scholarly journals Impact of scaling up dolutegravir on antiretroviral resistance in South Africa: A modeling study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (12) ◽  
pp. e1003397
Author(s):  
Anthony Hauser ◽  
Katharina Kusejko ◽  
Leigh F. Johnson ◽  
Huldrych F. Günthard ◽  
Julien Riou ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Scale Up ◽  
Scaling Up ◽  
Reproductive Age ◽  
Childbearing Age ◽  
Genetic Barrier ◽  
Men And Women ◽  
Nnrti Resistance ◽  
The Impact

Background Rising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG’s high genetic barrier to resistance. We used mathematical modeling to predict the impact of the scale-up of DTG-based ART on NNRTI pretreatment drug resistance (PDR) in South Africa, 2020 to 2040. Methods and findings We adapted the Modeling Antiretroviral drug Resistance In South Africa (MARISA) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modeled the introduction of DTG in 2020 under 2 scenarios: DTG as first-line regimen for ART initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Given the safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to (1) women beyond reproductive age; (2) women beyond reproductive age or using contraception; and (3) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI PDR in all scenarios if ART initiators are started on a DTG-based regimen, and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI PDR would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI PDR from 52.4% (without DTG) to 10.4% (with universal DTG) in 2040. If only men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI PDR would reach 25.9% in 2040. Limitations include substantial uncertainty due to the long-term predictions and the current scarcity of knowledge about DTG efficacy in South Africa. Conclusions Our model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels, whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would only slow down the increase in levels of NNRTI PDR.

scholarly journals The Impact of Scaling up Dolutegravir on Antiretroviral Resistance in South Africa

2019 ◽  
Author(s):  
Anthony Hauser ◽  
Katharina Kusejko ◽  
Leigh F. Johnson ◽  
Huldrych F. Günthard ◽  
Julien Riou ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Scale Up ◽  
Scaling Up ◽  
Reproductive Age ◽  
Childbearing Age ◽  
Genetic Barrier ◽  
Men And Women ◽  
Nnrti Resistance ◽  
The Impact

AbstractBackgroundRising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG’s high genetic barrier to resistance. We used mathematical modelling to examine the impact of the scale-up of DTG-based ART on NNRTI pre-treatment drug resistance (PDR) in South Africa, 2019-2040.Methods and resultsWe adapted the MARISA (Modelling Antiretroviral drug Resistance In South Africa) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modelled the introduction of DTG in 2019 under two scenarios: DTG as first-line regimen for ART-initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Due to safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to i) women beyond reproductive age, ii) women beyond reproductive age or using contraception, and iii) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI resistance in all scenarios if both ART initiators are started on a DTG-based regimens and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI resistance would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI resistance from 58.5% (without DTG) to 14.8% (with universal DTG) in 2040. If all men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI resistance would reach 35.1% in 2040.ConclusionsOur model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would slow down the increase in levels of NNRTI resistance.

scholarly journals Investment case for two-year post university speciality training in family medicine in Tajikistan: how much is needed for continuing and scaling up the improved education of family doctors?

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jari Kempers ◽  
Leah F. Bohle ◽  
Alexandra Topa ◽  
Greta Ross ◽  
Zukhra Kasymova ◽  
...  
Keyword(s):  
Family Medicine ◽  
Clinical Skills ◽  
Scale Up ◽  
Scaling Up ◽  
Gradual Transition ◽  
Theoretical Knowledge ◽  
Family Doctors ◽  
International Support ◽  
Speciality Training ◽  
The Impact

Abstract Background A new two-year Post University Specialty Training (PUST) programme in family medicine was introduced to improve the quality of postgraduate speciality medical education in Tajikistan. Postgraduate education of family doctors (FDs) needs to be urgently scaled up, as 38% of FD positions in Tajikistan remained unfilled in 2018. Moreover, the international financial support for the PUST programme is ending. This investment case assesses the minimum funding needed for the continuation and scale-up of PUST and establishes the rationale for the investment in the light of a recent evaluation. Methods The costs of the programme were calculated for 2018 and a scale-up forecast made for the period 2019–2023. The impact of the scale-up on the shortage of FDs was assessed. An evaluation using a Multiple Choice Questionnaire and Objective Structured Clinical Examination (OSCE) assessed and compared theoretical knowledge, clinical skills and competencies of PUST trained and conventionally trained FDs. Results The annual costs of the programme were US$ 228,000 in 2018. The total investment needed for scaling up PUST from 31 new FDs in 2018 to 100 FD graduates each year by 2023 was US$ 802,000.However, when the retirement of FDs and population growth are considered, the scale-up will result only in maintaining the current level of FDs working and not solve the country’s FD shortage. The PUST FDs demonstrated significantly better clinical skills than the conventionally trained interns, scoring 60 and 45% of OSCE points, respectively. Theoretical knowledge showed a similar trend; PUST FDs answered 44% and interns 38% of the questions correctly. Conclusions The two-year PUST programme has clearly demonstrated it produces better skilled family doctors than the conventional one-year internship, albeit some enduring quality concerns do still prevail. The discontinuation of international support for PUST would be a major setback and risks potentially losing the benefits of the programme for family medicine and also other specialities. To guarantee the supply of adequately trained FDs and address the FD shortage, the PUST should be continued and scaled up. Therefore, it is essential that international support is extended and a gradual transition to sustainable national financing gets underway.

scholarly journals The impact of the program for medical male circumcision on HIV in South Africa: analysis using three epidemiological models

2021 ◽  
Vol 5 ◽  
pp. 15
Author(s):  
Eline L. Korenromp ◽  
Anna Bershteyn ◽  
Edina Mudimu ◽  
Renay Weiner ◽  
Collen Bonecwe ◽  
...  
Keyword(s):  
South Africa ◽  
Male Circumcision ◽  
Hiv Transmission ◽  
Scale Up ◽  
Household Survey ◽  
Hiv Infections ◽  
Treatment Needs ◽  
Medical Male Circumcision ◽  
Hiv Epidemic ◽  
The Impact

Background: South Africa began offering medical male circumcision (MMC) in 2010. We evaluated the current and future impact of this program to see if it is effective in preventing new HIV infections. Methods: The Thembisa, Goals and Epidemiological Modeling Software (EMOD) HIV transmission models were calibrated to South Africa’s HIV epidemic, fitting to household survey data on HIV prevalence, risk behaviors, and proportions of men circumcised, and to programmatic data on intervention roll-out including program-reported MMCs over 2009-2017. We compared the actual program accomplishments through 2017 and program targets through 2021 with a counterfactual scenario of no MMC program. Results: The MMC program averted 71,000-83,000 new HIV infections from 2010 to 2017. The future benefit of the circumcision already conducted will grow to 496,000-518,000 infections (6-7% of all new infections) by 2030. If program targets are met by 2021 the benefits will increase to 723,000-760,000 infections averted by 2030. The cost would be $1,070-1,220 per infection averted relative to no MMC. The savings from averted treatment needs would become larger than the costs of the MMC program around 2034-2039. In the Thembisa model, when modelling South Africa’s 9 provinces individually, the 9-provinces-aggregate results were similar to those of the single national model. Across provinces, projected long-term impacts were largest in Free State, KwaZulu-Natal and Mpumalanga (23-27% reduction over 2017-2030), reflecting these provinces’ greater MMC scale-up. Conclusions: MMC has already had a modest impact on HIV incidence in South Africa and can substantially impact South Africa’s HIV epidemic in the coming years.

scholarly journals Multiple pathways to scaling up and sustainability: An exploration of digital health solutions in South Africa

2020 ◽  
Author(s):  
Alison Swartz ◽  
Amnesty E LeFevre ◽  
Shehani Perera ◽  
Mary V. Kinney ◽  
Asha S George
Keyword(s):  
South Africa ◽  
Digital Health ◽  
National Level ◽  
Scale Up ◽  
Monitoring And Evaluation ◽  
Scaling Up ◽  
Value Proposition ◽  
Problem Identification ◽  
Human Resource Capacity ◽  
Organisational Context

Abstract Background With an aim to support further understanding of scaling up and sustaining digital health, we explore digital health solutions that have or are anticipated to reach national scale in South Africa: the Perinatal Problem Identification Programme and Child Healthcare Problem Identification Programme (mortality audit reporting and visualisation tools), MomConnect (a direct to consumer maternal messaging and feedback service) and CommCare (a community health worker data capture and decision-support application). Results A framework integrating complexity and scaling up processes was used to conceptually orient the study. Findings are presented by case through four domains: value proposition, actors, technology and organisational context. The scale and use of PPIP and Child PIP were driven by ‘champions’; clinicians who developed technically simple tools to digitise clinical audit data. Top-down political will at the national level drove the scaling of MomConnect, supported by ongoing financial and technical support from donors and technical partners. Donor preferences played a significant role in the selection of CommCare as the platform to digitise CHW service information, with a focus on HIV and TB. A key driver of scale across cases is leadership that recognises and advocates for the value of the digital health solution. The technology need not be complex but must navigate the complexity of operating within an overburdened and fragmented South African health system, where adequate and sustained investment from donors and government overall, and in particular in its human resource capacity and in robust monitoring and evaluation continue to threaten the sustainability of digital health solutions. Conclusions There is no single pathway to achieving scale up or sustainability, and there will be successes and challenges regardless of the configuration of the domains of value proposition, technology, actors and organisational context. While scaling and sustaining digital solutions has its technological challenges, perhaps more complex are the idiosyncratic factors and nature of the relationships between actors involved. Scaling up and sustaining digital solutions need to account for the interplay of the various technical and social dimensions involved in supporting digital solutions to succeed, particularly in health systems that are themselves social and political dynamic systems.

scholarly journals Reproductive Counseling by Clinic Healthcare Workers in Durban, South Africa: Perspectives from HIV-Infected Men and Women Reporting Serodiscordant Partners

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
L. T. Matthews ◽  
T. Crankshaw ◽  
J. Giddy ◽  
A. Kaida ◽  
C. Psaros ◽  
...  
Keyword(s):  
South Africa ◽  
Health Care ◽  
Behavioral Interventions ◽  
Unplanned Pregnancy ◽  
Reproductive Age ◽  
Safer Conception ◽  
Men And Women ◽  
Related Information ◽  
Patient Reported ◽  
Reproductive Counseling

Background. Understanding HIV-infected patient experiences and perceptions of reproductive counseling in the health care context is critical to inform design of effective pharmaco-behavioral interventions that minimize periconception HIV risk and support HIV-affected couples to realize their fertility goals.Methods. We conducted semistructured, in-depth interviews with 30 HIV-infected women (with pregnancy in prior year) and 20 HIV-infected men, all reporting serodiscordant partners and accessing care in Durban, South Africa. We investigated patient-reported experiences with safer conception counseling from health care workers (HCWs). Interview transcripts were reviewed and coded using content analysis for conceptual categories and emergent themes.Results. The study findings indicate that HIV-infected patients recognize HCWs as a resource for periconception-related information and are receptive to speaking to a HCW prior to becoming pregnant, but seldom seek or receive conception advice in the clinic setting. HIV nondisclosure and unplanned pregnancy are important intervening factors. When advice is shared, patients reported receiving a range of information. Male participants showed particular interest in accessing safer conception information.Conclusions. HIV-infected men and women with serodiscordant partners are receptive to the idea of safer conception counseling. HCWs need to be supported to routinely initiate accurate safer conception counseling with HIV-infected patients of reproductive age.

scholarly journals The cost effectiveness and optimal configuration of HIV self-test distribution in South Africa: a model analysis

2021 ◽  
Vol 6 (Suppl 4) ◽  
pp. e005598
Author(s):  
Lise Jamieson ◽  
Leigh F Johnson ◽  
Katleho Matsimela ◽  
Linda Alinafe Sande ◽  
Marc d'Elbée ◽  
...  
Keyword(s):  
South Africa ◽  
Cost Effectiveness ◽  
Scale Up ◽  
Cost Effective ◽  
Health Impact ◽  
Status Quo ◽  
Fractional Factorial ◽  
Self Testing ◽  
Life Years ◽  
The Impact

BackgroundHIV self-testing (HIVST) has been shown to be acceptable, feasible and effective in increasing HIV testing uptake. Novel testing strategies are critical to achieving the UNAIDS target of 95% HIV-positive diagnosis by 2025 in South Africa and globally.MethodsWe modelled the impact of six HIVST kit distribution modalities (community fixed-point, taxi ranks, workplace, partners of primary healthcare (PHC) antiretroviral therapy (ART) patients), partners of pregnant women, primary PHC distribution) in South Africa over 20 years (2020–2039), using data collected alongside the Self-Testing AfRica Initiative. We modelled two annual distribution scenarios: (A) 1 million HIVST kits (current) or (B) up to 6.7 million kits. Incremental economic costs (2019 US$) were estimated from the provider perspective; assumptions on uptake and screening positivity were based on surveys of a subset of kit recipients and modelled using the Thembisa model. Cost-effectiveness of each distribution modality compared with the status-quo distribution configuration was estimated as cost per life year saved (estimated from life years lost due to AIDS) and optimised using a fractional factorial design.ResultsThe largest impact resulted from secondary HIVST distribution to partners of ART patients at PHC (life years saved (LYS): 119 000 (scenario A); 393 000 (scenario B)). However, it was one of the least cost-effective modalities (A: $1394/LYS; B: $4162/LYS). Workplace distribution was cost-saving ($52–$76 million) and predicted to have a moderate epidemic impact (A: 40 000 LYS; B: 156 000 LYS). An optimised scale-up to 6.7 million tests would result in an almost threefold increase in LYS compared with a scale-up of status-quo distribution (216 000 vs 75 000 LYS).ConclusionOptimisation-informed distribution has the potential to vastly improve the impact of HIVST. Using this approach, HIVST can play a key role in improving the long-term health impact of investment in HIVST.

scholarly journals The impact of the timely birth dose vaccine on the global elimination of hepatitis B

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Margaret J. de Villiers ◽  
Shevanthi Nayagam ◽  
Timothy B. Hallett
Keyword(s):  
Hepatitis B ◽  
Horizontal Transmission ◽  
Scale Up ◽  
Scaling Up ◽  
World Health ◽  
Birth Cohorts ◽  
Middle Income ◽  
Hbv Vaccine ◽  
Birth Dose ◽  
The Impact

AbstractIn 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.

scholarly journals An evolutionary-based approach to quantify the genetic barrier to drug resistance in fast-evolving viruses: an application to HIV-1 subtypes and integrase inhibitors

2019 ◽  
Author(s):  
Kristof Theys ◽  
Pieter Libin ◽  
Kristel Van Laethem ◽  
Ana B Abecasis
Keyword(s):  
Drug Resistance ◽  
Antiviral Treatment ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Genetic Barrier ◽  
Viral Pathogens ◽  
Subtype B ◽  
Genetic Potential ◽  
The Impact ◽  
Hiv 1

AbstractViral pathogens causing global disease burdens are often characterised by high rates of evolutionary changes, facilitating escape from therapeutic or immune selective pressure. Extensive viral diversity at baseline can shorten the time to resistance emergence and alter mutational pathways, but the impact of genotypic background on the genetic barrier can be difficult to capture, in particular for antivirals in experimental stages, recently approved or expanded into new settings. We developed an evolutionary-based counting method to quantify the population genetic potential to resistance and assess differences between populations. We demonstrate its applicability to HIV-1 integrase inhibitors, as their increasing use globally contrasts with limited availability of non-B subtype resistant sequences and corresponding knowledge gap on drug resistance. A large sequence dataset encompassing most prevailing subtypes and resistance mutations of first- and second-generation inhibitors were investigated. A varying genetic potential for resistance across HIV-1 subtypes was detected for 15 mutations at 12 positions, with notably 140S in subtype B, while 140C was discarded to vary across subtypes. An additional analysis for HIV-1 reverse transcriptase inhibitors identified a higher potential for 65R in subtype C, on the basis of a differential codon usage not reported before. The evolutionary interpretation of genomic differences for antiviral treatment remains challenging. Our framework advances existing counting methods with an increased sensitivity that identified novel subtype dependencies as well as rejected previous statements. Future applications include novel HIV-1 drug classes as well as other viral pathogens.

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