HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai patients

<p>Abstract</p> <p>Background</p> <p>A high incidence of rash has been reported in HIV-1 patients who received the anti-retroviral drug nevirapine. In addition, several studies have suggested that polymorphisms of human leukocyte antigen (<it>HLA</it>) genes may play important roles in nevirapine-induced rash. The aim of the present study was to evaluate the effects of different <it>HLA-C </it>alleles on rash associated with nevirapine in patients who started highly active anti-retroviral therapy (HAART) containing nevirapine in Thailand.</p> <p>Results</p> <p>A case-control study was carried out involving HIV-1 patients under treatment at Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand between March 2007 and March 2008. The study included all HIV/AIDS patients being treated with nevirapine-containing regimens. The study population comprised 287 HIV/AIDS patients of whom 248 were nevirapine-tolerant and 39 developed rash after nevirapine treatment. From the nevirapine-tolerant patients, 60 were selected as the control group on the basis of age, sex, and therapy history matched for nevirapine-induced rash cases. We observed significantly more <it>HLA-Cw*04 </it>alleles in nevirapine-induced rash cases than in nevirapine-tolerant group, with frequencies of 20.51% and 7.50%, respectively (P = 0.009). There were no significant differences between the rash and tolerant groups for other <it>HLA-C </it>alleles except for <it>HLA-Cw*03 </it>(P = 0.015).</p> <p>Conclusion</p> <p>This study suggests that <it>HLA-Cw*04 </it>is associated with rash in nevirapine treated Thais. Future screening of patients' <it>HLA </it>may reduce the number of nevirapine-induced rash cases, and patients with alleles associated with nevirapine-induced rash should be started on anti-retroviral therapy without nevirapine.</p

Durability of Stavudine, Lamivudine and Nevirapine among Advanced HIV-1 Infected Patients with/without Prior Co-administration of Rifampicin: A 144-week Prospective Study

<p>Abstract</p> <p>Background</p> <p>To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings.</p> <p>Methods</p> <p>A prospective cohort study was conducted among 140 antiretroviral-naïve patients who were enrolled to initiate d4T, 3TC and NVP between November 2004 and March 2005. The objectives were to determine immunological and virological responses after 144 weeks of antiretroviral therapy. Seventy patients with tuberculosis also received rifampicin during the early period of antiviral treatment (TB group).</p> <p>Results</p> <p>Of all, median (IQR) baseline CD4 cell count was 31 (14–79) cells/mm³; median (IQR) baseline HIV-1 RNA was 433,500 (169,000–750,000) copies/mL. The average body weight was 55 kilograms. By intention-to-treat analysis at 144 weeks, the overall percentage of patients who achieved plasma HIV-1 RNA <50 copies/mL was 59.3% (83/140). In subgroup analysis, 61.4% (43/70) patients in TB group and 57.1% (40/70) patients in control group achieved plasma HIV-1 RNA <50 copies/mL (RR = 1.194, 95%CI = 0.608–2.346, <it>P </it>= 0.731). Eight (5.8%) patients discontinued d4T due to neuropathy and/or symptomatic lactic acidosis.</p> <p>Conclusion</p> <p>The overall durability and efficacy of antiviral response of d4T, 3TC and NVP are satisfied and they are not different between HIV-1 infected patients with and without co-administration of rifampicin due to tuberculosis. However, stavudine-related adverse effects are concerns.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00703898</p

Viral hepatitis and HIV-associated tuberculosis: Risk factors and TB treatment outcomes in Thailand

<p>Abstract</p> <p>Background</p> <p>The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients.</p> <p>Methods</p> <p>Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines.</p> <p>Results</p> <p>Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2) and living in Bangkok (AOR, 15.8; CI, 9.4–26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker.</p> <p>Conclusion</p> <p>Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were common and strongly associated with known behavioral risk factors. Viral hepatitis infection markers were not strongly associated with death or the development of clinical hepatitis during TB treatment.</p

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy

HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS) as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children

Safety and efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine antiretroviral therapy between HIV-infected patients with baseline CD4 <50 versus CD4 ≥ 50 cells/mm³

<p>Abstract</p> <p>Background</p> <p>Antiretroviral therapy (ART) with a generic fixed-dose combination (FDC) of stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) is widely used in developing countries. The clinical data of this FDC among very advanced HIV-infected patients is limited.</p> <p>Methods</p> <p>A retrospective cohort study was conducted among ART-naïve HIV-infected patients who were initiated a generic FDC of d4T/3TC/NVP between May 2004 and October 2005. Patients were categorized into 2 groups according to the baseline CD4 (group A: <50 cell/mm³and group B: ≥ 50 cell/mm³).</p> <p>Results</p> <p>There were 204 patients with a mean ± SD age of 37.1 ± 8.9 years, 120 (58.8%) in group A and 84 (41.2%) in group B. Median (IQR) CD4 cell count was 6 (16–29) cells/mm³in group A and 139 (92–198) cells/mm³in group B. Intention-to-treat analysis at 48 weeks, 71.7% (86/120) of group A and 75.0% (63/84) of group B achieved plasma HIV RNA <50 copies/ml (<it>P </it>= 0.633). On-treatment analysis, 90.5% (87/96) in group A and 96.9% (63/65) in group B achieved plasma HIV RNA <50 copies/ml (<it>P </it>= 0.206). At 12, 24, 36 and 48 weeks of ART, mean CD4 were 98, 142, 176 and 201 cells/mm³in group A and 247, 301, 336 and 367 cells/mm³in group B, respectively. There were no differences of probabilities to achieve HIV RNA <50 copies/ml (<it>P </it>= 0.947) and CD4 increment at 48 weeks between the two groups (<it>P </it>= 0.870). Seven (9.6%) patients in group A and 4 (8.5%) patients in group B developed skin reactions grade II or III (<it>P </it>= 1.000). ALT at 12 weeks was not different from that at baseline in both groups (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Initiation of FDC of d4T/3TC/NVP in HIV-infected patients with CD4 <50 and ≥ 50 cells/mm³has no different outcomes in terms of safety and efficacy. FDC of d4T/3TC/NVP can be effectively used in advance HIV-infected patients with CD4 <50 cells/mm³.</p