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.

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.

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.

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.

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.

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.