Neighbourhood risk factors of recurrent tuberculosis in Cape Town: a cohort study using geocoded notification data.

BACKGROUND: Individuals with a history of tuberculosis (TB) disease are at higher risk of developing a subsequent episode than those without. Considering the role of social and environmental factors in tuberculosis, we assessed neighbourhood-level risk factors associated with recurrent tuberculosis in Cape Town, South Africa. METHODS: This cohort consisted of patients who completed treatment for their first drug-sensitive TB episode between 2003 and 2015. Addresses were geocoded at neighbourhood level. Data on neighbourhood-level factors were obtained from the Census 2011 (household size, population density) and the City of Cape Town (Socio-Economic Index). Neighbourhood-level TB burden was calculated annually by dividing the number of notified TB episodes by the population in that neighbourhood. Multilevel survival analysis was performed with the outcome recurrent TB, defined as a second episode of TB, and controlling for individual-level risk factors (age, gender and time since first episode in years). Follow-up ended at the second episode, or on 31 December 2015, whichever came first. RESULTS: The study included 173 421 patients from 700 neighbourhoods. Higher Socio-Economic Index was associated with a lower risk of recurrence compared with average Socio-Economic Index. An increased risk was found for higher household size and TB burden, with an increase of 20% for every additional person in mean household size and 10% for every additional TB episode/100 inhabitants. No association was found with population density. CONCLUSION: Recurrent TB was associated with increased household size and TB burden at neighbourhood level. These findings could be used to target TB screening activities.

Health systems and health equity: Advancing the agenda.

Despite a compelling body of evidence and decades of policy recommendations, deep inequities in health persist with historically marginalized groups. Operationalizing strategies to achieve equity in health and health care continues to remain elusive to health systems. We propose several focus areas; attention to semantics and concepts, building knowledge of health inequities, redesigning care and transforming cultures, to advance health equity work by health system nurse leaders and clinical nurses. Health equity frameworks, traditionally applied in population and public health, are also discussed to tackle health equity issues and formulate, implement and evaluate solutions to inequities. Examples illustrate ongoing work in our health system in targeted areas and challenges in advancing health equity work. Future efforts by health system nurse leaders should concentrate on technology for point of care health screening and data acquisition, data-driven decisions, and organizational performance measures to narrow health equity gaps.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Cost-effectiveness of a Novel Lipoarabinomannan Test for Tuberculosis in Patients With Human Immunodeficiency Virus.

BACKGROUND: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with human immunodeficiency virus (HIV), irrespective of symptoms. METHODS: We used a microsimulation model to project clinical and economic outcomes of 3 testing strategies: (1) sputum Xpert MTB/RIF (Xpert), (2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM), (3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modeled cohort matched that of a 2-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4 <200 cells/µL: 33%/62%/70%; among those with CD4 ≥200 cells/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were US$15/3/6 (South Africa) and $25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (US$/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide. RESULTS: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to 5-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors. CONCLUSIONS: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study.

BACKGROUND: Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa. METHODS: We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. FINDINGS: When Re was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When Re was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which Re was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced. INTERPRETATION: In South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations. FUNDING: US National Institutes of Health, Royal Society, Wellcome Trust.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study.

BACKGROUND: Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. METHODS: We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and molecular testing for symptomatic individuals (MS); and Quarantine Centres (QC), for household contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (Re) of 1·5 and 1·2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER)

Shortened Tuberculosis Treatment for People with HIV in South Africa. A Model-based Evaluation and Cost-effectiveness Analysis.

Rationale: Recent tuberculosis treatment trials failed to show that some 4-month (4m) regimens were noninferior to conventional 6-month (6m) regimens for a composite clinical outcome. Novel shortened regimens may still have important clinical and economic benefits in populations with high loss to follow-up (LTFU) and in subgroups such as people with human immunodeficiency virus.Objectives: To identify scenarios in which a novel 4m regimen would be preferred to a conventional 6m regimen for treatment of drug-susceptible tuberculosis in people with human immunodeficiency virus in South Africa, in terms of short-term and long-term clinical and economic outcomes.Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to project outcomes modeled on participants in the OFLOTUB trial. For calibration purposes, we did a base case analysis by applying trial-informed parameters for the 4m/6m regimens, including monthly LTFU during treatment (0.68%/0.83%), average monthly tuberculosis recurrence (0.65%/0.31%), and monthly drug costs (U.S. dollars [USD]25.90/3.70). We then evaluated different scenarios and 4m regimen characteristics, varying key parameters, including LTFU (informed by observational cohort data), recurrence, and cost. We projected outcomes, including 2-year mortality and life expectancy. We conducted a cost-effectiveness analysis, evaluating the incremental cost-effectiveness ratio of a 4m versus 6m regimen.Results: In the base case model analysis, risk of the composite unfavorable outcome in the 4m/6m groups was 19.8%/15.9%, similar to the trial; projected life expectancies were 22.1/22.3 years. In analyses of alternative scenarios and 4m regimen characteristics, a 4m regimen yielded lower risk of the composite unfavorable outcome than the conventional 6m regimen if LTFU increased to greater than 3.5%/mo or if average recurrence after a 4m regimen decreased to less than 0.45%/mo, and it yielded higher life expectancy if LTFU was greater than 3.5%/mo or if recurrence was less than 0.5%/mo. A 4m regimen was not cost-effective in the base case but became cost-effective (incremental cost-effectiveness ratio

The differential impact of HIV and antiretroviral therapy on gender-specific tuberculosis rates.

OBJECTIVE: To assess the impact of the HIV epidemic and the rollout of antiretroviral therapy (ART) from 2004 on the gender-specific TB burden in Cape Town, we investigated temporal changes in TB notification rates, the HIV-associated relative risk of TB and the population attributable risk fraction (PAF) of HIV by gender. METHODS: Annual TB notifications, mid-year population and HIV prevalence estimates were used to calculate rates per 100 000 population stratified by gender and HIV. Annual rate ratios (RR) of TB associated with HIV and PAF were calculated by gender. RESULTS: Pre-HIV TB notification rates were lower among women than men (146/100 000 vs. 247/100 000). With the onset of the HIV, epidemic rates increased 5.3-fold in women (to 778/100 000) and 3.7-fold in men (to 917/100 000) to a peak in 2008, after which they declined by 25% in women (to 634/100 000) and 18% in men (to 755/100 000) by 2014. The HIV-associated RR of TB was 25% higher in women than in men in 2006 (25 vs. 20), but decreased to the same level in 2014. HIV PAF declined between 2008 and 2014 from 56% to 50% and from 40% to 38% in women and men, respectively. CONCLUSIONS: The HIV epidemic led to greater relative increases in TB rates among women than men. The increased HIV-associated TB risk in women could be compatible with removal of the biological protection of female gender by HIV infection. The decline in RR and PAF in HIV-positive women could be explained by increasing ART usage reversing female gender-related susceptibility.

OBJECTIF: Afin d'évaluer l'impact de l'épidémie du VIH et le déploiement du traitement antirétroviral (ART depuis 2004) sur la charge de la tuberculose (TB) spécifique au sexe, à Cape Town, nous avons examiné les changements temporels dans les taux de notification de la TB, le risque relatif de TB associé au VIH et la fraction de risque attribuable à la population (FAP) du VIH par sexe. MÉTHODES: Les notifications annuelles de la TB, les estimations de la population en milieu d'année et de la prévalence du VIH ont été utilisées pour calculer les taux par 100.000 habitants stratifiés par sexe et VIH. Les rapports de risque (RR) annuels de TB associé au VIH et la FAP ont été calculés par sexe. RÉSULTATS: Les taux de notification de la TB avant le VIH étaient plus faibles chez les femmes que chez les hommes (146 sur 100.000 contre 247 sur 100.000). Avec le début de l'épidémie de VIH, les taux ont augmenté de 5,3 fois chez les femmes (à 778/100.000) et de 3,7 fois chez les hommes (à 917/100.000) pour atteindre un pic en 2008. Puis, ils ont diminué de 25% chez les femmes (à 634/100.000) et de 18% chez les hommes (à 755/100.000) en 2014. Les RR de TB associés au VIH étaient 25% plus élevés chez les femmes que chez les hommes en 2006 (25 contre 20), mais ont diminué au même niveau en 2014. La FAP du VIH a diminué entre 2008 et 2014, passant de 56% à 50% et de 40% à 38% chez les femmes et les hommes, respectivement. CONCLUSIONS: L'épidémie du VIH a entraîné une augmentation relative du taux de TB chez les femmes supérieure à celle des hommes. L'augmentation du risque de TB associé au VIH chez les femmes pourrait être compatible avec la suppression de la protection biologique du sexe féminin par l'infection au VIH. La baisse des RR et de la FAP chez les femmes VIH positives pourrait être expliquée par une augmentation de l'utilisation de l'ART inversant la sensibilité liée au sexe féminin.

Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.

BACKGROUND: Testing urine improves the number of tuberculosis diagnoses made among patients in hospital with HIV. In conjunction with the two-country randomised Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa (STAMP) trial, we used a microsimulation model to estimate the effects on clinical outcomes and the cost-effectiveness of adding urine-based tuberculosis screening to sputum screening for hospitalised patients with HIV. METHODS: We compared two tuberculosis screening strategies used irrespective of symptoms among hospitalised patients with HIV in Malawi and South Africa: a GeneXpert assay (Cepheid, Sunnyvale, CA, USA) for Mycobacterium tuberculosis and rifampicin resistance (Xpert) in sputum samples (standard of care) versus sputum Xpert combined with a lateral flow assay for M tuberculosis lipoarabinomannan in urine (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [formerly Alere]; TB-LAM) and concentrated urine Xpert (intervention). A cohort of simulated patients was modelled using selected characteristics of participants, tuberculosis diagnostic yields, and use of hospital resources in the STAMP trial. We calibrated 2-month model outputs to the STAMP trial results and projected clinical and economic outcomes at 2 years, 5 years, and over a lifetime. We judged the intervention to be cost-effective if the incremental cost-effectiveness ratio (ICER) was less than US$750/year of life saved (YLS) in Malawi and $940/YLS in South Africa. A modified intervention of adding only TB-LAM to the standard of care was also evaluated. We did a budget impact analysis of countrywide implementation of the intervention. FINDINGS: The intervention increased life expectancy by 0·5-1·2 years and was cost-effective, with an ICER of $450/YLS in Malawi and $840/YLS in South Africa. The ICERs decreased over time. At lifetime horizon, the intervention remained cost-effective under nearly all modelled assumptions. The modified intervention was at least as cost-effective as the intervention (ICERs $420/YLS in Malawi and $810/YLS in South Africa). Over 5 years, the intervention would save around 51 000 years of life in Malawi and around 171 000 years of life in South Africa. Health-care expenditure for screened individuals was estimated to increase by $37 million (10·8%) and $261 million (2·8%), respectively. INTERPRETATION: Urine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in resource-limited settings. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert, making a compelling case for expanding its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis. FUNDING: UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital.

Environmental and social factors impacting on epidemic and endemic tuberculosis: a modelling analysis.

Tuberculosis (TB) transmission results from the interaction between infective sources and susceptible individuals within enabling socio-environmental conditions. As TB is an airborne pathogen, the transmission probability is determined by the volume of air inhaled from an infected source and the concentration of Mycobacterium tuberculosis containing respirable particles (doses) per volume of air. In this study, we model the contributions of infectious dose production, prevalence of infectious cases and daily rebreathed air volume (RAV) for defining the boundary conditions necessary to sustain endemic TB transmission at the population level. Results suggest that in areas with high RAV (range 300-1000 l d-1), such as prisons, TB transmission is contributed by both super-spreaders (exhaling ≥10 infectious doses hr-1) and lower infectivity individuals (exhaling less than 10 infectious doses hr-1). In settings with a low quantity of RAV (less than 100 l d-1), TB transmission occurs only from super-spreaders. Point-source epidemics occur in low rebreathed environments when super-spreaders infect a number of susceptibles but subsequent transmission is limited by the mean infectivity of secondary cases. By contrast, endemic TB occurs in poor socio-environmental conditions where mean infectivity cases are able to maintain a sufficiently high effective contact number.

The value of point-of-care CD4+ and laboratory viral load in tailoring antiretroviral therapy monitoring strategies to resource limitations.

OBJECTIVE: To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. DESIGN/METHODS: We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. RESULTS: In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). CONCLUSION: In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.

Do Less Harm: Evaluating HIV Programmatic Alternatives in Response to Cutbacks in Foreign Aid.

BACKGROUND: Resource-limited nations must consider their response to potential contractions in international support for HIV programs. OBJECTIVE: To evaluate the clinical, epidemiologic, and budgetary consequences of alternative HIV program scale-back strategies in 2 recipient nations, the Republic of South Africa (RSA) and Côte d'Ivoire (CI). DESIGN: Model-based comparison between current standard (CD4 count at presentation of 0.260 × 109 cells/L, universal antiretroviral therapy [ART] eligibility, and 5-year retention rate of 84%) and scale-back alternatives, including reduced HIV detection, no ART or delayed initiation (when CD4 count is <0.350 × 109 cells/L), reduced investment in retention, and no viral load monitoring or second-line ART. DATA SOURCES: Published RSA- and CI-specific estimates of the HIV care continuum, ART efficacy, and HIV-related costs. TARGET POPULATION: HIV-infected persons, including future incident cases. TIME HORIZON: 5 and 10 years. PERSPECTIVE: Modified societal perspective, excluding time and productivity costs. OUTCOME MEASURES: HIV transmissions and deaths, years of life, and budgetary outlays (2015 U.S. dollars). RESULTS OF BASE-CASE ANALYSIS: At 10 years, scale-back strategies increase projected HIV transmissions by 0.5% to 19.4% and deaths by 0.6% to 39.1%. Strategies can produce budgetary savings of up to 30% but no more. Compared with the current standard, nearly every scale-back strategy produces proportionally more HIV deaths (and transmissions, in RSA) than savings. When the least harmful and most efficient alternatives for achieving budget cuts of 10% to 20% are applied, every year of life lost will save roughly $900 in HIV-related outlays in RSA and $600 to $900 in CI. RESULTS OF SENSITIVITY ANALYSIS: Scale-back programs, when combined, may result in clinical and budgetary synergies and offsets. LIMITATION: The magnitude and details of budget cuts are not yet known, nor is the degree to which other international partners might step in to restore budget shortfalls. CONCLUSION: Scaling back international aid to HIV programs will have severe adverse clinical consequences; for similar economic savings, certain programmatic scale-back choices result in less harm than others. PRIMARY FUNDING SOURCE: National Institutes of Health and Steve and Deborah Gorlin MGH Research Scholars Award.

Setting Performance Standards for a Cost-Effective Human Immunodeficiency Virus Cure Strategy in South Africa.

BACKGROUND: Reports of a single case of human immunodeficiency virus (HIV) eradication suggest that elimination of HIV from individuals is possible. Anticipating both increased research funding and the development of effective, durable cure technologies, we describe the circumstances under which a cure might improve survival and be cost-effective in South Africa. METHODS: We adapted a simulation model comparing a hypothetical cure strategy ("Cure") to the standard of care, lifetime antiretroviral therapy ("LifetimeART") among adherent South Africans (58% female; mean age 33.8 years; mean CD4 257/µL; virologic suppression ≥1 year). We portrayed cure as a single intervention, producing sustained viral eradication without ART. We considered both a plausible, more imminently achievable "Baseline Scenario" and a more aspirational "Optimistic Scenario". Inputs (Baseline/Optimistic) included the following: 50%/75% efficacy; 0.6%/0.0% fatal toxicity; 0.37%/0.085% monthly relapse over 5 years (0.185%/0.0425% per month thereafter); and $2000/$500 cost. These inputs were varied extensively in sensitivity analysis. RESULTS: At baseline, Cure was "dominated," yielding lower discounted life expectancy (19.31 life-years [LY] vs 19.37 LY) and greater discounted lifetime costs ($13 800 vs $13 700) than LifetimeART. Under optimistic assumptions, Cure was "cost-saving," producing greater survival (19.91 LY) and lower lifetime costs ($11 000) than LifetimeART. Findings were highly sensitive to data assumptions, leaving little middle ground where a tradeoff existed between improved survival and higher costs. CONCLUSIONS: Only under the most favorable performance assumptions will an HIV cure strategy prove clinically and economically justifiable in South Africa. The scientific pursuit of a cure should not undermine continued expansions of access to proven, effective, and cost-effective ART.

The Anticipated Clinical and Economic Effects of 90-90-90 in South Africa.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 global treatment target aims to achieve 73% virologic suppression among HIV-infected persons worldwide by 2020. OBJECTIVE: To estimate the clinical and economic value of reaching this ambitious goal in South Africa, by using a microsimulation model of HIV detection, disease, and treatment. DESIGN: Modeling of the "current pace" strategy, which simulates existing scale-up efforts and gradual increases in overall virologic suppression from 24% to 36% in 5 years, and the UNAIDS target strategy, which simulates 73% virologic suppression in 5 years. DATA SOURCES: Published estimates and South African survey data on HIV transmission rates (0.16 to 9.03 per 100 person-years), HIV-specific age-stratified fertility rates (1.0 to 9.1 per 100 person-years), and costs of care ($11 to $31 per month for antiretroviral therapy and $20 to $157 per month for routine care). TARGET POPULATION: South African HIV-infected population, including incident infections over the next 10 years. PERSPECTIVE: Modified societal perspective, excluding time and productivity costs. TIME HORIZON: 5 and 10 years. INTERVENTION: Aggressive HIV case detection, efficient linkage to care, rapid treatment scale-up, and adherence and retention interventions toward the UNAIDS target strategy. OUTCOME MEASURES: HIV transmissions, deaths, years of life saved, maternal orphans, costs (2014 U.S. dollars), and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Compared with the current pace strategy, over 5 years the UNAIDS target strategy would avert 873 000 HIV transmissions, 1 174 000 deaths, and 726 000 maternal orphans while saving 3 002 000 life-years; over 10 years, it would avert 2 051 000 HIV transmissions, 2 478 000 deaths, and 1 689 000 maternal orphans while saving 13 340 000 life-years. The additional budget required for the UNAIDS target strategy would be $7.965 billion over 5 years and $15.979 billion over 10 years, yielding an incremental cost-effectiveness ratio of $2720 and $1260 per year of life saved, respectively. RESULTS OF SENSITIVITY ANALYSIS: Outcomes generally varied less than 20% from base-case outcomes when key input parameters were varied within plausible ranges. LIMITATION: Several pathways may lead to 73% overall virologic suppression; these were examined in sensitivity analyses. CONCLUSION: Reaching the 90-90-90 HIV suppression target would be costly but very effective and cost-effective in South Africa. Global health policymakers should mobilize the political and economic support to realize this target. PRIMARY FUNDING SOURCE: National Institutes of Health and the Steve and Deborah Gorlin MGH Research Scholars Award.

Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection.

BACKGROUND: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. METHODS: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. RESULTS: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. CONCLUSIONS: Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives.

Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

BACKGROUND: HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS: We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS: In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS: CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.

Point-of-care CD4 testing to inform selection of antiretroviral medications in south african antenatal clinics: a cost-effectiveness analysis.

BACKGROUND: Many prevention of mother-to-child HIV transmission (PMTCT) programs currently prioritize antiretroviral therapy (ART) for women with advanced HIV. Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART instead of zidovudine, but are costlier than traditional laboratory assays. METHODS: We used validated models of HIV infection to simulate pregnant, HIV-infected women (mean age 26 years, gestational age 26 weeks) in a general antenatal clinic in South Africa, and their infants. We examined two strategies for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost: $26). We modeled South African PMTCT guidelines during the study period (WHO "Option A"): antenatal zidovudine (CD4 ≤350/µL) or ART (CD4>350/µL). Outcomes included MTCT risk at weaning (age 6 months), maternal and pediatric life expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and cost-effectiveness ($/life-year saved). RESULTS: In the base case, laboratory led to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person). Compared to laboratory, POC improved clinical outcomes and reduced healthcare costs. CONCLUSIONS: In antenatal clinics implementing Option A, the higher initial cost of a one-time POC CD4 assay will be offset by cost-savings from prevention of pediatric HIV infection.

Provision of antiretroviral therapy in South Africa: the nuts and bolts.

Public sector antiretroviral provision had a slow start in South Africa despite a raging epidemic and a World AIDS conference that shed significant public light on the disparities of therapy access globally. This was largely due to political prevarication in the midst of AIDS denialism. There has been an unprecedented expansion in the HIV treatment programme since 2008. As a result, South Africa now has the largest number of patients on antiretroviral drugs in the world, and South African life expectancy has increased by more than a decade. However, this has led to a number of fiscal, logistic and operational challenges that the country must face as the treatment programme continues to expand. Challenges include increasing detection within communities, linkage and retention in care, while strengthening operational support functions such as consistent drug supply, health staffing and infrastructure, diagnostic services, programme monitoring and sustainable financing. As a middle-income country, albeit with marked income inequality, and the heaviest HIV burden in the world, South Africa is a test case of whether a large-scale public health programme can boast of success in the face of numerous other health-system challenges.

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

BACKGROUND: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. METHODS AND FINDINGS: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. CONCLUSIONS: POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.

Mobile HIV screening in Cape Town, South Africa: clinical impact, cost and cost-effectiveness.

BACKGROUND: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. METHODS AND FINDINGS: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%-58%, females 49%-58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and $31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be "very cost-effective" when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was $2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. CONCLUSION: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority.