Cost-effectiveness of CRAG-LFA screening for cryptococcal meningitis among people living with HIV in Uganda.

BACKGROUND: Cryptococcal meningitis (CM) constitutes a significant source of mortality in resource-limited regions. Cryptococcal antigen (CRAG) can be detected in the blood before onset of meningitis. We sought to determine the cost-effectiveness of implementing CRAG screening using the recently developed CRAG lateral flow assay in Uganda compared to current practice without screening. METHODS: A decision-analytic model was constructed to compare two strategies for cryptococcal prevention among people living with HIV with CD4 < 100 in Uganda: No cryptococcal screening vs. CRAG screening with WHO-recommended preemptive treatment for CRAG-positive patients. The model was constructed to reflect primary HIV clinics in Uganda, with a cohort of HIV-infected patients with CD4 < 100 cells/uL. Primary outcomes were expected costs, DALYs, and incremental cost-effectiveness ratios (ICERs). We evaluated varying levels of programmatic implementation in secondary analysis. RESULTS: CRAG screening was considered highly cost-effective and was associated with an ICER of $6.14 per DALY averted compared to no screening (95% uncertainty range: $-20.32 to $36.47). Overall, implementation of CRAG screening was projected to cost $1.52 more per person, and was projected to result in a 40% relative reduction in cryptococcal-associated mortality. In probabilistic sensitivity analysis, CRAG screening was cost-effective in 100% of scenarios and cost saving (ie cheaper and more effective than no screening) in 30% of scenarios. Secondary analysis projected a total cost of $651,454 for 100% implementation of screening nationally, while averting 1228 deaths compared to no screening. CONCLUSION: CRAG screening for PLWH with low CD4 represents excellent value for money with the potential to prevent cryptococcal morbidity and mortality in Uganda.

Cryptococcal Meningitis Treatment Strategies Affected by the Explosive Cost of Flucytosine in the United States: A Cost-effectiveness Analysis.

BACKGROUND: In the United States, cryptococcal meningitis causes approximately 3400 hospitalizations and approximately 330 deaths annually. The US guidelines recommend treatment with amphotericin B plus flucytosine for at least 2 weeks, followed by fluconazole for a minimum of 8 weeks. Due to generic drug manufacturer monopolization, flucytosine currently costs approximately $2000 per day in the United States, with a 2-week flucytosine treatment course costing approximately $28 000. The daily flucytosine treatment cost in the United Kingdom is approximately $22. Cost-effectiveness analysis was performed to determine the value of flucytosine relative to alternative regimens. METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deoxycholate for 4 weeks; (2) amphotericin and flucytosine (100 mg/kg/day) for 2 weeks; and (3) amphotericin and fluconazole (800 mg/day) for 2 weeks. Costs of care were calculated using 2015 US prices and the medication costs. Survival estimates were derived from a randomized trial and scaled relative to published US survival data. RESULTS: Cost estimates were $83 227 for amphotericin monotherapy, $75 121 for amphotericin plus flucytosine, and $44 605 for amphotericin plus fluconazole. The ICER of amphotericin plus flucytosine was $23 842 per quality-adjusted life-year. CONCLUSIONS: Flucytosine is currently cost-effective in the United States despite a dramatic increase in price in recent years. Combination therapy with amphotericin and flucytosine is the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be creating access issues that will exacerbate if the trend of profiteering continues.

Financial stress is associated with reduced treatment adherence in HIV-infected adults in a resource-rich setting.

OBJECTIVES: Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. METHODS: Out-patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. RESULTS: Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P < 0.0001). In addition, 19 patients (5.7%) also stated that it was difficult or very difficult to meet travel costs to the clinic. Treatment cessation and interruption were both independently associated with difficulty meeting both pharmacy and clinic travel costs. Only 4.9% had been asked if they were having difficulty paying for medication. CONCLUSIONS: These are the first data to show that pharmacy dispensing and clinic travel costs may affect treatment adherence in a resource-rich setting. Patients should be asked if financial stress is limiting their treatment adherence.

Intravitreal ganciclovir maintenance injection for cytomegalovirus retinitis: efficacy of a low-volume, intermediate-dose regimen.

OBJECTIVE: To report the clinical outcomes of highly active antiretroviral therapy (HAART)-naïve, human immunodeficiency virus (HIV)-positive patients with newly diagnosed cytomegalovirus (CMV) retinitis receiving intravitreal injections of a low-volume intermediate maintenance dose (1.0 mg/0.02 ml) of ganciclovir. DESIGN: Nonrandomized, retrospective, interventional series. PARTICIPANTS: A consecutive cohort of 34 eyes from 24 HAART-naïve patients with AIDS and diagnosed with CMV retinitis by retinal specialists at the Singapore Communicable Disease Centre. INTERVENTION: Patients received a maintenance dose of 1.0 mg/0.02 ml of intravitreal ganciclovir once weekly after standard induction therapy with 2.0 mg/0.04 ml of twice weekly intravitreal ganciclovir. MAIN OUTCOME MEASURES: Time to progression, visual acuity, and complications. Progression was observed using photographic documentation. RESULTS: The median time to progression was 152 days (mean, 380.1 days, 95% confidence interval, 240.8-519.4). The median follow-up was 95 days (mean, 207.9 days). Three eyes developed rhegmatogenous detachments, but there was no endophthalmitis after 1858 injections. Contralateral involvement of CMV retinitis occurred in 17.6% of the patients. The cost estimate for intravitreal injections over a 6-month period was 11.7% that of sustained-release implants for unilateral treatment and 11.1% that of daily continuous intravenous infusions and oral valganciclovir compared with bilateral treatments. CONCLUSIONS: Weekly low-volume, intermediate-dose (1.0 mg/0.02 ml) ganciclovir is an efficacious option in developing countries where newer options of sustained-release implants and oral valganciclovir are unavailable or prohibitively expensive. The regimen maintains a long time to progression, preserving vision while minimizing retinal toxicity complications.

Differences in the use of health resources by Spanish and immigrant HIV-infected patients.

BACKGROUND: HIV-immigrant use of health services and related cost has hardly been analysed. We compared resource utilisation patterns and direct health care costs between Spanish and immigrant HIV-infected patients. METHODS: All HIV-infected adult patients treated during the years 2003-2005 (372 patients) in this hospital were included. We evaluated the number of out-patient, Emergency Room (ER) and Day-care Unit visits, and number and length of admissions. Direct costs were analysed. We compared all variables between immigrant and Spanish patients. RESULTS: Immigrants represented 12% (n=43) of the cohort. There were no differences in the number of out-patient, ER, and day-care hospital visits per patient between both groups. The number of hospital admissions per patient for any cause was higher in immigrant than in Spanish patients, 1.3 (4.4) versus 0.9 (2.7), P=.034. A high proportion of visits, both for the immigrant (45.1%) and Spanish patients (43.0%), took place in services other than Infectious Diseases. Mean unitary cost per patient per admission, out-patient visits and ER visits were similar between groups. Pharmacy costs per year was higher in Spanish patients than in immigrants (7351.8 versus 7153.9 euros [year 2005], P=.012). There were no differences in the total cost per patient per year between both groups. The global distribution of cost was very similar between both groups; almost 75% of the total cost was attributed to pharmacy in both groups. CONCLUSIONS: There are no significant differences in health resource utilisation and associated costs between immigrant and Spanish HIV patients.

[Assessment of the impact of the new health legislation on illegal immigrants in Spain: the case of human immunodeficiency virus infection]. / Evaluación del impacto del nuevo marco legal sanitario sobre los inmigrantes en situación irregular en España: el caso de la infección por el virus de la inmunodeficiencia humana.

The immigrant population in Spain, whether legal or not, has been entitled to healthcare under the same conditions as the Spanish population since the year 2000. The entry into vigour of the Royal Decree-Law 12/2012 of 20 April has significantly restricted this right, so that unauthorized or non-resident foreigners may now only receive emergency care, if they are under 18 or pregnant women. Out of an estimated 459,909 illegal immigrants in our country, 2,700 to 4,600 are probably infected with HIV; 1,800 to 3,220 know that they are infected, and 80% of the latter could receive antiretroviral treatment. The Royal Decree-Law is likely to cause many undesirable consequences in this population infected with HIV: increasing mortality, promoting the emergence of opportunistic diseases, increasing hospital admissions, increasing infections in the population (by HIV and other pathogens), or contributing to mother to child transmission of HIV. The expected increase in morbidity and mortality will be a greater cost in patient care, a cost which will be significantly higher in the more immunosuppressed patients. Therefore, the enforcement of the Royal Decree-Law will be much less cost-effective in the short term than was expected, and will negatively affect our country's public health, especially for those patients infected with HIV who will not be covered, thus increasing healthcare medium to long term costs, and moving away from the international health goals that were established.

Expenditures for the care of HIV-infected patients in rural areas in China's antiretroviral therapy programs.

BACKGROUND: The Chinese government has provided health services to those infected by the human immunodeficiency virus (HIV) under the acquired immunodeficiency syndrome (AIDS) care policy since 2003. Detailed research on the actual expenditures and costs for providing care to patients with AIDS is needed for future financial planning of AIDS health care services and possible reform of HIV/AIDS-related policy. The purpose of the current study was to determine the actual expenditures and factors influencing costs for untreated AIDS patients in a rural area of China after initiating highly active antiretroviral therapy (HAART) under the national Free Care Program (China CARES). METHODS: A retrospective cohort study was conducted in Yunnan and Shanxi Provinces, where HAART and all medical care are provided free to HIV-positive patients. Health expenditures and costs in the first treatment year were collected from medical records and prescriptions at local hospitals between January and June 2007. Multivariate linear regression was used to determine the factors associated with the actual expenditures in the first antiretroviral (ARV) treatment year. RESULTS: Five ARV regimens are commonly used in China CARES: zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP), stavudine (D4T) + 3TC + efavirenz (EFV), D4T + 3TC + NVP, didanosine (DDI) + 3TC + NVP and combivir + EFV. The mean annual expenditure per person for ARV medications was US$2,242 (US$1 = 7 Chinese Yuan (CNY)) among 276 participants. The total costs for treating all adverse drug events (ADEs) and opportunistic infections (OIs) were US$29,703 and US$23,031, respectively. The expenses for treatment of peripheral neuritis and cytomegalovirus (CMV) infections were the highest among those patients with ADEs and OIs, respectively. On the basis of multivariate linear regression, CD4 cell counts (100-199 cells/µL versus <100 cells/µL, P = 0.02; and ≥200 cells/µL versus <100 cells/µL, P < 0.004), residence in Mangshi County (P < 0.0001), ADEs (P = 0.04) and OIs (P = 0.02) were significantly associated with total expenditures in the first ARV treatment year. CONCLUSIONS: This is the first study to determine the actual costs of HIV treatment in rural areas of China. Costs for ARV drugs represented the major portion of HIV medical expenditures. Initiating HAART in patients with higher CD4 cell count levels is likely to reduce treatment expenses for ADEs and OIs in patients with AIDS.

[Analysis of inpatient cost of AIDS related opportunistic infection in a high HIV epidemic area].

OBJECTIVE: To analyze the inpatient cost of AIDS related opportunistic infection in a high HIV epidemic area of China. METHODS: Information was collected and analyzed from 158 inpatients with AIDS related opportunistic infection, including demographic characteristics of patients, types of opportunistic infection and treatment cost (median) from 2008 to 2010 in a high HIV epidemic area. RESULTS: The inpatient cost per visit for AIDS related opportunistic infection was 2935.7 yuan. The fee per visit for examination, laboratory test, medicine, diagnosis and treatment, nursing, bed was 132.5, 269.0, 1485.5, 367.3, 302.5 and 264.0 yuan, respectively. The inpatient cost per visit for AIDS related opportunistic infection was 4383.1 yuan for male and 3418.6 yuan for female inpatient (U = -1.279, P = 0.201). The cost per visit for AIDS related opportunistic infection was 4703.1 yuan for Han nationality and 3475.9 yuan for minority patient (U = -1.025, P = 0.305). The inpatient cost per visit for AIDS related opportunistic infection was respectively 3429.3, 5022.2, 6705.5 and 2396.7 yuan for farmers, individual businessmen, employees of enterprise and public institution and jobless (H = 28.633, P = 0.000). The cost per visit was lowest for illiteracy patients (2590.2 yuan), 3626.5 yuan for primary school, 4214.3 yuan for junior high school and 6865.8 yuan for high school and higher education (H = 10.828, P = 0.013). The cost per visit for AIDS related opportunistic infection was respectively 2873.6, 4534.3, 3077.8 and 3208.1 yuan for under the age of 29, 30-39 years old, 40-49 years old and beyond the age of 50 (H = 1.515, P = 0.679). The AIDS related opportunistic infection cost per visit for inpatients infected through sex (4621.3 yuan) was higher than that of intravenous drug users (3208.6 yuan, U = -2.588, P = 0.010). Among various types of opportunistic infections, the cost was highest for neurological diseases (5819.7 yuan), 4300.8, 2806.8, and 2083.9 yuan for respiratory diseases, digestive system diseases and skin and mucous membrane diseases, respectively (H = 15.142, P = 0.004). CONCLUSION: The study shows difference of inpatient cost per visit between subgroups, the cost of public institution was higher than that of other professions, the cost of illiteracy patients was lower than other education level, the cost of inpatients infected through sex was higher than that of intravenous drug users, the cost of neurological diseases was higher than that of other types of opportunistic infections.

Role of the US President's Emergency Plan for AIDS Relief in responding to tuberculosis and HIV coinfection.

The intersection of tuberculosis (TB) and human immunodeficiency virus (HIV) infection has eroded gains made in TB control, because previously well-functioning national TB programs have been overwhelmed by the dual challenges posed by TB and HIV coinfection. The US President's Emergency Plan for AIDS Relief (PEPFAR), through its direct support of >2.4 million persons receiving HIV treatment and, in 2009, support of >308,000 HIV-infected persons receiving TB treatment, works closely with national governments and other partners to strengthen the response to TB and HIV coinfection. PEPFAR-supported activities fall within the World Health Organization's 2004 framework for collaborative TB and HIV activities, including critical interventions to (1) develop organizational methods of collaboration across the 2 programs, (2) reduce the burden of HIV infection among patients with TB, and (3) reduce the burden of TB among persons with HIV infection or AIDS. To date, PEPFAR and partners have made important gains in coverage and scope of HIV testing, referral, and antiretroviral therapy for patients with TB. TB screening of HIV-infected patients is also beginning to increase, although greater progress needs to be made in increasing access to isoniazid preventive therapy and strengthening TB infection control. Continued strategic integration of TB and HIV interventions into PEPFAR-supported programs is essential to easing the patient burden of dual infection, improving patient outcomes, and, ultimately, decreasing rates of TB in areas with a high prevalence of TB.

Early antiretroviral therapy for patients with acute aids-related opportunistic infections: a cost-effectiveness analysis of ACTG A5164.

PURPOSE: ACTG A5164 demonstrated that early antiretroviral therapy (ART) in HIV-infected patients with acute opportunistic infections (OIs) reduced death and AIDS progression compared to ART initiation 1 month later. We project the life expectancies, costs, and incremental cost-effectiveness ratios (ICERs) of these strategies. METHOD: using an HIV simulation model, we compared 2 strategies for patients with acute OIs: (1) an intervention to deliver early ART, and (2) deferred ART. Parameters from ACTG A5164 included initial mean CD4 count (47/microL), linkage to outpatient care (87%), and immune reconstitution inflammatory syndrome 1 month after ART initiation (7%). The estimated intervention cost was $1,650/patient. RESULTS: early ART lowered projected 1-year mortality from 10.4% to 8.2% and increased life expectancy from 10.07 to 10.39 quality-adjusted life-years (QALYs). Lifetime costs increased from $385,220 with deferred ART to $397,500 with early ART, primarily because life expectancy increased, producing an ICER of $38,600/QALY. Results were most sensitive to increased intervention cost and decreased virologic efficacy in the early ART strategy. CONCLUSIONS: an intervention to initiate ART early in patients with acute OIs improves survival and meets US cost-effectiveness thresholds. Programs should be developed to implement this strategy at sites where HIV-infected patients present with OIs.

A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals.

PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Treatment of latent tuberculosis infection: An update.

Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self-administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy-in experimental studies in mice and randomized trials, largely in HIV-infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV-infected persons and children, in non-HIV-infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH-possibly because two drugs are taken rather than one. The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono-rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.

When to start antiretroviral therapy in resource-limited settings.

BACKGROUND: The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years. OBJECTIVE: To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials. DESIGN: Cost-effectiveness analysis by using a computer simulation model of HIV disease. DATA SOURCES: Published data from randomized trials and observational cohorts in South Africa. TARGET POPULATION: HIV-infected patients in South Africa. TIME HORIZON: 5-year and lifetime. PERSPECTIVE: Modified societal. INTERVENTION: No treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L. OUTCOME MEASURES: Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved. RESULTS OF SENSITIVITY ANALYSIS: Initiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%. LIMITATION: This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission. CONCLUSION: Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa.

INTRODUCTION: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3 . We investigated the cost-effectiveness of this enhanced-prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. METHODS: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standard-prophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. RESULTS: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced-prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced-prophylaxis components. Enhanced-prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced-prophylaxis still conveyed health gains in CrAg-negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost-effective unless the price of CrAg testing fell below US$2.30. CONCLUSIONS: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices.

Reduced economic burden of AIDS-defining illnesses associated with adherence to antiretroviral therapy.

OBJECTIVES: We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). METHODS AND MATERIALS: A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. RESULTS: Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1≤MPR<0.8 vs. MPR≥0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR<0.1, 0.1≤MPR<0.8, and MPR≥0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR<0.1) was larger than that in the high-adherence years (MPR≥0.8) (e.g., MPR<0.1 vs. MPR≥0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). CONCLUSIONS: Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs.

The cost of hospital care for HIV patients in Colombia: an insurer's perspective.

The aim of this study was to evaluate the cost derived from the hospitalization of people living with HIV (PLHIV) in Colombia between 2011 and 2015. This is an analysis of the direct cost of PLHIV hospitalization from the perspective of an insurer of the Colombian General Social Security System. The costs were calculated in Colombian pesos and corrected for inflation on the basis of the 2017 Consumer Price Index of the Bank of the Republic of Colombia. It was converted to US dollars at the Market Representative Exchange Rate of the same year. We analyzed 1129 hospitalizations in 612 PLHIV, of which 12% started with a diagnosis of HIV during the same hospitalization, with the majority in the AIDS stage (63%). The median overall cost of hospitalizations was US$1509 (25th and 75th percentiles: US$711-US$3254), being even higher in patients with AIDS and as the CD4 T lymphocyte count decreased. The cost derived from the medical care of PLHIV increases as the clinical control of the disease worsens, and it is a key indicator of the impact of the strategies implemented for the timely identification of the infection and subsequent management of the disease.

Cost-effectiveness of detection of intestinal amebiasis by using serology and specific-amebic-antigen assays among persons with or without human immunodeficiency virus infection.

Among 345 persons who underwent indirect hemagglutination (IHA) serological assays and assays of specific amebic antigens in their stool samples, 24 of 36 (66.7%) who were seropositive for Entamoeba histolytica had intestinal amebiasis as determined by antigen assays compared with 2 of 309 (0.2%) who were seronegative (odds ratio, 307; 95% confidence interval, 64.9 to 1,451). The estimated cost to detect a case of intestinal amebiasis by serology followed by antigen assays ($52) could be reduced by 74.3% and 69.9%, respectively, compared with the costs of the concurrent use of both assays ($202) and the antigen assays alone ($173). Our finding suggests that IHA assays followed by specific-amebic-antigen assays can be cost-effective in the diagnosis of intestinal amebiasis among persons with or without human immunodeficiency virus infection who are at risk for E. histolytica infection.

Cost of medical care for HIV-infected patients within a regional population from 1997 to 2006.

OBJECTIVES: To report on the cost of medical care for HIV-infected patients stratified by CD4 cell count for a regional population over a 9-year period, and to examine the effect of reporting costs of HIV care only or only in antiretroviral therapy (ART)-experienced patients. METHODS: Retrospective costing analysis on all HIV-infected patients within the Southern Alberta Cohort from April 1997 to April 2006. Costs for all drugs (ART/non-ART), in-patient (HIV/non-HIV) and out-patient care were obtained from primary sources. Costs were aggregated by patient's CD4 cell count and ART exposure and presented as mean cost per patient per month (PPPM) in 2006 Canadian dollars. RESULTS: The number of patients and annual costs increased by 74% and 69%, respectively. Overall mean PPPM costs increased slightly from $1082 in 1997/1998 to $1159 in 2005/2006. PPPM costs for patients with CD4 counts < or =75 cells/microL increased from $1595 to $2687 while costs for CD4 counts >500, 201-500 and 76-200 cells/microL remained relatively stable at $979, $1057 and $1294, respectively. In-patient hospitalization costs account for most of the cost increases. Reporting costs using only ART-experienced patients would overestimate total costs by 2-9%. Costs for only HIV care were 10-24% lower than total care costs. CONCLUSIONS: Care costs have remained relatively stable for most HIV patients except those with CD4 counts < or =75 cells/microL. Expensive new antiretroviral drugs have had, at present, a minimal cost impact. Enhanced testing to achieve earlier diagnosis and initiation of highly active antiretroviral therapy could potentially reduce costs of late presentation and in-patient care.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy.

BACKGROUND: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. OBJECTIVE: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. METHODS: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. RESULTS: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. CONCLUSIONS: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.