Incidence and risk factors of nevirapine-associated skin rashes among HIV-infected patients with CD4 cell counts <250 cells/microL

The objective of the study was to determine cumulative incidence and risk factors of nevirapine (NVP)-associated rashes that lead to NVP discontinuation among HIV-infected patients with CD4 <250 cells/microL. A retrospective cohort study was conducted among antiretroviral-na?ve HIV-infected patients who had baseline CD4 <250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. There were 910 patients with a mean age of 35.4 years and 43% were women. Median CD4 cell count was 27 cells/microL and median HIV RNA was 5.5 log copies/mL. Cumulative incidences of rashes at 0.5, 1, 2, 3 and 6 months after ART were 3.7%, 6.2%, 8.1%, 8.5% and 8.5%, respectively. By Kaplan-Meier analysis, the higher baseline CD4 cell counts had a higher probability of NVP-associated rashes (log-rank test, P=0.041). By Cox regression analysis, higher baseline CD4 cell count was associated with a higher incidence of rashes (hazard ratio=1.244, 95% confidence interval=1.045-1.482, for every 50 cells/microL increment of baseline CD4 stratum). In conclusion, NVP-associated skin rashes that lead to NVP discontinuation are common among HIV-infected patients with baseline CD4 <250 cells/microL. Despite the low baseline in this population, the higher number of baseline CD4 cells is continuously associated with a higher risk for skin rashes.     

Impact of drug-resistant tuberculosis on the survival of HIV-infected patients.

OBJECTIVE: To determine the effect of drug-resistant tuberculosis (TB) on the survival of human immunodeficiency virus (HIV) infected patients in an area with a high prevalence of TB. DESIGN: Retrospective cohort study. RESULTS: Of 225 HIV-TB patients with a mean age of 35.8 years, 72.4% were male. The median CD4 cell count at TB diagnosis was 44 cells/mm3. Sixty per cent presented with extra-pulmonary TB (EPTB). Sixty-three (28%) patients were infected with Mycobacterium tuberculosis resistant to at least one drug; respectively 16.4%, 9.3%, 5.3% and 12.9% were resistant to isoniazid (INH), rifampicin (RMP), ethambutol and streptomycin, and 14 (6.2%) had multidrug-resistant TB (MDR-TB). During a median follow-up of 11.5 months, 4% died. From Kaplan-Meier analysis, INH resistance, RMP resistance and MDR-TB were associated with shorter survival (log-rank test, P < 0.005). Cox's proportional hazard model showed that MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1-64.9), not receiving antiretroviral therapy (ART) (HR 7.9; 95% CI 1.5-43.1) and EPTB (HR 5.1; 95% CI 1.9-25.9) were significant risk factors for death. CONCLUSION: MDR-TB and EPTB substantially reduce survival among patients co-infected with HIV and TB. Early detection and optimal treatment of MDR-TB are crucial. ART significantly prolongs survival and should be initiated in HIV-TB co-infected patients.     

CYP2B6 18492T→C Polymorphism Compromises Efavirenz Concentration in Coinfected HIV and Tuberculosis Patients Carrying CYP2B6 Haplotype *1/*1

Data regarding the effect of the CYP2B6 18492T→C polymorphism on plasma efavirenz concentrations and 96-week virologic responses in patients coinfected with HIV and tuberculosis (TB) are still unavailable. A total of 139 antiretroviral-naive HIV-infected adults with active TB were prospectively enrolled to receive efavirenz 600 mg-tenofovir 300 mg-lamivudine 300 mg. Eight single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped. Seven SNPs, including 64C→T, 499C→G, 516G→T, 785A→G, 1375A→G, 1459C→T, and 21563C→T, were included for CYP2B6 haplotype determination. The CYP2B6 18492T→C polymorphism was studied in 48 patients who carried haplotype *1/*1. At 12 and 24 weeks after antiretroviral therapy, plasma efavirenz concentrations at 12 h after dosing were measured. Plasma HIV RNA was monitored every 12 weeks for 96 weeks. Of 48 patients {body weight [mean ± standard deviation (SD)], 56 ± 10 kg}, 77% received a rifampin-containing anti-TB regimen. No drug resistance-associated mutation was detected at baseline. The frequencies of the wild type (18492TT) and the heterozygous (18492TC) and homozygous (18492CC) mutants of the CYP2B6 18492T→C polymorphism were 39%, 42%, and 19%, respectively. At 12 weeks, mean (±SD) efavirenz concentrations of patients who carried the 18492TT, 18492TC, and 18492CC mutants were 2.8 ± 1.6, 1.7 ± 0.9, and 1.4 ± 0.5 mg/liter, respectively (P = 0.005). At 24 weeks, the efavirenz concentrations of the corresponding groups were 2.4 ± 0.8, 1.7 ± 0.8, and 1.2 ± 0.4 mg/liter, respectively (P = 0.003). A low efavirenz concentration was independently associated with 18492T→C (β = −0.937, P = 0.004) and high body weight (β = −0.032, P = 0.046). At 96 weeks, 19%, 17%, and 28% of patients carrying the 18492TT, 18492TC, and 18492CC mutants, respectively, had plasma HIV RNA levels of >40 copies/ml and developed efavirenz-associated mutations (P = 0.254). In summary, the CYP2B6 18492T→C polymorphism compromises efavirenz concentrations in patients who carry CYP2B6 haplotype *1/*1 and are coinfected with HIV and tuberculosis.     

Persistent low-level viraemia and virological failure in HIV-1-infected patients treated with highly active antiretroviral therapy

OBJECTIVE: To assess the prognostic significance of persistent low-level viraemia (PLV, defined as persistent plasma viral loads of 51-1000 HIV-1 RNA copies/mL for at least 3 months) in patients who had achieved viral suppression on antiretroviral therapy (ART). METHODS: A retrospective cohort of HIV-infected patients who received ART, were followed-up for > or =12 months, made regular visits to the clinic during which blood tests were performed for an ultrasensitive HIV RNA assay every 3 months, and achieved viral loads <50 copies/mL were evaluated. Virological failure was defined as two consecutive viral load measurements >1000 copies/mL. RESULTS: Of 362 patients, 78 (27.5%) experienced PLV. The demographics of patients with and without PLV were similar. PLV occurred at a mean (+/-standard deviation) of 22.6+/-16.9 months after ART initiation and lasted for 6.4+/-3.4 months. During a median follow-up of 29.5 months, patients with PLV had a higher rate of virological failure (39.7% vs 9.2%; P < 0.001). The median time to failure was 68.4 months [95% confidence interval (CI) 37.0-99.7] for patients with PLV and >72 months for patients without PLV (log rank test, P < 0.001). By Cox regression, patients with PLV had a greater risk of virological failure [hazard ratio (HR) 3.8; 95% CI 2.2-6.4; P < 0.001]. Among patients with PLV, a PLV of >400 copies/mL (HR 3.3; 95% CI 1.5-7.1; P = 0.003) and a history of ART (HR 2.4; 95% CI 1.0-5.7; P = 0.042) predicted virological failure. CONCLUSIONS: PLV is associated with virological failure. Patients with a PLV >400 copies/mL and a history of ART experience are more likely to experience virological failure. Patients with PLV should be considered for treatment optimization and interventional studies.