The long-term impact and value of curative therapy for HIV: a modelling analysis

INTRODUCTION: Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long-term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country-specific value-based prices (VBPs) of CTx. METHODS: We developed a decision-analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre-existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low-and-middle-income countries and five high-income countries, accounting for localized ART and other HIV-related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability-adjusted life-years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long-term outcomes and each country's estimated health opportunity cost, we calculated the country-specific VBP of CTx. RESULTS: The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life-years, reduced the number of individuals on ART, reduced AIDS-related deaths, and ultimately led to fewer DALYs versus ART-alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to$812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater. CONCLUSIONS: Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country

Condom use by female sex workers and their clients in Mexico: who decides and does it matter?

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Analytic Review of Modeling Studies of ARV Based PrEP Interventions Reveals Strong Influence of Drug-Resistance Assumptions on the Population-Level Effectiveness

Background Four clinical trials have shown that oral and topical pre-exposure prophylaxis (PrEP) based on tenofovir may be effective in preventing HIV transmission. The expected reduction in HIV transmission and the projected prevalence of drug resistance due to PrEP use vary significantly across modeling studies as a result of the broad spectrum of assumptions employed. Our goal is to quantify the influence of drug resistance assumptions on the predicted population-level impact of PrEP. Methods All modeling studies which evaluate the impact of oral or topical PrEP are reviewed and key assumptions regarding mechanisms of generation and spread of drug-resistant HIV are identified. A dynamic model of the HIV epidemic is developed to assess and compare the impact of oral PrEP using resistance assumptions extracted from published studies. The benefits and risks associated with ten years of PrEP use are evaluated under identical epidemic, behavioral and intervention conditions in terms of cumulative fractions of new HIV infections prevented, resistance prevalence among those infected with HIV, and fractions of infections in which resistance is transmitted. Results Published models demonstrate enormous variability in resistance-generating assumptions and uncertainty in parameter values. Depending on which resistance parameterization is used, a resistance prevalence between 2% and 44% may be expected if 50% efficacious oral PrEP is used consistently by 50% of the population over ten years. We estimated that resistance may be responsible for up to a 10% reduction or up to a 30% contribution to the fraction of prevented infections predicted in different studies. Conclusions Resistance assumptions used in published studies have a strong influence on the projected impact of PrEP. Modelers and virologists should collaborate toward clarifying the set of resistance assumptions biologically relevant to the PrEP products which are already in use or soon to be added to the arsenal against HIV

Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model

Background The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. Methods We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. Findings By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8–16·1) new infections and 1·5 million (1·4–1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78–82) reduction in incidence and a 61% (60–62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. Interpretation Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic

Consequences of a changing US strategy in the global HIV investment landscape.

OBJECTIVE: The global fight against HIV/AIDS in Africa has long been a focus of US foreign policy, but this could change if the federal budget for 2018 proposed by the US Office of Management and Budget is adopted. We aim to inform public and Congressional debate around this issue by evaluating the historical and potential future impact of US investment in the African HIV response. DESIGN/METHODS: We use a previously published mathematical model of HIV transmission to characterize the possible impact of a series of financial scenarios for the historical and future AIDS response across Sub-Saharan Africa. RESULTS: We find that US funding has saved nearly five million adults in Sub-Saharan Africa from AIDS-related deaths. In the coming 15 years, if current numbers on antiretroviral treatment are maintained without further expansion of programs (the proposed US strategy), nearly 26 million new HIV infections and 4.4 million AIDS deaths may occur. A 10% increase in US funding, together with ambitious domestic spending and focused attention on optimizing resources, can avert up to 22 million HIV infections and save 2.3 million lives in Sub-Saharan Africa compared with the proposed strategy. CONCLUSION: Our synthesis of available evidence shows that the United States has played, and could continue to play, a vital role in the global HIV response. Reduced investment could allow more than two million avoidable AIDS deaths by 2032, whereas continued leadership by the United States and other countries could bring UNAIDS targets for ending the epidemic into reach

Could misreporting of condom use explain the observed association between injectable hormonal contraceptives and HIV acquisition risk?

OBJECTIVE: Some observational studies have suggested an association between the use of hormonal contraceptives (HC) and HIV acquisition. One major concern is that differential misreporting of sexual behavior between HC users and nonusers may generate artificially inflated risk estimates. STUDY DESIGN: We developed an individual-based model that simulates the South African HIV serodiscordant couples analyzed for HC-HIV risk by Heffron et al. (2012). We varied the pattern of misreporting condom use between HC users and nonusers and reproduced the trial data under the assumption that HC use is not associated with HIV risk. The simulated data were analyzed using Cox proportional hazards models, adjusting for the reported level of condom use. RESULTS: If HC users overreport condom use more than nonusers, an apparent excess risk could be observed even without any biological effect of HC on HIV acquisition. With 45% overreporting by HC users (i.e., 9 out of every 20 sex acts reported with condoms are actually unprotected) and accurate condom reporting by nonusers, a true null effect can be inflated to give an observed hazard ratio (HR̂) of 2.0. In a different population with lower overall reported condom use, artificially high HR̂s can only be generated if non-HC users underreport condom use. CONCLUSION: Differential condom misreporting can theoretically produce inflated HR̂ values for an association between HC and HIV even without a true association. However, to produce a doubling of HIV risk that is entirely spurious requires substantially different levels of misreporting among HC users and nonusers, which may be unrealistic. IMPLICATIONS: Considerably differential amounts of condom use misreporting by HC users and nonusers would be needed to produce entirely spurious observed levels of excess HIV acquisition risk among HC users when there is actually no true association

Recent HIV prevalence trends among pregnant women and all women in sub-Saharan Africa: implications for HIV estimates

OBJECTIVES: National population-wide HIV prevalence and incidence trends in sub-Saharan Africa (SSA) are indirectly estimated using HIV prevalence measured among pregnant women attending antenatal clinics (ANC), among other data. We evaluated whether recent HIV prevalence trends among pregnant women are representative of general population trends. DESIGN: Serial population-based household surveys in 13 SSA countries. METHODS: We calculated HIV prevalence trends among all women aged 15–49 years and currently pregnant women between surveys conducted from 2003 to 2008 (period 1) and 2009 to 2012 (period 2). Log-binomial regression was used to test for a difference in prevalence trend between the two groups. Prevalence among pregnant women was age-standardized to represent the age distribution of all women. RESULTS: Pooling data for all countries, HIV prevalence declined among pregnant women from 6.5 [95% confidence interval (CI) 5.3–7.9%] to 5.3% (95% CI 4.2–6.6%) between periods 1 and 2, whereas it remained unchanged among all women at 8.4% (95% CI 8.0–8.9%) in period 1 and 8.3% (95% CI 7.9–8.8%) in period 2. Prevalence declined by 18% (95% CI −9–38%) more in pregnant women than nonpregnant women. Estimates were similar in Western, Eastern, and Southern regions of SSA; none were statistically significant (P > 0.05). HIV prevalence decreased significantly among women aged 15–24 years while increasing significantly among women 35–49 years, who represented 29% of women but only 15% of pregnant women. Age-standardization of prevalence in pregnant women did not reconcile the discrepant trends because at older ages prevalence was lower among pregnant women than nonpregnant women. CONCLUSION: As HIV prevalence in SSA has shifted toward older, less-fertile women, HIV prevalence among pregnant women has declined more rapidly than prevalence in women overall. Interpretation of ANC prevalence data to inform national HIV estimates should account for both age-specific fertility patterns and HIV-related sub-fertility