Systematic review and meta-analysis of community and facility-based HIV testing to address linkage to care gaps in sub-Saharan Africa.

HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing modalities, characterizing community (home, mobile, index, key populations, campaign, workplace and self-testing) and facility approaches by population reached, HIV positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing and counselling had high coverage and uptake and identified HIV-positive people at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% confidence interval (CI) = 47-54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65-67%). Few studies evaluated HIV testing for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19-62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63-88%), indicating service gaps. Community testing with facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87-98%) and antiretroviral initiation (75%, 95% CI = 68-82%). Expanding home and mobile testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention, and decrease HIV burden.

Spatial distribution and characteristics of HIV clusters in Ethiopia.

OBJECTIVES: Ethiopia's HIV prevalence has decreased by 75% in the past 20 years with the implementation of antiretroviral therapy, but HIV transmission continues in high-risk clusters. Identifying the spatial and temporal trends, and epidemiologic correlates, of these clusters can lead to targeted interventions. METHODS: We used biomarker and survey data from the 2005, 2011 and 2016 Ethiopia Demographic and Health Surveys (DHS). The spatial-temporal distribution of HIV was estimated using the Kulldorff spatial scan statistic, a likelihood-based method for determining clustering. Significant clusters (P < 0.05) were identified and compared based on HIV risk factors to non-cluster areas. RESULTS: In 2005, 2011 and 2016, respectively, 219, 568 and 408 individuals tested positive for HIV. Four HIV clusters were identified, representing 17% of the total population and 43% of all HIV cases. The clusters were centred around Addis Ababa (1), Afar (2), Dire Dawa (3) and Gambella (4). Cluster 1 had higher rates of unsafe injections (4.9% vs. 2.2%, P < 0.001) and transactional sex (6.0% vs. 1.6%, P < 0.001) than non-cluster regions, but more male circumcision (98.5% vs. 91.3%, P < 0.001). Cluster 2 had higher levels of transactional sex (4.9% vs. 1.6%, P < 0.01), but lower levels of unsafe injections (0.8% vs. 2.2%, P < 0.01). Cluster 3 had fewer individuals with> 1 sexual partner (0% vs. 1.7%, P < 0.001) and more male circumcision (100% vs. 91.3%, P < 0.001). Cluster 4 had less male circumcision (59.1% vs. 91.3%, P < 0.01). CONCLUSIONS: In Ethiopia, geographic HIV clusters are driven by different risk factors. Decreasing the HIV burden requires targeted interventions.

OBJECTIFS: La prévalence du VIH en Ethiopie a diminué de 75% au cours des 20 dernières années avec l'implémentation du traitement antirétroviral, mais la transmission du VIH se poursuit dans les grappes à haut risque. L'identification des tendances spatiales et temporelles et des corrélations épidémiologiques de ces grappes peut mener à des interventions ciblées. MÉTHODES: Nous avons utilisé des biomarqueurs et des données d'enquête provenant des Surveillances Démographiques et de Santé (SDS) en Ethiopie de 2005, 2011 et 2016. La distribution spatiotemporelle du VIH a été estimée à l'aide de la statistique de balayage spatial de Kulldorff, une méthode basée sur la probabilité de déterminer des regroupements. Des grappes significatives (P < 0.05) ont été identifiées et comparées sur base des facteurs de risque du VIH dans les zones sans regroupements. RÉSULTATS: En 2005, 2011 et 2016, respectivement, 219, 568 et 408 personnes ont été testées positives pour le VIH. Quatre grappes de VIH ont été identifiées, représentant 17% de la population totale et 43% de tous les cas de VIH. Les grappes étaient centrées sur Addis-Abeba (1), Afar (2), Dire Dawa (3) et Gambella(4). La grappe 1 avait des taux plus élevés d'injections à risque (4,9% contre 2,2%, P < 0.001) et de rapports sexuels transactionnels (6,0% contre 1,6%, P < 0.001) que les régions sans regroupement, mais plus de circoncisions masculines (98,5% contre 91,3%, p <0,001). La grappe 2 avait des taux plus élevés de rapports sexuels transactionnels (4,9% contre 1,6%, P < 0.01), mais des taux inférieurs d'injections à risque (0,8% contre 2,2%, P < 0.01). La grappe 3 avait moins d'individus avec >1 partenaire sexuel (0% contre 1,7%, P < 0.001) et plus de circoncisions masculines (100% contre 91,3%, P < 0.001). La grappe 4 avait moins de circoncisions masculines (59,1% contre 91,3%, P < 0.01). CONCLUSIONS: En Ethiopie, les grappes géographiques du VIH sont guidées par différents facteurs de risque. La réduction de la charge du VIH nécessite des interventions ciblées.

CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility.

Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation.

Modeling the implementation of universal coverage for HIV treatment as prevention and its impact on the HIV epidemic.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) recently updated its global targets for antiretroviral therapy (ART) coverage for HIV-positive persons under which 90 % of HIV-positive people are tested, 90 % of those are on ART, and 90 % of those achieve viral suppression. Treatment policy is moving toward treating all HIV-infected persons regardless of CD4 cell count-otherwise known as treatment as prevention-in order to realize the full therapeutic and preventive benefits of ART. Mathematical models have played an important role in guiding the development of these policies by projecting long-term health impacts and cost-effectiveness. To guide future policy, new mathematical models must consider the barriers patients face in receiving and taking ART. Here, we describe the HIV care cascade and ART delivery supply chain to examine how mathematical modeling can provide insight into cost-effective strategies for scaling-up ART coverage in sub-Saharan Africa and help achieve universal ART coverage.

Population health impact, cost-effectiveness, and affordability of community-based HIV treatment and monitoring in South Africa: A health economics modelling study.

Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy. We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. Using a health system perspective, we evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. In a sensitivity analysis, we varied the discount rate; time horizon; costs for clinic and community ART, hospitalisation, and testing; and the proportion of the population receiving community ART. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3-31.5) of incident HIV infections, 27.8% (26.8-28.8) of HIV-related deaths, and 18.7% (17.9-19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15-24 years experienced the greatest reduction in incident HIV (30.7%, 27.1-34.7). In the first five years (2020-2024), community ART required an additional $44.9 million (35.8-50.1) annually, representing 14.3% (11.4-16.0) of the annual HIV budget. The cost per DALY averted was $102 (85-117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9-92.8). Cost-effectiveness was robust to sensitivity analyses. In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.

Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs.

INTRODUCTION: Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated. METHODS: We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/µL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. RESULTS: The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200cells/µL was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4≤500cells/µL, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of $2822 and $812 per HIV infection averted and QALY gained, respectively. CONCLUSION: Even when compared with valacyclovir suppression, a drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment would most effectively and efficiently reduce the HIV burden.

Assisted partner notification services are cost-effective for decreasing HIV burden in western Kenya.

BACKGROUND: Assisted partner services (aPS) or provider notification for sexual partners of persons diagnosed HIV positive can increase HIV testing and linkage in Sub-Saharan Africa and is a high yield strategy to identify HIV-positive persons. However, its cost-effectiveness is not well evaluated. METHODS: Using effectiveness and cost data from an aPS trial in Kenya, we parameterized an individual-based, dynamic HIV transmission model. We estimated costs for both a program scenario and a task-shifting scenario using community health workers to conduct the intervention. We simulated 200 cohorts of 500 000 individuals and projected the health and economic effects of scaling up aPS in a region of western Kenya (formerly Nyanza Province). FINDINGS: Over a 10-year time horizon with universal antiretroviral therapy (ART) initiation, implementing aPS in western Kenya was projected to reach 12.5% of the population and reduce incident HIV infections by 3.7%. In sexual partners receiving aPS, HIV-related deaths were reduced by 13.7%. The incremental cost-effectiveness ratio of aPS was $1094 (US dollars) (90% model variability $823-1619) and $833 (90% model variability $628-1224) per disability-adjusted life year averted under the program and task-shifting scenario, respectively. The incremental cost-effectiveness ratios for both scenarios fall below Kenya's gross domestic product per capita ($1358) and are therefore considered very cost-effective. Results were robust to varying healthcare costs, linkage to care rates, partner concurrency rates, and ART eligibility thresholds (≤350 cells/µl, ≤500 cells/µl, and universal ART). INTERPRETATION: APS is cost-effective for reducing HIV-related morbidity and mortality in western Kenya and similar settings. Task shifting can increase program affordability.

Modeling the Cost-Effectiveness of Home-Based HIV Testing and Education (HOPE) for Pregnant Women and Their Male Partners in Nyanza Province, Kenya.

INTRODUCTION: Women in sub-Saharan Africa face a 2-fold higher risk of HIV acquisition during pregnancy and postpartum and the majority do not know the HIV status of their male partner. Home-based couple HIV testing for pregnant women can reduce HIV transmission to women and infants while increasing antiretroviral therapy (ART) coverage in men. However, the cost-effectiveness of this program has not been evaluated. METHODS: We modeled the health and economic impact of implementing a home-based partner education and HIV testing (HOPE) intervention for pregnant women and their male partners in a region of Western Kenya (formally Nyanza Province). We used data from the HOPE randomized clinical trial conducted in Kisumu, Kenya, to parameterize a mathematical model of HIV transmission. We conducted an in-country microcosting of the HOPE intervention (payer perspective) to estimate program costs as well as a lower cost scenario of task-shifting to community health workers. RESULTS: The incremental cost of adding the HOPE intervention to standard antenatal care was $31-37 and $14-16 USD per couple tested with program and task-shifting costs, respectively. At 60% coverage of male partners, HOPE was projected to avert 6987 HIV infections and 2603 deaths in Nyanza province over 10 years with an incremental cost-effectiveness ratio (ICER) of $886 and $615 per disability-adjusted life year averted for the program and task-shifting scenario, respectively. ICERs were robust to changes in intervention coverage, effectiveness, and ART initiation and dropout rates. CONCLUSIONS: The HOPE intervention can moderately decrease HIV-associated morbidity and mortality by increasing ART coverage in male partners of pregnant women. ICERs fall below Kenya's per capita gross domestic product ($1358) and are therefore considered cost-effective. Task-shifting to community health workers can increase intervention affordability and feasibility.

Home testing and counselling to reduce HIV incidence in a generalised epidemic setting: a mathematical modelling analysis.

BACKGROUND: Home HIV testing and counselling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, might facilitate expansion of antiretroviral therapy (ART) coverage. We used a mathematical model to assess the effect of periodic home HTC programmes on HIV incidence in KwaZulu-Natal, South Africa. METHODS: We developed a dynamic HIV transmission model with parameters, primary cost data, and measures of viral suppression collected from a prospective study of home HTC in KwaZulu-Natal. In our model, we assumed home HTC took place every 5 years with ART initiation for people with CD4 counts of 350 cells per µL or less. For individuals with CD4 counts of more than 350 cells per µL, we compared increasing ART coverage for those with 350-500 cells per µL with initiating treatment for those who have viral loads of more than 10 000 copies per mL. FINDINGS: Maintaining the presently observed level of 36% viral suppression in HIV-positive people, HIV incidence decreases by 33·8% over 10 years. Home HTC every 5 years with linkage to care with ART initiation at CD4 counts of 350 cells per µL or less reduces HIV incidence by 40·6% over 10 years. Expansion of ART to people with CD4 counts of more than 350 cells per µL who also have a viral load of 10 000 copies per mL or more decreases HIV incidence by 51·6%, and this was the most cost-effective strategy for prevention of HIV infections at US$2960 per infection averted. Expansion of ART eligibility CD4 counts of 350-500 cells per µL is cost-effective at $900 per quality-adjusted life-year gained. Following health economic guidelines, expansion of ART use to individuals who have viral loads of more than 10 000 copies per mL among those with CD4 counts of more than 350 cells per µL was cost-effective to reduce HIV-related morbidity. INTERPRETATION: Our results show that province-wide home HTC every 5 years can be a cost-effective strategy to increase ART coverage and reduce HIV burden. Expanded ART initiation criteria that includes individuals with high viral load will improve the effectiveness of home HTC in linking individuals to ART who are at high risk of transmitting HIV, thereby preventing morbidity and onward transmission. FUNDING: National Institutes of Health.

Cost-effectiveness of pre-exposure prophylaxis targeted to high-risk serodiscordant couples as a bridge to sustained ART use in Kampala, Uganda.

INTRODUCTION: Despite scale-up of antiretroviral therapy (ART) for treating HIV-positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV-negative persons as pre-exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost-effectiveness of implementing time-limited PrEP as a short-term bridge during the first six months of ART for the HIV-positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy-makers considering PrEP implementation. METHODS: To estimate the real world delivery costs of PrEP, we conducted micro-costing and time and motion analyses in an open-label prospective study of PrEP and ART delivery targeted to high-risk serodiscordant couples in Uganda (the Partners Demonstration Project). The cost (in USD, in 2012) of PrEP and ART for serodiscordant couples was assessed, with and without research components, in the study setting. Using Ministry of Health costs, the cost of PrEP and ART provision within a government programme was estimated, as was the cost of providing PrEP in addition to ART. We parameterized an HIV transmission model to estimate the health and economic impacts of 1) PrEP and ART targeted to high-risk serodiscordant couples in the context of current ART use and 2) increasing ART coverage to 55% of HIV-positive persons with CD4 ≤500 cells/µL without PrEP. The incremental cost-effectiveness ratios (ICERs) per HIV infection and disability-adjusted life year (DALY) averted were calculated over 10 years. RESULTS: The annual cost of PrEP and ART delivery for serodiscordant couples was $1058 per couple in the study setting and $453 in the government setting. The portion of the programme cost due to PrEP was $408 and $92 per couple per year in the study and government settings, respectively. Over 10 years, a programme of PrEP and ART for high-risk serodiscordant couples was projected to avert 43% of HIV infections compared to current practice with an ICER of $1340 per infection averted. This was comparable to ART expansion alone, which would avert 37% of infections with an ICER of $1452. CONCLUSIONS: Using Uganda's gross domestic product per capita of $1681 as a threshold, PrEP and ART for high-risk persons have the potential for synergistic action and are cost-effective in preventing HIV infections in high prevalence settings. The annual cost of PrEP in this programme is less than $100 per serodiscordant couple if implemented in public clinics.

Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis.

INTRODUCTION: Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple-drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates. MATERIALS AND METHODS: We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1) current ART and PMTCT coverage, 2) current ART and high PMTCT coverage, and 3) high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART) at current coverage. RESULTS: At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results. DISCUSSION: Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels) in Uganda than South Africa. These results are likely driven by Uganda's higher fertility rates.