Benefit of IPT plus ART was evident only in the first 6 months of care. These findings suggest that TST-guided IPT should be routinely provided for HIV-infected patients after initial entry into medical care.

ObjectiveTo compare virological and immunological responses to nevirapine (NVP)-based and efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens in antiretroviral-naïve patients with advanced HIV infection. MethodsA retrospective observational cohort study was conducted on antiretroviral-naïve HIV-infected patients whose pretreatment CD4 cell counts were less than 100 cells/mL or whose viral loads were greater than 100 000 HIV-1 RNA copies/mL. ResultsBaseline characteristics of patients in the NVP (n 5 24) and EFV (n 5 29) groups were not different. The proportion of patients with viral loads 4100 000 copies/mL was higher in the EFV group. The probability of virological success estimated by the Kaplan-Meier method showed that 3-and 6-month success rates were 30.8% [95% confidence interval (CI): 16.7-52.2%] and 63.1% (95% CI: 44.7-81.3%) for the NVP group. The corresponding values were 41.2% (95% CI: 25.8-61.0%) and 62.9% (95% CI: 45.7-80.1%) for the EFV-based group. The median success times of the two groups were about 4 and 3 months (P 5 0.678), respectively, for NVP and EFV. Cox's proportional hazard was used after adjusting for age, previous opportunistic infections (OIs), and viral load at baseline, and showed that patients who received the NVP-based regimen had about 25% [hazard ratio (HR) 5 0.75, 95% CI: 0.37-1.51] less chance of virological success than patients who received the EFV-based regimen (P 5 0.415). The median times to CD4 ! 100 cells/mL were 5.6 and 4.4 months for the NVP-and EFV-based regimens, respectively (log-rank test, P 5 0.144). ConclusionsNVP-and EFV-based HAART regimens as initial regimens in patients with advanced HIV infection are effective and comparable, in term of virological and immunological responses. However, further large-scale randomized controlled clinical trials in this group of patients with advanced HIV infection are needed. IntroductionHighly active antiretroviral therapy (HAART) is effective in reducing the plasma viral load and in prolonging AIDS-free survival, as shown in various studies [1][2][3]. Nevirapine (NVP) and efavirenz (EFV) are nonnucleoside reverse transcriptase inhibitors (NNRTI) which were approved by the Food and Drug Administration of the United States in the late 1990s to treat HIV infection [4][5][6]. In developing countries, the majority of HIV-infected patients who present to clinics are in an advanced stage of the disease [7,8]. Although the EFV-based regimen has been shown to be effective in patients with advanced infection [9][10][11] (2) were naïve to antiretroviral therapy, and (3) had a CD4 cell count o100 cells/ mL or a viral load (determined by PCR; Amplicor; Roche Diagnostics, Indianapolis, IN) ! 100 000 HIV-1 RNA copies/mL. Each eligible patient was followed up since receiving HAART until the end of the study, in August 2002, and (4) received a NVP-based or EFV-based HAART regimen. After receiving treatment, patients were followed up to assess their CD4 cell counts and viral loads every 3-4 months. Medical records w...

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Purpose of study: Polymorphisms of CYP2B6 are associated with altered activity of cytochrome P450 2B6 which has an effect on plasma efavirenz level. The data of these polymorphisms and their effect, particularly in HIV/TB co-infected patients, is still limited. Methods: A total of 150 HIV-infected Thai adults with active tuberculosis (TB) and receiving rifampicin-containing anti-TB regimen were prospectively enrolled to receive a once-daily regimen of efavirenz 600 mg/tenofovir/lamivudine. Nine single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped using real-time PCR-based allelic discrimination. At 12 weeks after ART, plasma efavirenz levels at 12 hours after dosing were measured by HPLC assay. Summary of results: Of all, the median (IQR) CD4 count was 44 (17–113) cells/mm3 and median (IQR) plasma HIV-1 RNA was 5.8 (5.4–6.3) log copies/mL. Eight (5.3%) patients discontinued efavirenz due to adverse events prior to measuring efavirenz level. Of 142 patients, the frequencies of wild type, heterozygous mutant, and homozygous mutant of each SNP were 64C>T (89%, 10%, 1%), 499C>G (99%, 1%, 0%), 516G>T (45%, 47%, 8%), 785A>G (36%, 54%, 10%), 1375A>G (100%, 0%, 0%), 1459C>T (97%, 3%, 0%), 3003C>T (29%, 44%, 27%), 18492T>C (55, 39%, 6%), and 21563C>T (38%, 57%, 5%). Median (IQR) plasma efavirenz level of 102 patients who were concurrently receiving efavirenz and rifampicin was 2.08 (1.33–3.51) mg/dL and those of 40 patients who did not received rifampicin was 2.72 (1.80–5.21) mg/dL. Of 102 patients, heterozygous/homozygous mutant vs. wild type of 5 SNPs associated with high mean efavirenz level were 516G>T (3.6 vs. 1.9 mg/dL, P<0.001), 785A>G (3.2 vs. 2.0 mg/dL, P=0.001), 3003C>T (4.0 vs. 2.4 mg/dL, P=0.012), 18492T>C (3.5 vs. 2.0, P<0.001), 21563C;>T (3.4 vs. 1.9 mg/dL, P<0.001). Three of 9 haplotypes identified, including *6/*6, *1/*6, and *4/*6, were associated with high efavirenz level. By multivariate analysis, factors associated with high efavirenz level included specific haplotype (P<0.001), low body weight (P=0.003), and receiving rifampicin (P=0.058). Conclusions: Particular SNPs and haplotype of CYP2B6, especially *6/*6, has the greatest impact on efavirenz level in HIV/TB co-infected Thai patients whereas low body weight and concurrent receiving rifampicin have lesser effects