Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis.

INTRODUCTION: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. METHODS: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). RESULTS: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. CONCLUSIONS: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Cost-per-diagnosis as a metric for monitoring cost-effectiveness of HIV testing programmes in low-income settings in southern Africa: health economic and modelling analysis.

INTRODUCTION: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric. METHODS: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars). RESULTS: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum. CONCLUSIONS: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes.

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.

BACKGROUND: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. METHODS: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. RESULTS: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). CONCLUSIONS: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

The impact and cost-effectiveness of community-based HIV self-testing in sub-Saharan Africa: a health economic and modelling analysis.

INTRODUCTION: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost-effectiveness of community-based HIV self-testing (CB-HIVST) is unclear. We aimed to assess this in different sub-populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub-Saharan Africa. METHODS: The synthesis model was used to address this aim. Three sub-populations were considered for CB-HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB-HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB-HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five-year time-limited CB-HIVST programme. Cost-effectiveness was defined by an incremental cost-effectiveness ratio (ICER; cost-per-disability-adjusted life-year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB-HIVST was evaluated using the number of additional tests per infection or death averted. RESULTS: In the base case, targeting adult men with CB-HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost-effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB-HIVST to WTS was the most cost-effective. The main drivers of cost-effectiveness were the cost of CB-HIVST and the prevalence of undiagnosed HIV. All other CB-HIVST scenarios had an ICER above US$500 per DALY averted. CONCLUSIONS: CB-HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB-HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub-population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost-effectiveness.

Improving survival of retinoblastoma in Uganda.

BACKGROUND: Diagnostic delay results in relatively high mortality among children with retinoblastoma in Uganda, where treatment was limited to surgery and, for some, radiotherapy. In order to improve outcomes, a simple programme of neoadjuvant and adjuvant chemotherapy was introduced. Here we report survival before and after this change to medical practice. METHODS: Affordable standard off-patent chemotherapy agents were administered by trained paramedical staff to groups of patients at the same time. Survival before and after the introduction of chemotherapy was monitored. Between 2006 and 2013 a total of 270 patients with retinoblastoma were included, 181 treated prior to chemotherapy and 89 after (beginning in 2009). We had 94% follow-up and 249 had histological verification of diagnosis. RESULTS: Using a proportional hazards model adjusted for age, sex and laterality, children treated after chemotherapy was introduced had a 37% lower risk of dying (HR 0.63, 95% CI 0.41 to 0.99) compared with children treated before. Prior to the introduction of chemotherapy only 15% of children who survived bilateral disease retained vision after treatment compared with 71% after chemotherapy. CONCLUSIONS: The introduction of chemotherapy proved safe and cost-effective in non-specialist hands and was associated with significant improvements in survival and, among bilateral cases, in preserving vision.