Incidence and determinants of adverse events in individuals with HIV commencing Dolutegravir-based antiretroviral therapy in mainland Tanzania.

Tanzania adopted a Dolutegravir (DTG)-based regimen as first-line treatment in 2019 following the World Health Organization recommendation. Data on the DTG safety profile from sub-Saharan Africa including Tanzania are limited. We investigated the incidence of DTG-related adverse events (AEs) and associated factors among people living with HIV (PLHIV) initiated on a DTG regimen. A prospective cohort study was conducted from 25 Care and Treatment Clinics in mainland Tanzania. PLHIV aged 12 years and above who were initiated on a DTG-based regimen were actively followed up for three months. The Cox regression model was used to determine the predictors of occurrence of AEs over time. A p-value of 0.05 was considered statistically significant. From January 2020 to June 2022, a cohort of 935 participants who were both newly diagnosed and ART-experienced who transitioned to a DTG-based regimen was enrolled. Out of 935 participants, 59 (6.3%) reported a total of 62 AEs. The most frequently experienced AE was skin itching and rashes (15/62; 24.2%). DTG-associated neuropsychiatric AEs were less common and included headache (6 [9.6%]) and sleep disturbances (3 [4.8%]). The overall incidence of occurrence of the first AEs was 96.7 per 1000 person-months [95% C.I: 74.4-125.7] with the highest incidence observed among the elderly (≥ 60 years). Individuals on WHO HIV Clinical Stage 2 had a 2.7 significantly higher risk of developing AEs (adjusted hazard ratio = 2.73, 95% CI = 1.46-5.12, p = 0.017). We report a low incidence of grade I (mild) and grade II (moderate) DTG-associated AEs suggesting that the regimen is generally safe in the population. Continued monitoring of DTG safety in the population is recommended.

Malaria elimination in Zanzibar: where next?

In 2018, Zanzibar developed a national malaria strategic plan IV (2018-2023) to guide elimination of malaria by 2023. We assessed progress in the implementation of malaria activities as part of the end-term review of the strategic plan. The review was done between August and October 2022 following the WHO guideline to assess progress made towards malaria elimination, effectiveness of the health systems in delivering malaria case management; and malaria financing. A desk review examined available malaria data, annual work plans and implementation reports for evidence of implemented malaria activities. This was complemented by field visits to selected health facilities and communities by external experts, and interviews with health management teams and inhabitants to authenticate desk review findings. A steady increase in the annual parasite incidence (API) was observed in Zanzibar, from 2.7 (2017) to 3.6 (2021) cases per 1,000 population with marked heterogeneity between areas. However, about 68% of the detected malaria cases were imported into Zanzibar. Malaria case follow-up and investigation increased from <70% in 2017 to 94% and 96% respectively, in 2021. The review noted a 3.7-fold increase of the health allocation in the country's budget, from 31.7 million USD (2017/18) to 117.3 million USD (2022/23) but malaria allocation remained low (<1%). The varying transmission levels in the islands suggest a need for strategic re-orientation of the elimination attempts from a national-wide to a sub-national agenda. We recommend increasing malaria allocation from the health budget to ensure sustainability of malaria elimination interventions.

Accelerating HIV and AIDS services delivery in Kigoma region, Tanzania.

Introduction: Tanzania Commission for AIDS and UNAIDS reports 1.7 million Tanzanians are HIV-positive. The Joint United Nations Program on HIV/AIDS set 95%, 95% 95% targets to be achieved by 2025. An assessment was done to understand the region's position, which found the underperformance of critical HIV and AIDS indicators. This prompted the region to accelerate HIV interventions by providing frontline healthcare providers with skills and knowledge, essential equipment, and other infrastructure, after which the assessment of the indicators was conducted to document the outcome of interventions. Methods: we conducted a descriptive study in Kigoma region in June 2022 by comparing HIV and AIDS indicators performance in the pre-intervention and post interventions arms. High-volume CTCs were purposefully selected. We used a pre-tested checklist to assess new HIV-positive on antiretroviral (ARV), pregnant women living with HIV on ARV, and people living with HIV offered multi-month dispensing. We further assessed HIV viral load (HVL) specimen collection, HIV suppression status, and HVL test results turnaround time. We cleaned the information using an MS Excel sheet and tabulated results using STATA software version 13. Results: we assessed 27 care and clinics. The proportion gain in the index client elicitation was 13%. Sexual partners mentioned during index client elicitation had an increase of 145 individuals. The yield among consented sexual partners gained by 14%. The ARV initiation among new HIV -positive and pregnant women living with HIV gained a proportion of 2%. Multi-month dispencing was found to have an 8% increase. The turnaround time for HVL test results decreased by 21 days, and the viral load suppression status increased by 4%. Conclusion: the assessment demonstrated the accelerated HIV and AIDS service delivery due to implementing a comprehensive package of HIV and AIDS management. We recommend in-service capacity building regarding training, basic equipment, and infrastructure.

Low engagement of key populations in HIV health services in Tanzania: analysis of community, legal and policy factors.

Introduction: key populations (KP) often face legal and social challenges that increase their vulnerability to HIV. These experiences include criminalization, higher levels of stigma and discrimination which negatively affect access to HIV services. This study aims to understand legal, community and policy factors affecting engagement of KP in HIV health interventions. Methods: qualitative research key populations design involving a desk review and stakeholder's engagement. We reviewed program data from NACP on how KP access health services and then conducted three stakeholders' engagement meetings. Factors affecting access to health services by KP were documented. Data were organized using socio-ecological model (SEM). Results: program data showed only 49% of the estimated KP accessed health services. Barriers to accessing health services at the interpersonal level included lack of social support and high-risk networks linked with risk behaviours. At the community, stigma and discrimination, limited engagement of influential leaders were noted. In health facilities, lack of trained staff to provide KP friendly services affected utilization of health services. At structural level, despite improvements, still various laws negated engagement of KP such criminalizing drug use, same sex, and sex work. Harassments and arrests further marginalize KP and makes access to health intervention harder. Conclusion: engagement of key population into HIV health interventions was limited at multiple levels. The study recommends building capacity on KP friendly services for communities, law enforcement and health care providers, further engagement of communities including religious leaders on KP issues and implementing differentiated service delivery models for KP.

Process of developing Country Cooperation Strategy in Tanzania, as an effective tool for aligning WHO's support to the member state in achieving health and health-related sustainable development goal.

Introduction: an organization's long-term success and relevance are linked with compelling strategic development. To that end, the country office of WHO in the United Republic of Tanzania, in collaboration with stakeholders, developed a 6-year Country Cooperation Strategy (CCS), 2022-2027. This paper describes the various steps taken in developing the CCS for the United Republic of Tanzania. Methods: we reviewed the global guideline for the development of CCS. In addition, we analysed documents on the national health sector strategic plan, the 13th Global Program of Work for WHO (GPW13), and the Sustainable Development Goal (SDG). We also reviewed data from routine HMIS, the Global Burden of Disease (GBD), and assessment results of the UN on the status of SDGs through the Common Country Assessment (CCA). Results: the performance on the overall Universal Health Coverage (UHC) effective coverage index, on a scale of 0-100, for Tanzania improved from 45.2 in 2010 to 55.2 in 2019. Strengthening health systems, protecting communities against public health emergencies, reducing or controlling exposure of individuals to risk factors, and better health governance, leadership, and accountability were the identified priorities for the CCS. Conclusion: the process of alignment of the CCS document with the national and global strategic goals would help the WHO to support and lead the country's effort towards achieving health-related SDGs. We believe the process we employed will lead to having detailed operational plans for implementation for achieving SDG targets. Keywords: Country cooperation strategy (CCS), sustainable development goal (SDG), strategic document, 13th global program of work (GPW13), health sector strategy, stakeholders, Tanzania.

Viral load testing among pregnant women living with HIV in Mutare district of Manicaland province, Zimbabwe.

BACKGROUND: Viral load (VL) monitoring of pregnant women living with HIV (PWLHIV) and antiretroviral therapy (ART) may contribute to lowering the risk of vertical transmission of HIV. The aims of this study were to assess the uptake of HIV VL testing among PWLHIV at entry to the prevention-of-mother-to-child transmission (PMTCT) services and identify facilitatory factors and barriers to HIV VL access. METHODS: A retrospective, cross-sectional study was conducted at 15 health facilities in Mutare district, Manicaland Province, Zimbabwe from January to December 2018. This analysis was complemented by prospective interviews with PWLHIV and health care providers between October 2019 and March 2020. Quantitative data were analysed using descriptive and inferential statistical methods. Risk factors were evaluated using multivariate logistic regression. Open-ended questions were analysed and recurring and shared experiences and perceptions of PWLHIV and health care providers identified. RESULTS: Among 383 PWLHIV, enrolled in antenatal care (ANC) and receiving ART, only 121 (31.6%) had a VL sample collected and 106 (88%) received their results. Among these 106 women, 93 (87.7%) had a VL < 1000 copies/mL and 77 (73%) a VL < 50 copies/mL. The overall median duration from ANC booking to VL sample collection was 87 (IQR, 7-215) days. The median time interval for the return of VL results from date of sample collection was 14 days (IQR, 7-30). There was no significant difference when this variable was stratified by time of ART initiation. VL samples were significantly less likely to be collected at local authority compared to government facilities (aOR = 0.28; 95% CI 0.16-0.48). Barriers to VL testing included staff shortages, non-availability of consumables and sub-optimal sample transportation. Turnaround time was prolonged by the manual results feedback system. CONCLUSIONS AND RECOMMENDATION: The low rate of HIV VL testing among PWLHIV in Mutare district is a cause for concern. To reverse this situation, the Ministry of Health should consider interventions such as disseminating antiretroviral guidelines and policies electronically, conducting regular PMTCT mentorship for clinical staff members, and utilising point of care testing and telecommunication devices like mHealth to increase uptake of VL testing and improve results turnaround time.

Antimicrobial susceptibility in Neisseria gonorrhoeae isolates from five sentinel surveillance sites in Zimbabwe, 2015-2016.

OBJECTIVES: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns worldwide. Enhanced AMR surveillance for gonococci is essential globally. In Zimbabwe, very limited gonococcal AMR data were reported. Our aims were to (i) implement quality-assured gonococcal AMR surveillance in Zimbabwe and (ii) investigate gonococcal AMR at five health centres in 2015-2016. METHODS: Gonococcal isolates from 104 men with urethral discharge were tested for susceptibility to kanamycin, ceftriaxone, cefixime, ciprofloxacin and azithromycin using Etest. RESULTS: All isolates (102 possible to test) were susceptible to ceftriaxone and cefixime. The level of resistance (intermediate resistance) to kanamycin and ciprofloxacin was 2.0% (2.0%) and 18.6% (27.5%), respectively. The two kanamycin-resistant isolates (R≥128 mg/L) had a kanamycin minimum inhibitory concentration (MIC) of >256 mg/L. The ciprofloxacin resistance ranged from 9.5% to 30.8% in the five sentinel sites. Only 10 (9.6%) of the isolates were tested for susceptibility to azithromycin and 1 (10.0%) was resistant (MIC=4 mg/L). CONCLUSIONS: The emergence of multidrug-resistant gonorrhoea internationally is a major public health concern and gonococcal AMR surveillance is crucial globally. In Zimbabwe, gonococcal AMR surveillance has now been implemented and quality assured according to WHO standards. The results of this first surveillance will be used to directly inform revisions of the national treatment guidelines. It is imperative to further strengthen the surveillance of gonococcal AMR, and ideally also treatment failures, in Zimbabwe and most countries in the WHO African region, which requires continuous national and international support, including technical support, and political and financial commitment.

Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis.

BACKGROUND: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. METHODS: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. RESULTS: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. CONCLUSIONS: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

Building Health System Capacity Through Implementation Research: Experience of INSPIRE-A Multi-country PMTCT Implementation Research Project.

BACKGROUND: The INSPIRE-Integrating and Scaling Up PMTCT through Implementation REsearch-initiative was established as a model partnership of national prevention of mother-to-child transmission of HIV (PMTCT) implementation research in 3 high HIV burden countries-Malawi, Nigeria, and Zimbabwe. INSPIRE aimed to link local research groups with Ministries of Health (MOH), build local research capacity, and demonstrate that implementation research may contribute to improving health care delivery and respond to program challenges. METHODOLOGY: We used a mixed methods approach to review capacity building activities, as experienced by health care workers, researchers, and trainers conducted in the 6 INSPIRE projects before and during study implementation. RESULTS: Between 2011 and 2016, over 3400 health care workers, research team members, and community members participated in INSPIRE activities. This included research prioritization exercises, proposal development, good clinical practice and research ethics training, data management and analysis workshops, and manuscript development. Health care workers in clinics and district health offices acknowledged the value of hosting implementation research projects and how the quality of services improved. Research teams acknowledged the opportunities that projects provided for personal development and the value of participating in a multicountry research network. DISCUSSION: INSPIRE provided an opportunity for African-led research in which researchers worked closely with national MOH to identify priority research questions and implement studies. Close partnerships between research teams and local implementers facilitated project responsiveness to local program issues. Consequently, processes and training needed for study implementation also improved local program management and service delivery. Additional benefits included improved data management, publications, and career development.

Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.

BACKGROUND: Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010. METHODS: Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites. RESULTS: A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002). CONCLUSIONS: The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Results from implementing updated 2012 World Health Organization Guidance on early-warning indicators of HIV drug resistance in Zimbabwe.

OBJECTIVE: This study evaluated the performance of sentinel sites in preventing the emergence of HIVDR using Early Warning Indicators (HIVDR EWI) survey. METHODS: Adult and paediatric patient data on: On time pill pick up, Retention in care, Pharmacy stock-outs, and Dispensing practices was collected. Information from pharmacy registers was verified using facility-held cards. This was a cross-sectional analysis of retrospectively collected data from 72 sites providing both adult and paediatric ART as well as two providing adult ART only. All data were entered into and analysed using a WHO EWI data abstraction electronic tool. RESULTS: Twenty-one percent of sites providing adult and 4.2% of sites providing paediatric ART managed to meet the target for on time pill pick up. Retention in care indicator was met by 48.7% (95% CI: 36.9-60.6) of sites. ARV stock-outs occurred in 81.1% (95% CI: 70-89.3) adult sites and 63.9% (95% CI: 50-78.6) paediatric sites. ARVs were appropriately dispensed by 86.5% (95% CI: 75.6-93.3) of adult sites and 84.7% (95% CI: 74.3-92.1) of paediatric sites. CONCLUSIONS: Most sites had low performance in many indicators in this survey and failed to meet the recommended targets. Some policies such as the current buffer stock and storage outside Harare should be revised in order to improve site access to ARVs. The country should prioritize the provision of viral load testing services in all provinces. The electronic patient management system should be rolled out to all ART sites to improve patient tracking and monitoring by sites.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Prioritizing the PMTCT implementation research agenda in 3 African countries: INtegrating and Scaling up PMTCT through Implementation REsearch (INSPIRE).

Countries with high HIV prevalence face the challenge of achieving high coverage of antiretroviral drug regimens interventions including for the prevention of mother-to-child transmission of HIV (PMTCT). In 2011, the World Health Organization and the Department of Foreign Affairs, Trade and Development, Canada, launched a joint implementation research (IR) initiative to increase access to effective PMTCT interventions. Here, we describe the process used for prioritizing PMTCT IR questions in Malawi, Nigeria, and Zimbabwe. Policy makers, district health workers, academics, implementing partners, and persons living with HIV were invited to 2-day workshops in each country. Between 42 and 70 representatives attended each workshop. Using the Child Health Nutrition Research Initiative process, stakeholder groups systematically identified programmatic barriers and formulated IR questions that addressed these challenges. IR questions were scored by individual participants according to 6 criteria: (1) answerable by research, (2) likely to reduce pediatric HIV infections, (3) addresses main barriers to scaling-up, (4) innovation and originality, (5) improves equity among underserved populations, and (6) likely value to policy makers. Highest scoring IR questions included health system approaches for integrating and decentralization services, ways of improving retention-in-care, bridging gaps between health facilities and communities, and increasing male partner involvement. The prioritized questions reflect the diversity of health care settings, competing health challenges and local and national context. The differing perspectives of policy makers, researchers, and implementers illustrate the value of inclusive research partnerships. The participatory Child Health Nutrition Research Initiative approach effectively set national PMTCT IR priorities, promoted country ownership, and strategically allocated research resources.