suppression. Recruitment is expected to take 6 months and follow-up is for 12 months. With 100 participants enrolled in each facility with diabetes or hypertension, the trial will provide 90% power to detect an absolute difference in retention of 15% between the study arms (at the 5% two-sided significance level). If 100 participants with HIV-infection are also enrolled in each facility, we will have 90% power to show non-inferiority in virological suppression to a delta=10% margin (i.e. that the upper limit of the one-sided 95% confidence interval of the difference between the two arms will not exceed 10%). To allow for loss to follow-up, the trial will enrol over 220 persons per facility. This is the only trial of its kind evaluating the concept of a single integrated clinic for chronic conditions in Africa Ethics and Dissemination: The protocol has been approved by ethics committee of The AIDS Support Organisation, National Institute of Medical Research and the Liverpool School of Tropical Medicine. Dissemination of findings will be done through journal publications and meetings involving study participants, health care providers and other stakeholders. Trial registration: ISRCTN43896688 Strengths of this trial • This is the largest trial of its kind with replication in over 30 health facilities and 2 countries. • It was designed, implemented and is being monitored in partnership with patient representatives, health care providers, policy makers and other stakeholders. • The trial is measuring objective markers of effectiveness and is multidisciplinary. Limitations of this trial • The trial has a relatively short follow-up of 12 months and cannot estimate effect against mortality or other longer-term outcomes. • The trial cannot be blinded – both health care providers and patients know the intervention being delivered at each health facility

Ethical issues in intervention studies on the management of treatment of diabetes and hypertension in sub-Saharan Africa.

The incidence of diabetes and hypertension has risen sharply in sub-Saharan Africa alongside a continuing high burden of HIV-infection. In many settings, the prevalence figures among adults are 4-5% for diabetes, above 25% for hypertension and 5-20% for HIVinfection. All these conditions require life-long treatment and they have increased substantially the demand for chronic care services in Africa, where health systems have, until recently, focussed on tackling acute infectious diseases

Integrated management of HIV, diabetes and hypertension in sub Saharan Africa: a pragmatic multi-country cluster-randomised trial

Introduction: In Africa, health care provision for chronic conditions is fragmented. We evaluated integrated management of HIV, diabetes and hypertension in Dar es Salaam, Tanzania and Kampala, Uganda. Methods: We conducted a pragmatic, cluster-randomised trial. Primary health care facilities were randomised to provide either integrated or standard care. In integrated care, participants with HIV, diabetes or hypertension were managed by the same healthcare workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting area and had an integrated laboratory service. In standard care , these services were delivered vertically for each condition. Analyses used Generalised Estimating Equations. Recruitment was between 30th June 2020 and 1st April 2021 and follow-up was for 12 months. This trial is registered: ISCRTN 43896688. Findings: 32 health facilities were randomised. Just 3% of patients declined to join. Among participants with diabetes, hypertension or both, mean age (standard deviation) was 60.1 (12.7) years in the integrated care arm and 57.7 (12.2) in the standard care arm; among participants with HIV, these figures were 42.6 (11.2) and 42.7 (10.8) respectively. Among participants with diabetes, hypertension or both, the proportion alive and retained in care at study end was 1254/1409 (89.0%) in integrated care and 1457/1623 (89.8%) in standard care. The differences (95% CI were -0.65% (-5.76, 4.46; p=0.80) unadjusted and - 0.60% (-5.46, 4.26; p=0.81) adjusted. Among participants with HIV, the proportion who had plasma viral load <1,000 copies per ml was 1412/1456 (97.0%) in integrated care and 1451/1491 (97.3%) in standard care. The differences were -0.37% (One-sided 95% CI -1.99, 1.26; p-value for non-inferiority <0.0001 unadjusted) and -0.36% (-1.99, 1.28; p-value for non-inferiority <0.0001 adjusted). Conclusion: In sub-Saharan Africa, integrated chronic care services could improve outcomes for people with diabetes or hypertension without adversely affect outcomes for people with HIV