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

BACKGROUND: 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 (HLA) genes may play important roles in nevirapine-induced rash. The aim of the present study was to evaluate the effects of different HLA-C alleles on rash associated with nevirapine in patients who started highly active anti-retroviral therapy (HAART) containing nevirapine in Thailand. RESULTS: 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 HLA-Cw*04 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 HLA-C alleles except for HLA-Cw*03 (P = 0.015). CONCLUSION: This study suggests that HLA-Cw*04 is associated with rash in nevirapine treated Thais. Future screening of patients' HLA 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.

Effectiveness of boosted protease inhibitor-based regimens in HIV type 1-infected patients who experienced virological failure with NNRTI-based antiretroviral therapy in a resource-limited setting.

A number of patients have experienced treatment failure while receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART), particularly in resource-limited countries. The need remains for clinical data on protease inhibitor (PI)-based regimens in these patients. A retrospective cohort study was conducted among HIV-1-infected patients who had failed NNRTI-based regimens, were naive to protease inhibitors (PIs), and subsequently initiated a salvage PI-based regimen between January 2004 and December 2006. The study period ended on 30 December 2007. One hundred and forty patients received a single-boosted PI +/- optimized background regimen (OBR) and 64 received double-boosted PIs. The median (IQR) duration of follow-up was 19 (13-29) months. The overall virological failure rate at 24 months was 15.2%. No statistically significant difference was detected between the two regimen groups (single-boosted PI +/- OBR 16.4% vs. double-boosted PIs 12.5%, log rank p = 0.818). At the end of the study, the median (IQR) change in CD4 cell counts for patients in the double-boosted PI group was higher than for patients in the single-boosted PI +/- OBR group [149 (53-322) vs. 105 (23-199), respectively, p = 0.012]. Patients receiving double-boosted PI regimens displayed a higher frequency of hypertriglyceridemia than those patients who received a single boosted PI +/- OBR (31% vs. 11%, respectively, p = 0.001). Boosted PI-based regimens showed acceptable virological outcomes among patients who had failed NNRTI-based ART. In the subgroup analysis, patients who received double-boosted PIs demonstrated a superior immunological response but not better virological outcomes compared to the single-boosted PI +/- OBR group.

Haematological safety of perinatal zidovudine in pregnant HIV-1-infected women in Thailand: secondary analysis of a randomized trial.

OBJECTIVES: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women. DESIGN: Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis. SETTING: 27 hospitals in Thailand. PARTICIPANTS: 1,436 HIV-infected pregnant women in PHPT-1. INTERVENTION: Zidovudine prophylaxis initiation at 28 or 35 wk gestation. OUTCOME MEASURES: Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load. RESULTS: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts. CONCLUSION: Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

Screening HIV-infected women for cervical cancer in Thailand: findings from a demonstration project.

OBJECTIVES: Although cervical cancer is an AIDS-defining illness, few HIV-infected women are routinely screened for cervical cancer in Thailand. We screened HIV-infected women for cervical cancer as a component of HIV care and assessed high-risk human papillomavirus (HPV) and cervical cancer prevalence. METHODS: From July 2003 through February 2004, HIV-infected women attending either an infectious disease clinic or a sexually transmitted infection (STI) clinic in Bangkok were tested for high-risk HPV types by Hybrid Capture 2 and screened for cervical cancer by Pap test; those with abnormal cervical cytology were referred for diagnosis and treatment. RESULTS: Two hundred ten HIV-infected women at an infectious disease clinic (n = 150) and an STI clinic (n = 60) received cervical cancer screening. The high-risk HPV prevalence was 38.6% and the prevalence of abnormal cervical cytology was 20.4%. Abnormal cervical cytology and high-risk HPV detection were associated (P < 0.001). We received pathology reports for 23 (53.5%) of 43 women, including all those with a Pap test showing high-grade squamous intraepithelial lesions; the cervical cancer prevalence was 1.9% (4 of 210; 95% confidence interval, 0.5-4.8%). CONCLUSION: The estimated prevalence of high-risk HPV and cervical cancer among HIV-infected women in Thailand was high. This emphasizes the need to integrate cervical cancer screening into HIV care.