Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings

RATIONALE: A low cost point of care test (POCT) to diagnose hepatitis C virus (HCV) viremia could be a critical step toward HCV elimination. The aim of this study is to inform the limit of detection (LOD) for an affordable POC test. METHODS: This study analyzed a convenience sample of cross-sectional HCV testing data from reference laboratories and clinical research studies in 9 countries. Participants of all ages with quantified HCV viremia were included. We analyzed the distribution of HCV viral load for the first detectable HCV RNA available, and derived the clinical sensitivity for a POCT with an LOD of 3 log IU/mL. Bivariate and multivariate analyses were then performed to identify demographic and clinical characteristics associated with low-level viremia (< 3 log IU/mL). RESULTS: The dataset included 53,295 participants from Cambodia, Canada, Cameroon, Georgia, Indonesia, Malaysia, Pakistan, Thailand, and Vietnam. Log HCV RNA was normally distributed, and ≥ 3 log IU/mL corresponded with clinical sensitivity of 98%. Neither HIV co-infection nor cirrhosis were significantly associated with low-level viremia, whereas bivariate analyses showed increased odds of 2.47 (95% CI 2.04, 2.99) for low-level HCV RNA among those ≤ 30 years old compared to those > 30, and an OR of 1.17 (1.02, 1.34) among females compared to males. Stepwise multivariate regression found no significant confounding. CONCLUSION: In this global dataset, a POCT with a LOD of 3 log IU/mL would identify 98% of chronic HCV infections. The increase OR among those ≤ 30 years old year olds is likely explained by a greater frequency among younger persons of recent infection, where fluctuating viremia is well described. A POCT for HCV that could identify persons with 3 log IU/mL or greater would likely facilitate affordable product development and expand the reach of HCV testing in resource-limited settings.2019-03-17T00:00:00

Current Practices of Screening for Incident Hepatitis C Virus (HCV) Infection Among HIV-Infected, HCV-Uninfected Individuals in Primary Care

Background. Human immunodeficiency virus (HIV)-infected, hepatitis C virus (HCV)-uninfected patients are at risk for incident HCV infection, but little is known about screening practices for incident HCV among HIV-infected individuals in HIV primary care clinics

Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis.

BACKGROUND:Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS:We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS:In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS:The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance

Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis.

BACKGROUND:Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS:We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS:In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS:The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance

Prevalence of elevated liver transaminases and their relationship with alcohol use in people living with HIV on anti-retroviral therapy in Uganda.

BackgroundIsoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use.SettingThe Immune Suppression Syndrome Clinic of Mbarara, Uganda.MethodsWe defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI).ResultsAmong 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p&lt;0.01). In multivariable analyses, those currently using alcohol had higher odds of elevated transaminases compared to those abstaining (aOR 1.65, 95% CI 1.15-2.37) as did males compared to females (aOR 2.68, 95% CI 1.90-3.78).ConclusionsPre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus&nbsp;(HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL)&nbsp;±&nbsp;weight-based ribavirin for 12&nbsp;weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12&nbsp;weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54$1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of$1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population