Pegylated-interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remain unclear. We aimed to measure sustained ...virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany, and the United States. Individuals with acute or early chronic HCV who commenced pegylated-interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated-interferon n=161; pegylated-interferon/ribavirin n=76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen percent (n=38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention-to-treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85–0.99, p=0.033),
IFNL4
genotype (adjusted OR 2.27, 95%CI 1.13–4.56, p=0.021), baseline HCV RNA <400,000 IU/ml (aOR 2.06, 95%CI 1.03–4.12, p=0.041) and age ≥40yrs (versus <30: aOR 2.92, 95%CI 1.31–6.49, p=0.009), with no difference by drug regimen, HCV genotype, symptomatic infection, or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection,
IFNL4
genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision making.
INH preventive therapy (IPT) has been shown in several randomized controlled trials to reduce the risk of developing active TB in tuberculin skin test (TST) or purified protein derivative (PPD) ...positive HIV infected individuals. Detection of latent tuberculosis by TST and determination of factors associated with the PPD positivity in HIV-infected persons are important for the targeting of chemoprophylaxis. Six hundred asymptomatic and early symptomatic HIV-infected subjects attending the AIDS Clinic of the Chulalongkorn University Hospital, Bangkok, Thailand were enrolled in two randomized clinical trials of chemoprophylaxis against TB from December 1994 to December 1996. The availability of baseline characteristics, including TST reactivity, among these participants enabled a cross-sectional analysis of factors associated with PPD positivity. The results showed that 117 (19.5%) were PPD positive and 483 (80.5%) were PPD negative with ages 18-65 years (median 29 years). HIV exposure category was 46.2%, 34.5%, and 6.7% for heterosexual contact, commercial sex work, and homosexual and bisexual male contact respectively. The median CD4 cell count was 315/mm3 (range, 5-1,074/mm3). HIV exposure category and CD4 cell count were significantly associated with PPD status. Homosexual/bisexual contact had 3 times higher risk of PPD positivity than heterosexual contact (adjusted OR=2.9; 95% CI, 1.4-6.1) and risk of PPD positivity was higher among patients with CD4 cell counts of 200-500/ mm3 (adjusted OR=1.8; 95% CI, 1.0-3.1) and above 500/mm3 (adjusted OR=3.4; 95% CI, 1.7-6.7) when compared to patients with CD4 cell counts of less than 200/mm3. The HIV-infected persons in Bangkok with homosexual/bisexual contact are at higher risk for latent TB. Population-based tuberculin screening without accompanying HIV testing cannot be used to estimate the prevalence of actual latent TB in a population where HIV infection is widespread, such as in Thailand.
Background and Aim: Pegylated interferon (PEG-IFN) treatment for hepatitis C virus (HCV) infection has neuropsychiatric side effects. Data on the effect of HCV treatment on mental health among ...injecting drug users (IDUs) are limited. We assessed mental health during treatment of recently acquired HCV, within a predominantly IDU population. Methods: Participants with HCV received PEG-IFN- alpha -2a (180 mu g/week) for 24weeks; HCV/HIV received PEG-IFN with ribavirin. Depression was assessed using the Mini-International Neuropsychiatric Interview (MINI). Logistic regression was used to identify factors associated with depression at enrolment and during treatment. Also, the effect of depression prior to and during treatment on sustained virological response (SVR) was assessed. Results: Of 163 participants, 111 received treatment (HCV, n=74; HCV/HIV, n=37), with 76% ever reporting IDU. At enrolment, 16% had depression (n=25). In adjusted analysis, depression at enrolment occurred less often in participants full-/part-time employed (adjusted odds ratio AOR 0.23; 95% confidence interval CI: 0.06, 0.82, P=0.023) and more often in recent IDUs (AOR 3.04; 95% CI: 1.19, 7.72, P=0.019). During treatment, 35% (n=31) developed new-onset depression. In adjusted analysis, poorer social functioning (higher score) was associated with new-onset depression (score less than or equal to 9 vs score greater than or equal to 17; OR 5.69; 95% CI: 1.61, 20.14, P=0.007). SVR was similar among participants with and without depression at enrolment (60% vs 61%, P=0.951) and in those with and without new-onset depression (74% vs 63%, P=0.293). Conclusions: Although depression at enrolment and during treatment was common among participants with recent HCV, neither influenced SVR. Participants with poor social functioning may be most at risk of developing depression during HCV therapy.
To examine the influence of country/region of birth on spectrum of AIDS-defining illness.
National surveillance data for 4,629 adolescents and adults diagnosed with AIDS from 1992 through 1998 were ...analyzed. Country of birth was grouped into five broad categories (Australia, other predominantly industrialized country regions, sub-Saharan Africa, Asia-Pacific, and other regions with predominantly developing countries). Proportions of AIDS-defining illnesses were calculated and compared by country/region of birth. Role of country/region of birth in the distribution of AIDS-defining illnesses was further assessed using logistic models.
Of the 4,488 (97.0%) AIDS cases with country of birth recorded, 1,120 (25.0%) were born outside Australia. In multivariate analyzes, AIDS cases born in sub-Saharan Africa had an increased risk of tuberculosis (odds ratio OR, 18.7; confidence interval CI, 9.2-38.2) and cryptococcosis (OR, 2.4; CI, 1.1-5.4), but a decreased risk of esophageal candidiasis (OR, 0.3; 0.1-0.8) and Pneumocystis carinii pneumonia (OR, 0.5; 0.3-0.9) compared with AIDS cases born in Australia. Tuberculosis risk was also elevated among AIDS cases born in Asia-Pacific (OR, 9.6; 5.3-17.5) and other developing country regions (OR, 3.1; 0.9-10.4). Risk of AIDS-defining illnesses was similar for AIDS patients born in Australia and other industrialized country regions. Country of birth had no influence on risk of cytomegalovirus (CMV)-related disease and Mycobacterium avium complex (MAC) infection. Differential AIDS-defining illness risk was more pronounced among AIDS patients born in developing countries who had resided in Australia for less time.
Differential risk by country/region of birth for some AIDS-defining illnesses, especially among more recent arrivals from developing countries, suggests that environmental microbial habitats are important determinants of opportunistic infection risk. Similar risk of CMV disease and MAC infection is consistent with the ubiquitous nature of these microbial agents and suggests that previously reported low prevalence from developing countries may reflect poor diagnostic capacity rather than level of risk.
Polymorphisms in the
IL28B
gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of
IL28B
in spontaneous and ...treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in
IL28B
, were assessed. Among 163 participants, 132 were untreated (n=52) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=80). Spontaneous clearance was observed in 23% (30 of 132). In Cox proportional hazards analysis (without
IL28B
), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (AHR 2.86, 95% CI, 1.24, 6.59,
P
=0.014). Among participants with
IL28B
genotyping (n=102/163 overall and 79/132 for spontaneous clearance population), rs8099917 TT homozygosity (vs GT/GG) was the only factor independently predicting time to spontaneous clearance (AHR 3.78, 95% CI, 1.04, 13.76,
P
=0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%,
P
=0.047). Among participants adherent to treatment and had
IL28B
genotyping (n=54), SVR was similar among TT homozygotes (18/29, 62%) and those with GG/GT genotype (16/25, 64%,
P
=0.884).
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