Faculty Bibliography

OBJECTIVE:: To compare the value and effectiveness of different prioritization strategies of pre-exposure prophylaxis (PrEP) in New York City (NYC). DESIGN:: Mathematical modelling utilized as clinical trial is not feasible. METHODS:: Using a model accounting for both sexual and parenteral transmission of HIV, we compare different PrEP prioritization strategies (PPS) with two scenarios - no PrEP and PrEP for all susceptible at-risk individuals. The PPS included PrEP for all MSM, only high-risk MSM, high-risk heterosexuals, and IDUs, and all combinations of these four strategies. Outcomes included HIV infections averted, and incremental cost-effectiveness (per-infection averted) ratios. Initial assumptions regarding PrEP included a 44% reduction in HIV transmission, 50% uptake in the prioritized population and an annual cost per person of $9762. Sensitivity analyses on key parameters were conducted. RESULTS:: Prioritization to all MSM results in a 19% reduction in new HIV infections. Compared with PrEP for all persons at-risk, this PPS retains 79% of the preventive effect at 15% of the total cost. PrEP prioritized to only high-risk MSM results in a reduction in new HIV infections of 15%. This PPS retains 60% of the preventive effect at 6% of the total cost. There are diminishing returns when PrEP utilization is expanded beyond this group. CONCLUSION:: PrEP implementation is relatively cost-inefficient under our initial assumptions. Our results suggest that PrEP should first be promoted among MSM who are at particularly high risk of HIV acquisition. Further expansion beyond this group may be cost-effective, but is unlikely to be cost-saving.

BACKGROUND: HIV remains a major cause of preventable morbidity and mortality in Kenya. The effects of behaviors that accompany unhealthy alcohol consumption are a pervasive risk factor for HIV transmission and progression. Our objective was to estimate the portion of HIV infections attributable to unhealthy alcohol use and to evaluate the impact of hypothetical interventions directed at unhealthy alcohol use on HIV infections and deaths. METHODS: We estimated outcomes over a time horizon of 20 years using a computer simulation of the Kenyan population. This computer simulation integrates a compartmental model of HIV transmission with a mechanistic model of HIV progression that was previously validated in sub-Saharan Africa. Integration of the transmission and progression models allows simultaneous consideration of alcohol's effects on HIV transmission and progression (e.g., lowering antiretroviral adherence may increase transmission risk by elevating viral load, and may simultaneously increase progression by increasing the likelihood of AIDS). The simulation considers important aspects of heterogeneous sexual mixing patterns, including assortativeness of partners by age and activity level, age-discordant relationships, and high activity subgroups. Outcomes included number of new HIV infections, number of AIDS deaths, and infectivity (number of new infections per infected person per year). RESULTS: Our model estimated that the effects of behaviors accompanying unhealthy alcohol consumption are responsible for 13.0% of new HIV infections in Kenya. An alcohol intervention with effectiveness similar to that observed in a published randomized controlled trial of a cognitive-behavioral therapy-based intervention in Kenya (45% reduction in unhealthy alcohol consumption) could prevent nearly half of these infections, reducing their number by 69,858 and reducing AIDS deaths by 17,824 over 20 years. Estimates were sensitive to assumptions with respect to the magnitude of alcohol's underlying effects on condom use, antiretroviral therapy adherence, and sexually transmitted infection prevalence. CONCLUSIONS: A substantial number of new HIV infections in Kenya are attributable to unhealthy alcohol use. An alcohol intervention with the effectiveness observed in a published randomized controlled trial has the potential to reduce infections over 20 years by nearly 5% and avert nearly 18,000 deaths related to HIV.

BACKGROUND: Outbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population. METHODS/DESIGN: Eligible studies will include quantitative empirical data related to sexual transmission of HCV in HIV-positive MSM, including data describing incidence or prevalence, and associations between risk factors or interventions and the occurrence or progression of HCV disease. Care will be taken to ensure that HCV transmission related to injection drug use is excluded from the incidence estimates. Scientific databases will be searched using a comprehensive search strategy. Proceedings of scientific conferences, reference lists and personal files will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle-Ottawa scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis. DISCUSSION: HIV-positive MSM are a key HCV-affected population in the US and other high-income countries. This review seeks to identify modifiable risk factors and settings that will be the target of interventions, and will consider how to constitute a portfolio of interventions to deliver the greatest health benefit. This question must be considered in relation to the magnitude of HCV infection and its consequences in other key affected populations, namely, young prescription opioid users who have transitioned to illicit opiate injection, and older injection drug users among whom HCV prevalence and incidence are extremely high. This review is part of a series of systematic reviews and meta-analyses that will synthesize the evidence across all these population groups and develop recommendations and decision tools to guide public health resource allocation. TRIAL REGISTRATION: PROSPERO registration number: CRD42013006462.

BACKGROUND: Increased eligibility guidelines of antiretroviral therapy (ART) may lead to greater routine viral load monitoring. However, in resource-constrained settings, the additional resources required by greater routine viral load monitoring may impair ability to comply with expanded eligibility guidelines for ART. OBJECTIVE: We use a published validated computer simulation of the HIV epidemic in East African countries (expanded to include transmission as well as disease progression) to evaluate the cost-effectiveness of routine viral load monitoring. METHODS: We explored alternative scenarios regarding cost, frequency, and switching threshold of routine viral load monitoring (including every 6 or every 12 months; and switching thresholds of 1000, or 10 000 copies/ml), as well as alternative scenarios regarding ART initiation (200, 350, 500 cells/mul, and no CD4 cell threshold). For each ART initiation strategy, we sought to identify the viral load monitoring strategy at which the incremental cost-effectiveness ratio (ICER) of more frequent routine viral load testing became more favorable than the ICER of more expansive ART eligibility. Cost inputs were based on data provided by the Academic Model Providing Access to Healthcare (AMPATH), and disease progression inputs were based on prior published work. We used a discount rate of 3%, a time horizon of 20 years, and a payer perspective. RESULTS: Across a wide range of scenarios, and even when considering the beneficial effect of virological monitoring at reducing HIV transmission, earlier ART initiation conferred far greater health benefits for resources spent than routine virological testing, with ICERs of approximately $1000 to $2000 for earlier ART initiation, versus ICERs of approximately $5000 to $25 000 for routine virological monitoring. ICERs of viral load testing were insensitive to the cost of the viral load test, because most of the costs originated from the downstream higher costs of later regimens. ICERs of viral load testing were very sensitive to the relative cost of second-line compared with first-line regimens, assuming favorable value when the costs of these regimens were equal. CONCLUSION: If all HIV patients are not yet treated with ART starting at 500 cells/mul and costs of second regimens remain substantially more expensive than first-line regimens, resources would buy more population health if they are spent on earlier ART rather than being spent on routine virological testing.

BACKGROUND:WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. METHODS:We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. FINDINGS/RESULTS:All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. INTERPRETATION/CONCLUSIONS:The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. FUNDING/BACKGROUND:Bill & Melinda Gates Foundation, WHO.

PURPOSE OF REVIEW: To summarize recent cost-effectiveness analyses (CEAs) that evaluate optimal treatment strategies for persons living with HIV/AIDS (PLWHA). RECENT FINDINGS: Efforts to attain universal coverage of current treatment guidelines (e.g., initiation at CD4 cell count <350 cells/mul) are generally very costeffective. Expansion of access beyond current guidelines will additionally improve clinical outcomes and aversion of new HIV infections; however, cost-effectiveness is more uncertain. Increasing access to antiretroviral therapy (ART) offers greater health benefit than investing the same funds in intensive laboratory monitoring for those on ART, particularly in those settings in which universal coverage has not yet been attained. Recommended ART regimens (e.g., tenofovir) have favorable cost-effectiveness when compared with substitution of newer, more expensive agents (e.g., rilpivirine, darunavir) or substitution of older, cheaper alternatives that are more toxic (e.g., stavudine). SUMMARY: There is increasing use of CEA to evaluate decisions regarding HIV treatment in order to buy the most 'health' with limited resources. Expansion of ART access provides substantial clinical and preventive benefit and offers favorable cost-effectiveness. Intensive laboratory monitoring may not be the highest priority in settings in which resources are constrained. Further work on the economic impact, clinical effectiveness, and feasibility of ART treatment for all (e.g., no CD4 cell initiation criteria) is needed.

Abstract Objective: This study aims to describe the final adult height (FAH) and pubertal growth patterns in human immunodeficiency virus (HIV)-infected adolescents and to compare these to an age-matched population of seroreverting HIV-exposed, uninfected (HEU) adolescents. It further aims to evaluate the interplay of proinflammatory cytokines with insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and IGFBP-1 during the pubertal growth spurt. Methods: HIV-infected (n=34) and HEU (n=12) adolescents who had achieved FAH were evaluated. Auxologic data, viral load, CD4+ T-lymphocyte (CD4) count, and the use of highly active antiretroviral therapy were obtained via a retrospective chart review. Serum interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, IGFBP-1, IGFBP-3, and IGF-1 were assessed. Results: The mean FAH standard deviation score for the HIV-infected group was -0.78 (+/-1.1) compared to 0.05 (+/-0.78) for the HEU (p=0.034). There was a positive correlation between CD4 count and FAH (p=0.019). The mean age and magnitude of peak growth velocity (GV) was within normal limits. IL-1alpha, IL-6, TNF-alpha, IGFBP-3, and IGF-1 were not significantly correlated with HIV RNA or height. IGFBP-1 was detectable in 100% of poorly controlled HIV-infected patients and 25% of the HEU cohort (p=0.0003). Conclusions: The FAH of HIV-infected patients was significantly shorter than that of HEU patients, and it positively correlated with CD4 count. Our cohort demonstrated normal timing and magnitude of peak GV during puberty.

BACKGROUND: New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically. METHODS: A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC. RESULTS: Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than $360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be $106,378; the total cost was in excess of $2 billion (over the 20 year period, or approximately $100 million per year, on average). The cost-savings of prevented infections was estimated at more than $5 billion (or approximately $250 million per year, on average). CONCLUSIONS: Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs.