Yanri Wijayanti Subronto

Detection of Active Tuberculosis Infection by T Cell Responses to Early-Secreted Antigenic Target 6-kDa Protein and Culture Filtrate Protein 10

The purified protein derivative (PPD) skin test has no predictive value for tuberculosis (TB) in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-vaccinated individuals because of cross-reactive responses to nonspecific constituents of PPD. T cell responses to early-secreted antigenic target 6-kDa protein (ESAT-6) and the newly identified culture filtrate protein 10 (CFP-10), 2 proteins specifically expressed by M. tuberculosis (MTB) but not by BCG strains, were evaluated. Most TB patients responded to ESAT-6 (92%) or CFP-10 (89%). A minority of BCG-vaccinated individuals responded to both ESAT-6 and CFP-10, their history being consistent with latent infection with MTB in the presence of protective immunity. No responses were found in PPD-negative controls. The sensitivity and specificity of the assay were 84% and 100%, respectively, at a cutoff of 300 pg of interferon-gamma/mL. These data indicate that ESAT-6 and CFP-10 are promising antigens for highly specific immunodiagnosis of TB, even in BCG-vaccinated individuals.

Clinical and virological characteristics of hepatitis B or C virus co-infection with HIV in Indonesian patients†

Hepatitis virus‐related liver disease increases substantially the mortality rate of patients with HIV on highly active antiretroviral therapy (HAART). Therefore, early diagnosis of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important. However, the prevalence of HBV and HCV infection in Indonesian patients infected with HIV is unknown. Therefore, this study examined the molecular and clinical characteristics of HBV and HCV in 126 patients infected with HIV, mostly on HAART, at Dr. Sardjito Hospital, Yogyakarta, Indonesia. The rates of triple infection, HIV/HCV co‐infection, HIV/HBV co‐infection, and mono‐infection were 4.8%, 34.1%, 3.2%, and 57.9%, respectively. Seven HCV genotypes were detected, with genotypes 1a, 1b, 1c, 3a, 3k, 4a, and 6n found in 23 (52%), 1 (2%), 4 (9%), 5 (11%), 7 (16%), 3 (6%), and 1 (2%) patients, respectively, indicating multiple modes of transmission. HBV‐DNA was detected in 2/10 patients with hepatitis B surface antigen; both patients were HAART naive. Univariate analysis revealed that male sex, higher education level, injection drug use, sexual contact, alanine aminotransferase ≥40 IU/L, and aspartate aminotransferase‐to‐platelet ratio index > 0.5 were associated with HCV co‐infection. In multivariate analysis, injection drug use (OR: 26.52; 95% CI: 3.52–199.54) and alanine aminotransferase ≥40 IU/L (OR: 6.36; 95% CI: 1.23–32.89) were independently associated with HCV co‐infection. HCV co‐infection was common among Indonesian patients infected with HIV, particularly among injecting drug users, and was a risk factor for disease progression of HIV. J. Med. Virol. 84:857–865, 2012.

GB virus C infection in Indonesian HIV‐positive patients

GB virus C (GBV‐C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV‐positive patients. However, the prevalence of GBV‐C in HIV‐positive individuals in Indonesia is unknown. Since GBV‐C is more prevalent in anti‐HCV positive patients than in anti‐HCV negative subjects, transmission of GBV‐C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV‐C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV‐C among HIV patients (n = 125, median age 31 years) based on the 5′UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV‐infected patients with and without HCV infection, respectively. GBV‐C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co‐infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV‐C among HIV‐positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6.

Interferon-γ Production in Response to M. Tuberculosis Antigens in Tb Patients in Indonesia

Tuberculosis (TB) accounts for 2-3 million deaths and 8 million new cases every year worldwide. Indonesia is one of the world’s TB-endemic countries with an estimated incidence of over 200 per 100,000 inhabitants. TB is the second leading cause of death and the third leading cause of morbidity in the country (Muharso, 2000).

Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients: a randomized cross-over trial

OBJECTIVES Concomitant food intake influences pharmacokinetics of first-line anti-TB drugs in healthy volunteers. However, in treatment-naive TB patients who are starting with drug treatment, data on the influence of food intake on the pharmacokinetics are absent. This study aimed to quantify the influence of food on the pharmacokinetics of isoniazid, rifampicin, ethambutol and pyrazinamide in TB patients starting anti-TB treatment. METHODS A prospective randomized cross-over pharmacokinetic study was conducted in treatment-naive adults with drug-susceptible TB. They received isoniazid, rifampicin and ethambutol intravenously and oral pyrazinamide on day 1, followed by oral administration of these drugs under fasted and fed conditions on two consecutive days. Primary outcome was the bioavailability while fasting and with concomitant food intake. This study was registered with clinicaltrials.gov identifier NCT02121314. RESULTS Twenty subjects completed the study protocol. Absolute bioavailability in the fasted state and the fed state was 93% and 78% for isoniazid, 87% and 71% for rifampicin and 87% and 82% for ethambutol. Food decreased absolute bioavailability of isoniazid and rifampicin by 15% and 16%, respectively. Pyrazinamide AUC0-24 was comparable for the fasted state (481 mg·h/L) and the fed state (468 mg·h/L). Food lowered the maximum concentrations of isoniazid, rifampicin and pyrazinamide by 42%, 22% and 10%, respectively. Time to maximum concentration was delayed for isoniazid, rifampicin and pyrazinamide. The pharmacokinetics of ethambutol were unaffected by food. CONCLUSIONS Food decreased absolute bioavailability and maximum concentration of isoniazid and rifampicin, but not of ethambutol or pyrazinamide, in treatment-naive TB patients. In patients prone to low drug exposure, this may further compromise treatment efficacy and increase the risk of acquired drug resistance.

Impacts of stigma on HIV risk for women who inject drugs in Java: A qualitative study

BACKGROUND People who inject drugs have experienced stigma around the world. Stigma has been found to have negative consequences for individuals in relation to health-service use, psychological wellbeing and physical health; and for populations in terms of health inequalities. Indonesia has experienced a rapid growth in injecting drug use and HIV and little is known about drivers of HIV risk among Indonesian women who inject drugs. The purpose of this paper is to describe and consider the multiple impacts of stigmatization of injecting drug use on injecting behaviors among women who inject drugs in Java. METHODS In-depth interviews were conducted with 19 women who inject drugs in Java. Mean age was 25 years, all but one was employed or at college. The interviewers were Indonesian women. RESULTS Significant stigma around womens drug use was reported from multiple sources in Java including family, friends and health services, resulting in feelings of shame. To avoid this stigma, most of the study participants hid their drug use. They lived away from family and had few friends outside their drug-injecting circle, resulting in isolation from mainstream society and harm-reduction services. Sharing of injecting equipment was restricted to a small, closed circle of trusted friends, thus limiting possible HIV transmission to a small number of injectors. CONCLUSIONS The stigmatization of drug use, particularly of drug use by women, in Indonesia appears to have contributed to significant shame, isolation from mainstream society and high rates of sharing injecting equipment with a small group of trusted friends (particularly the partner).

The cascade of HIV care among key populations in Indonesia: a prospective cohort study

BACKGROUND Indonesia has had low uptake of HIV testing and treatment. We did a study to estimate the cascade of HIV care in key populations and identify predictors of outcomes at key cascade steps. METHODS We used an observational cohort study design to recruit and follow up men who have sex with men (MSM), female sex workers, transgender women (known as waria in Indonesia), and people who inject drugs (PWID) diagnosed with HIV in four locations in Indonesia: Bali, Bandung, Jakarta, and Yogyakarta. Recruitment, baseline, and follow-up visits were done at collaborating clinical services, including both primary care sites and hospitals. Inclusion criteria for participants included identifying as a member of a key population, age 16 years or older, not previously tested positive for HIV, and HIV positivity at baseline. All participants were offered treatment as per national guidelines, with the addition of viral load testing and completion of study-specific forms. Estimates were calculated of proportions of participants linked to care, commencing treatment, adherent to treatment, and who achieved virological suppression. We used logistic regression to investigate characteristics associated with antiretroviral therapy (ART) initiation and viral suppression and Cox regression to identify factors associated with loss to follow-up. This study is registered with ClinicalTrials.gov, NCT03429842. FINDINGS Between Sept 15, 2015, and Sept 30, 2016, 831 individuals were enrolled in the study, comprising 637 (77%) MSM, 116 (14%) female sex workers, 27 (3%) waria, and 51 (6%) PWID. Of those enrolled, 703 (84·6%, 95% CI 82·1-87·1) were linked to HIV care and 606 (86·2%, 83·7-88·8) who were linked with care started ART. Among participants who started treatment, 457 (75·4%, 71·8-78·9) were retained in care, of whom 325 (71·1%, 66·7-75·2) had a viral load test about 6 months after enrolment, with 294 (90·5%, 86·7-93·4) of those tested (294 [35%, 32·1-38·7] of the original cohort) virally suppressed. 146 (24%) of 606 who started treatment were lost to follow-up. People who enrolled at sites that offered both testing and treatment had a higher likelihood of treatment initiation than those who enrolled at sites offering testing only (p<0·0001 by multivariate analysis), and participants who had been linked to care and had a high school or university education were significantly more likely to achieve viral suppression than those with a primary school or lower level of education (p≤0·029 by mulivariate analysis). INTERPRETATION HIV cascade data among key populations in Indonesia show very poor rates of retention in treatment and viral suppression. Site and individual characteristics associated with initiating and continuing treatment suggest an urgent need to develop and implement effective interventions to support patients in achieving viral suppression among all people with HIV. FUNDING Australian Government Department of Foreign Affairs and Trade, WHO, and Indonesian Government.