Analysis of Health-Related Quality of Life and Incurred Costs Among Human Immunodeficiency Virus, Tuberculosis, and Tuberculosis/HIV Coinfected Outpatients in Indonesia.

OBJECTIVES: A growing interest in healthcare costs and patients' health-related quality of life (HRQoL) exists in the context of the increasing importance of health technology assessment in countries with high numbers of the HIV and tuberculosis (TB) patient populations, such as Indonesia. This study aimed to analyze the HRQoL and out-of-pocket (OOP) costs of HIV, TB, and TB/HIV coinfected participants in a city in Indonesia with a high prevalence of HIV and TB. METHODS: A cross-sectional survey was conducted in the voluntary counseling and testing and lung clinics of Bekasi City Public Hospital (Indonesia) from January to March 2018. Patients' HRQoL was measured using the EQ-5D-5L questionnaire, whereas OOP costs were extracted from a semistructured questionnaire. RESULTS: Of the 460 eligible participants, 82% resided in the city, 48% of them were married, and their median age was 34 years. Less than half were insured, and more than half had no source of income. The median values of health utilities for participants with HIV, TB, and TB/HIV were perceived as potentially high (1.0, 0.9, and 0.8, respectively). The TB/HIV coinfected outpatients had the highest OOP costs (US$94.5), with the largest contribution coming from direct medical OOP expenditures. Taking loans from family members was adopted as a financial strategy to overcome inadequate household incomes and high treatment costs. CONCLUSION: This study suggests that TB/HIV coinfection potentially lowers HRQoL and increases healthcare costs and the need for economic analysis to underpin cost-effective treatment in such patients.

Evaluation of cost-effectiveness of peginterferon plus ribavirin for chronic hepatitis C treatment and direct-acting antiviral agents among HIV-infected patients in the prison and community settings.

BACKGROUND: In Taiwan, the majority of chronic hepatitis C carriers with HIV co-infection are intravenous drug users and inmates in correctional facilities. Peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (HCV) infection more than decades. We evaluated the estimated cost-effectiveness of PegIFN/RBV from the National Health Insurance Research Database, covering the population of Taiwan from 1998 to 2013. MATERIALS AND METHODS: This is an observational study, and study during was 2010-2016 and a total of 239 patients were treated with PegIFN/RBV. Of them, 156 patients were treated in the correctional facilities of Taipei, Taoyuan, Taichung and Taitung prisons, and 83 patients were treated in communities. The cost-effectiveness was analyzed in regimens of PegIFN/RBV and direct-acting antiviral agents. RESULTS: By multivariate analysis, the patients completed PegIFN/RBV in prison (adjusted odds ratio [aOR]: 4.56, 95% confidence interval [CI]: 1.58-13.12, p = 0.005), HCV RNA level <800,000 IU/mL (aOR: 4.0, 95% CI: 1.27-12.66, p = 0.02) at baseline, and the presence of early virologic response (EVR) (aOR: 7.67, 95% CI: 1.89-31.06, p = 0.004) were independent predictors for sustained virologic response (SVR). For the subgroups of prisoners, HIV-infected prisoners and HIV-infected patients in communities, the SVR rate was 73.8%, 72.0% and 36.8%, and the average medical-care cost was US$7,701, $7,893, and $15,443 per SVR achieved, respectively. Also, the estimated medical-care cost for genotype 6 was US$9211. CONCLUSIONS: Chronic HCV/HIV co-infected patients with genotype 1 and 6 in the community setting could benefit from DAAs in Taiwan.

National estimates of case-mix, mortality, and economic outcomes among inpatient HIV/AIDS mono-infection and hepatitis C co-infection cases in the US.

RATIONALE, AIMS, AND OBJECTIVES: To assess inpatient clinical and economic outcomes for AIDS/HIV and Hepatitis C (HCV) co-infection in the United States from 2003 to 2014. METHOD: This historical cohort study utilized nationally representative hospital discharge data to investigate inpatient mortality, length of stay (LoS), and inflation-adjusted charges among adults (≥18 years). Outcomes were analysed via multivariable generalized linear models according to demographics, hospital and clinical characteristics, and AIDS/HIV or HCV sequelae. RESULTS: Overall, 17.8% of the 2.75 million estimated AIDS/HIV inpatient cases involved HCV from 2003 to 2014, averaging 48.5 ± 9.0 years of age and 68.0% being male. Advanced sequalae of AIDS and HCV incurred a LoS of 10.3 ± 11.9 days, charges of $88 789 ± 131 787, and a 16.9% mortality. Many cases involved noncompliance, tobacco use disorders, and substance abuse. Although mortality decreased over time, multivariable analyses indicated that poorer outcomes were generally associated with more advanced clinical conditions and AIDS-associated sequalae, although mixed results were observed for specific manifestations of HCV. Rural residence was independently associated with a 3.26 times higher adjusted odds of mortality from 2009 to 2014 for HIV/HCV co-infection (P < 0.001), although not for AIDS/HCV (OR = 1.38, P = 0.166). CONCLUSION: Given the systemic nature and modifiable risks inherent within coinfection, more proactive screening and intervention appear warranted, particularly within rural areas.

Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre- vs posttransplant.

Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.

Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa.

INTRODUCTION: The World Health Organization recommends point-of-care (POC) lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in selected human immunodeficiency virus (HIV) positive people. South Africa had 438 000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive people. LF-LAM is being considered for scale-up in South Africa. METHODS: We estimated the costs of using LF-LAM in HIV-positive adults with CD4 counts  150 cells/µl enrolled in the TB Fast Track Trial in South Africa. We also estimated costs of POC haemoglobin (Hb), as this was used in the study algorithm. Data on clinic-level (10 intervention clinics) and above-clinic-level costs were collected. RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics over 24 months. The mean clinic-level costs were US$12.80 per patient for LF-LAM and POC Hb; LF-LAM costs were US$11.49 per patient. The mean above-clinic-level unit costs for LF-LAM were US$12.06 for clinic preparation, training, coordination and mentoring. The mean total cost of LF-LAM was US$23.55 per patient. CONCLUSION: At clinic level, the cost of LF-LAM was comparable to other TB diagnostics in South Africa. It is important to consider above-clinic-level costs for POC tests, as these may be required to support roll-out and ensure successful implementation.

Household contact non-attendance of clinical evaluation for tuberculosis: a pilot study in a high burden district in South Africa.

BACKGROUND: In 2012, the World Health Organization launched guidelines for systematically investigating contacts of persons with infectious tuberculosis (TB) in low- and middle-income countries. As such, it is necessary to understand factors that would influence successful scale-up. This study targeted household contacts of newly-diagnosed infectious TB patients in the Mangaung Metropolitan district to explore factors associated with non-attendance of clinical evaluation. METHOD: In September-October 2016, a pilot study of household contacts was conducted. At each of the 40 primary health care (PHC) facilities in the district, at least one out of four types of TB index cases were purposefully selected. These included children <5 years, smear-positive cases, HIV co-infected cases, and multidrug-resistant TB (MDR-TB) cases. Trained fieldworkers administered questionnaires and screened contacts for TB symptoms. Those with TB symptoms as well as children <5 years were referred for clinical evaluation at the nearest PHC facility. Contacts' socio-demographic and clinical characteristics, TB knowledge and perception about TB-related discrimination are described. Logistic regression analysis was used to investigate factors associated with non-attendance of clinical evaluation. RESULTS: Out of the 259 participants, approximately three in every five (59.5%) were female. The median age was 20 (interquartile range: 8-41) years. While the large majority (87.3%) of adult contacts correctly described TB aetiology, almost three in every five (59.9%) thought that it was hereditary, and almost two-thirds (65.5%) believed that it could be cured by herbal medicine. About one-fifth (22.9%) of contacts believed that TB patients were subjected to discrimination. Two in every five (39.4%) contacts were referred for clinical evaluation of whom more than half (52.9%) did not attend the clinic. Non-attendance was significantly associated with inter alia male gender (AOR: 3.4; CI: 1.11-10.24), prior TB diagnosis (AOR: 5.6; CI: 1.13-27.90) and sharing of a bedroom with the index case (AOR: 3.4: CI: 1.07-10.59). CONCLUSION: The pilot study identified gaps in household contacts' knowledge of TB. Further research on important individual, clinical and structural factors that can influence and should be considered in the planning, implementation and scale-up of household contact TB investigation is warranted.

Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil.

OBJECTIVE: The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). METHODS: We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV). RESULTS: Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882. CONCLUSIONS: Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB. TRIAL REGISTRATION NUMBER: RBR-22t943, Results.

Incremental Cost Effectiveness of Bedaquiline for the Treatment of Rifampicin-Resistant Tuberculosis in South Africa: Model-Based Analysis.

BACKGROUND: Nearly 20,000 people were diagnosed with multi-drug and rifampicin-resistant tuberculosis (MDR/RR-TB) in South Africa in 2015, yet only one-half of the patients who start treatment are expected to have a successful outcome. There is increasing evidence of the effectiveness and safety of new drug regimens containing bedaquiline for MDR/RR-TB; however, whether they are affordable for high-burden, limited-resource settings is uncertain. OBJECTIVE: Our objective was to determine the incremental cost effectiveness of a bedaquiline-based regimen for MDR/RR-TB treatment in South Africa compared with the standard kanamycin-based regimen. METHODS: We established a Markov model for ambulatory treatment of MDR/RR-TB in a high-HIV prevalence setting, parameterized using clinical outcomes from the South African National TB Programme (SA NTP) before (2012-2014) and after (2015-2016) bedaquiline roll-out. The effectiveness of treatment was evaluated in disability-adjusted life-years (DALYs). Ingredient costs from the provider's perspective were collected in 2016 South African Rand and converted to $US, including bedaquiline at $US675.23 per 6-month treatment course. Culture conversion rates were derived from the phase IIb trial of bedaquiline, and disability adjustments were adapted from published literature. Costs and effectiveness were discounted at 3%. RESULTS: For non-bedaquiline regimens, the total expected cost over the 10-year time horizon for a patient with MDR/RR-TB was $US4439 with disability-adjusted survival of 5.1 years. Replacing capreomycin with bedaquiline in patients who failed MDR/RR-TB treatment and required treatment for extensively drug-resistant (XDR-TB) resulted in cost savings ($US4356; 1.8% less) and similar effectiveness (0.02 DALYs averted). As a result, the standard regimen (no bedaquiline) was dominated. Replacing kanamycin with bedaquiline to provide all patients with MDR/RR-TB access to bedaquiline cost $US4647 (4.3% more) and averted 0.17 DALYs compared with the no bedaquiline regimen. The incremental cost-effectiveness ratio was $US1242/DALY averted. CONCLUSION: Markov modelling indicates providing bedaquiline for all patients with MDR/RR-TB could increase the 24-month treatment success rate in South Africa from 56.3% using the current regimen to 60.6%, at a cost $US2.6 million over a 10-year horizon, less than 1% of the estimated $US425 million SA NTP annual budget.

Hospital length of stay and cost burden of HIV, tuberculosis, and HIV-tuberculosis coinfection among pregnant women in the United States.

BACKGROUND: We sought to determine hospital length of stay (LOS) and cost burden associated with hospital admissions among pregnant women with HIV monoinfection, tuberculosis (TB) monoinfection, or HIV-TB coinfection in the United States. METHODS: Analysis covered the period from 2002-2014 using data from the Nationwide Inpatient Sample. Relevant ICD-9-CM codes were used to determine HIV and TB status. Costs associated with hospitalization were calculated and adjusted to 2010 dollars using the medical care component of the Consumer Price Index. RESULTS: We found modest annual average reduction in HIV, TB, and HIV-TB coinfection rates over the study period. The mean LOS was lowest among mothers free of HIV or TB disease and highest among those with HIV-TB coinfection. The average LOS among mothers diagnosed with TB monoinfection was 60% higher than for those with HIV monoinfection. The cost associated with pregnancy-related hospital admissions among mothers with HIV was approximately 30% higher than disease-free mothers, and the cost more than doubled among patients with TB monoinfection or HIV-TB coinfection. CONCLUSIONS: TB significantly increased hospital care cost among HIV-positive and HIV-negative pregnant women.

Recognizing the impact of endemic hepatitis D virus on hepatitis B virus eradication.

BACKGROUND: Hepatitis delta virus (HDV) in conjunction with hepatitis B virus (HBV) increases adult morbidity and mortality. A number of studies have performed cost-benefit analyses for HBV interventions, but they have ignored the impact of HDV on these outcomes. METHODS: Using a mathematical model of HBV-HDV epidemiology, we compare health benefits and cost outcomes of four interventions: testing with HBV adult vaccination (diagnosis), diagnosis with antiviral treatment for HBV infections (mono-infections), diagnosis with antiviral treatment for HBV-HDV infections (dual-infections), and awareness programs. The relationship between optimal levels and outcomes of each of these interventions and HDV prevalence in HBV infected individuals ranging from 0 to 50% is determined. RESULTS: Over a 50 year period under no intervention, HBV prevalence, per capita total cost and death toll increase by 2.25%, -$11 and 2.6-fold respectively in moderate HDV endemic regions compared to mono-infected regions; the corresponding values for high HDV endemic regions are 4.2%, -$21 and 3.9-fold. Optimal interventions can be strategized similarly in mono and dually endemic regions. Only implementation of all four interventions achieves a very low HBV prevalence of around 1.5% in a moderate HDV endemic region such as China, with 2.8 million fewer deaths compared to no intervention. Although the policy of implementation of all four interventions costs additional $382 billion compared to no intervention, it still remains cost-effective with an incremental cost-effectiveness ratio of $1400/QALY. Very high efficacy awareness programs achieve less prevalence with fewer deaths at a lower cost compared to treatment and/or vaccination programs. CONCLUSION: HDV substantially affects the performance of any HBV-related intervention. Its exclusion results in over-estimation of the effectiveness of HBV interventions.

Ending tuberculosis by 2030: can we do it?

The Sustainable Development Goals aim to end tuberculosis (TB) related deaths, transmission and catastrophic costs by 2030. Multisectorial action to accelerate socio-economic development, a new vaccine and novel diagnostics and medicines for treatment are key advances needed to end TB transmission. Achieving 90-90-90 targets for TB (i.e., 90% of vulnerable populations screened, 90% diagnosed and started on treatment, and at least 90% cured) will help accelerate progress towards reductions in mortality; however, passive case detection strategies, multidrug-resistant TB, human immunodeficiency virus coinfection and outdated pathways to care need to be overcome. Ending the catastrophic costs associated with TB will require expansion of health insurance coverage, comprehensive coverage of TB services, and limited indirect costs by vulnerable and poor populations.

Toxoplasmosis and Toxocariasis: An Assessment of Human Immunodeficiency Virus Comorbidity and Health-Care Costs in Canada.

Toxoplasma gondii and Toxocara spp. are zoonotic parasites with potentially severe long-term consequences for those infected. We estimated incidence and investigated distribution, risk factors, and costs associated with these parasites by examining hospital discharge abstracts submitted to the Canadian Institute for Health Information (2002-2011). Annual incidence of serious toxoplasmosis and toxocariasis was 0.257 (95% confidence interval [CI]: 0.254-0.260) and 0.010 (95% CI: 0.007-0.014) cases per 100,000 persons, respectively. Median annual health-care costs per serious case of congenital, adult-acquired, and human immunodeficiency virus (HIV)-associated toxoplasmosis were $1,971, $763, and $5,744, respectively, with an overall cost of C$1,686,860 annually (2015 Canadian dollars). However, the total economic burden of toxoplasmosis is likely much higher than these direct health-care cost estimates. HIV was reported as a comorbidity in 40% of toxoplasmosis cases and accounted for over half of direct health-care costs associated with clinical toxoplasmosis. A One Health approach, integrating physician and veterinary input, is recommended for increasing public awareness and decreasing the economic burden of these preventable zoonoses.

Labour productivity losses caused by premature death associated with hepatitis C in Spain.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection places a huge burden on healthcare systems. There is no study assessing the impact of HCV infection on premature deaths in Spain. The aim of this study was to estimate productivity losses because of premature deaths attributable to hepatitis C occurring in Spain during 2007-2011. MATERIALS AND METHODS: We use data from several sources (Registry of Deaths, Labour Force Survey and Wage Structure Survey) to develop a simulation model based on the human capital approach and to estimate the flows in labour productivity losses in the period considered. The attributable fraction method was used to estimate the numbers of deaths associated with HCV infection. Two sensitivity analyses were developed to test the robustness of the results. RESULTS: Our model shows total productivity losses attributable to HCV infection of 1054.7 million euros over the period analysed. The trend in productivity losses is decreasing over the period. This result is because of improvements in health outcomes, reflected in the reduction of the number of years of potential productive life lost. Of the total estimated losses, 18.6% were because of hepatitis C, 24.6% because of hepatocellular carcinoma, 30.1% because of cirrhosis, 15.9% because of other liver diseases and 10.7% because of HIV-HCV coinfection. CONCLUSION: The results show that premature mortality attributable to hepatitis C involves significant productivity losses. This highlights the need to extend the analysis to consider other social costs and obtain a more complete picture of the actual economic impact of hepatitis C infection.

Effect of management strategies and clinical status on costs of care for advanced HIV.

OBJECTIVES: To determine the association between preexisting characteristics and current health and the cost of different types of advanced human immunodeficiency virus (HIV) care. METHODS: Treatment-experienced patients failing highly active antiretroviral treatment (ART) in the United States, Canada, and the United Kingdom were factorial randomized to an antiretroviral-free period and ART intensification. Cost was estimated by multiplying patient-reported utilization by a unit cost. RESULTS: A total of 367 participants were followed for a mean of 15.3 quarters (range 1-26). Medication accounted for most (61.8%) of the $26,832 annual cost. Cost averaged $4147 per quarter for ART, $1981 for inpatient care, $580 for outpatient care, and $346 for other medications. Cost for inpatient stays, outpatient visits, and other medications was 171% higher (P <.01) and cost of ART was 32% lower (P <.01) when cluster of differentiation 4 (CD4) count was <50 cells/µL compared with periods when CD4 count was >200 cells/µL. Some baseline characteristics, including low CD4 count, high viral load, and HIV from injection drug use with hepatitis C coinfection, had a sustained effect on cost. CONCLUSIONS: The association between health status and cost depended on the type of care. Indicators of poor health were associated with higher inpatient and concomitant medication costs and lower cost for ART medication. Although ART has supplanted hospitalization as the most important cost in HIV care, some patients continue to incur high hospitalization costs in periods when they are using less ART. The cost of interventions to improve the use of ART might be offset by the reduction of other costs.

Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.

Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care.

The economic burden of tuberculosis care for patients and households in Africa: a systematic review.

OBJECTIVES: To summarise the state of knowledge on the economic impact and consequences of tuberculosis (TB) diagnosis and treatment for patients/households in Africa, and to highlight any weaknesses in the work conducted to date. METHODS: We systematically searched for published articles in English between 1990 and June 2010 in eight databases and the World Health Organization (WHO) website. Broad search terms were used ('tuberculosis' OR 'tuberculosis/HIV' AND 'costs' AND 'Africa'). Only studies that reported any costs of TB care for patients/households were retained. All costs were converted to 2009 USD in accordance with WHO cost analysis guidelines. RESULTS: Overall, 11 articles from eight countries met the inclusion criteria. Only one study met all the quality criteria for a cost-of-illness study; most of the studies focused on urban populations, reported incomplete (pre-diagnostic/average) costs, and did not report coping costs. Mean patient pre-diagnostic costs varied between US$36 and US$196, corresponding to respectively 10.4% and 35% of their annual income. Average patient treatment costs ranged between US$3 and US$662, corresponding to 0.2-30% of their annual income. Pre-diagnostic household costs accounted for 13% and 18.8% of patients' annual household income, while total household treatment costs ranged between US$26 and US$662, accounting for 2.9-9.3% of annual household income; 18-61% of patients received financial assistance from outside their household to cope with the cost of TB care. CONCLUSION: The average patient's/household's pre-diagnostic costs for TB care were catastrophic. More properly designed studies are needed among different populations throughout Africa.