Characteristics and short- and long-term direct medical costs among adults with timely and delayed presentation for HIV care in the Netherlands.

INTRODUCTION: In Europe, half of people living with HIV (PLWH) present late to care, with associated higher morbidity and mortality. This study aims to assess short- and long-term costs of HIV-care based on time of presentation and identify other factors contributing to higher costs in the first and fifth year after antiretroviral therapy (ART) initiation. MATERIAL AND METHODS: We included ATHENA cohort data which prospectively includes 98% of PLWH in the Netherlands. PLWH who initiated ART in 2013 were included and followed over five years. PLWH were divided in three categories based on CD4 cell-count at time of ART initiation: timely presentation (CD4>350cells/µL), late presentation (CD4 200-350cells/µL or >350cells/µL with AIDS-defining illness) and very late presentation (CD4<200cells/µL). The total HIV-care cost was calculated distinguishing ART medication and non-ART medication costs (hospitalization, outpatient clinic visits, co-medications, and HIV-laboratory tests). RESULTS: From 1,296 PLWH, 273 (21%) presented late and 179 (14%) very late. Nearly half of those who entered HIV-care in a very late stage were of non-Dutch origin, with 21% originating from sub-Saharan Africa. The mean cost per patient in the first year was €12,902 (SD€11,098), of which about two-thirds due to ART (€8,250 (SD€3,142)). ART costs in the first and fifth year were comparable regardless of time of presentation. During the first year on treatment, non-ART medication costs were substantially higher among those with late presentation (€4,749 (SD€8,009)) and very late presentation (€15,886 (SD€ 21,834)), compared with timely presentation (€2,407(SD€4,511)). Higher non-ART costs were attributable to hospitalization and co-medication. The total non-ART costs incurred across five years on treatment were 56% and 246% higher for late and very late presentation respectively as compared to timely presentation. CONCLUSION: Very late presentation is associated with substantial costs, with non-ART costs nearly seven times higher than for those presenting timely. Hospitalization and co-medication costs are likely to continue to drive higher costs for individuals with late presentation into the future. Programs that identify individuals earlier will therefore likely provide significant short- and long-term health cost savings.

Cost-effectiveness and budget effect of pre-exposure prophylaxis for HIV-1 prevention in Germany from 2018 to 2058.

BackgroundPre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for men-who-have-sex-with-men (MSM). The high cost of PrEP has until recently been a primary barrier to its use. In 2017, generic PrEP became available, reducing the costs by 90%.AimOur objective was to assess cost-effectiveness and costs of introducing PrEP in Germany.MethodsWe calibrated a deterministic mathematical model to the human immunodeficiency virus (HIV) epidemic among MSM in Germany. PrEP was targeted to 30% of high-risk MSM. It was assumed that PrEP reduces the risk of HIV infection by 85%. Costs were calculated from a healthcare payer perspective using a 40-year time horizon starting in 2018.ResultsPrEP can avert 21,000 infections (interquartile range (IQR): 16,000-27,000) in the short run (after 2 years scale-up and 10 years full implementation). HIV care is predicted to cost EUR 36.2 billion (IQR: 32.4-40.4 billion) over the coming 40 years. PrEP can increase costs by at most EUR 150 million within the first decade after introduction. Ten years after introduction, PrEP can become cost-saving, accumulating to savings of HIV-related costs of EUR 5.1 billion (IQR: 3.5-6.9 billion) after 40 years. In a sensitivity analysis, PrEP remained cost-saving even at a 70% price reduction of antiretroviral drug treatment and a lower effectiveness of PrEP.ConclusionIntroduction of PrEP in Germany is predicted to result in substantial health benefits because of reductions in HIV infections. Short-term financial investments in providing PrEP will result in substantial cost-savings in the long term.

Early treatment of acute hepatitis C infection is cost-effective in HIV-infected men-who-have-sex-with-men.

BACKGROUND: Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. METHODS: We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. RESULTS: Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. CONCLUSIONS: Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.

Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation. METHODS: We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below €20 000 were considered to be cost-effective in this analysis. FINDINGS: Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as €11 000 (IQR 9400-14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as €2000 (IQR 1300-3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30-40%. INTERPRETATION: PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving. FUNDING: None.

Partner Notification for Reduction of HIV-1 Transmission and Related Costs among Men Who Have Sex with Men: A Mathematical Modeling Study.

BACKGROUND: Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch men-who-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. METHODS: Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a 20 year period. RESULTS: Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in the short term, with increasing cost-effectiveness over time: from €41,476 -€41, 736 (IQR €40,529-€42,147; €40,791-€42,397) to €5,773 -€5,887 (€5,134-€7,196; €5,411-€6,552) per QALY gained over a 5 and 20 year period, respectively. The full monetary benefits of partner notification by preventing new HIV infections become more apparent over time. CONCLUSIONS: Partner notification will not lead to the end of the HIV epidemic, but will prevent new infections and be increasingly cost-effectiveness over time.

Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study.

INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2-7.2%) in 2014, to 6.8% (IQR 6.1-7.6%), 10.0% (IQR 8.9-11.5%) and 11.1% (IQR 9.7-13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4-8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1-10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from $1612 to $2234 (IQR $450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority.

Cost-effectiveness of PrEP in HIV/AIDS control in Zambia: a stochastic league approach.

BACKGROUND: Earlier antiretroviral therapy initiation and pre-exposure prophylaxis (PrEP) prevent HIV, although at a substantial cost. We use mathematical modeling to compare the cost-effectiveness and economic affordability of antiretroviral-based prevention strategies in rural Macha, Zambia. METHODS: We compare the epidemiological impact and cost-effectiveness over 40 years of a baseline scenario (treatment initiation at CD4 <350 cells/µL) with treatment initiation at CD4 <500 cells per microliter, and PrEP (prioritized to the most sexually active, or nonprioritized). A strategy is cost effective when the incremental cost-effectiveness ratio (ICER) is <$3480 (<3 times Zambian per capita GDP). Stochastic league tables then predict the optimal intervention per budget level. RESULTS: All scenarios will reduce the prevalence from 6.2% (interquartile range, 5.8%-6.6%) in 2014 to about 1% after 40 years. Compared with the baseline, 16% of infections will be averted with prioritized PrEP plus treatment at CD4 <350, 34% with treatment at CD4 <500, and 59% with nonprioritized PrEP plus treatment at CD4 <500. Only treating at CD4 <500 is cost effective: ICER of $62 ($46-$75). Nonprioritized PrEP plus treating at CD4 <500 is borderline cost effective: ICER of $5861 ($3959-$8483). Initiating treatment at CD4 <500 requires a budget increase from $20 million to $25 million over 40 years, with a 96.7% probability of being the optimal intervention. PrEP should only be considered when the budget exceeds $180 million. CONCLUSIONS: Treatment initiation at CD4 <500 is a cost-effective HIV prevention approach that will require a modest increase in budget. Although adding PrEP will avert more infections, it is not economically feasible, as it requires a 10-fold increase in budget.

Cost-effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV-1 infections in rural Zambia: a modeling study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia. METHODS: A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4<350 cells/mm(3). We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5-15% of the total population), versus randomly putting 40-60% of the total population on PrEP. RESULTS: Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios. CONCLUSIONS: Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect.

Low cost HIV-1 quantitative RT-PCR assay in resource-limited settings: improvement and implementation.

Monitoring of HIV viral load in low and middle income settings is limited by high cost of the commercial assays. Therefore, we developed a novel RT-PCR quantitative assay was developed. This assay targets the HIV-1 pol integrase gene (INT). Subsequently, the performance of the INT assay, described previously as a Long Terminal Repeat (LTR) assay and a combined INT/LTR dual target RT-PCR assay was compared. The LTR-assay was found to be sensitive and cost-effective (50-70% cheaper than commercial assays) with the lowest coefficient of variation (%CV). Introduction of an internal standard further improved assay reliability. Therefore, this LTR assay was implemented in West Java, Indonesia. Linearity and precision of the LTR assay were good: %CV ranged from 1.0% to 10.4%. The limit of quantitation was 616 copies/ml. Performance was comparable with the commercial assay (Abbott assay) (r(2)=0.01), although on average the viral loads were 0.39 log(10)copies/ml lower. In clinical practice, it had excellent capability for monitoring treatment failure, the positive predictive value was 99% and the negative predictive value was 93%. In conclusion, the implementation of the improved HIV-1 viral load LTR-assay for routine diagnosis in resource poor settings can be a good alternative when commercial assays are unaffordable.