We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.

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Background: An increase in tuberculosis (TB) incidence has been associated with human immunodeficiency virus (HIV). Aims: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART). Settings and Design: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. Materials and Methods: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ3 /4RH3) thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. Results: Of 498 patients with HIV and tuberculosis, 31 (6%) were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB) in 14 patients (45%) and Mycobacterium tuberculosis was isolated in 21 (68%). The mean CD4 cell count was 129 ± 125 cells/mm3. Twenty-five patients were declared cured at the end of treatment (81%) while one (3%) died and five (16%) failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20). None of the patients received antiretroviral therapy. Conclusions: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.

Background and Objectives:A variety of demographic factors, sex, and degree of immunosuppression can influence antiretroviral drug concentrations. The authors studied the influence of immune status, sex, and body mass index (BMI) on the steady-state pharmacokinetics of nevirapine delivered as a fixed-dose combination in HIV-1-infected patients in India. Methods: Twenty-six HIV-1-infected adult patients undergoing treatment with nevirapine-based highly active antiretroviral therapy regimens participated in the study. Pharmacokinetic variables were compared between patients divided based on CD4 cell counts, sex, and BMI. Results: Patients with higher BMI had lower peak and trough concentration and exposure of nevirapine than those with lower BMI; none of the differences in the pharmacokinetic variables of nevirapine between the various patient groups was statistically significant. Conclusions: Patients' immune status, sex, or BMI had no impact on the pharmacokinetics of nevirapine. Plasma nevirapine concentrations were maintained within the therapeutic range of the drug in the majority of the patients.Keywords: pharmacokinetics; nevirapine; India; immune status; sex; BMI Access to antiretroviral drugs for HIV-1-infected patients in developing countries is a global public health priority. The World Health Organization currently recommends first-line therapy with 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-NRTI (NNRTI)⎯a combination with good efficacy, tolerability, simplicity, and low cost. 1 Generic fixed-dose combinations (FDCs) of such regimens are widely regarded as crucial for scaling up AIDS treatment in developing countries. Two triple-drug combinations consisting of nevirapine and lamivudine with either stavudine or zidovudine as the third agent are available as FDCs in the developing world. A vast majority of HIV-infected patients in India receive nevirapine-based highly active antiretroviral therapy (HAART), the common co-drugs being lamivudine and stavudine. 2 A few studies have reported the effectiveness and safety of generic FDCs for treatment of HIV-1-infected adults. [2][3][4][5] It has been suggested that a variety of demographic factors such as age, body size, and weight can influence antiretroviral drug concentrations. 6 Sex-based differences in the pharmacokinetics of nevirapine have also been observed. 7 Keating et al reported that malabsorption correlates significantly with the degree of immunosuppression. 8 We undertook a study to obtain information on the pharmacokinetics of nevirapine in HIV-infected patients on treatment with FDCs in India, as well as the influence of immunological status, sex, and body mass index (BMI) on the pharmacokinetics of these drugs, as very limited information is available on this aspect. Methods PatientsThe study participants were composed of HIV-infected patients of ethnic Indian origin who were participating in a controlled clinical trial and were being followed

Natural killer (NK) cells control Mycobacterium tuberculosis infection mainly through secreted cytokines. Cytokine dysregulation among HIV may cause rapid disease progression. Our objective was to examine whether impaired production of innate cytokines are responsible for cytokine dysregulation during HIV infection. The study included 30 subjects each of normal healthy subjects (NHS), pulmonary tuberculosis patients (TB), HIV-infected individuals (HIV), and HIV-TB co-infected patients (HIV-TB). Intracellular cytokine staining method was used to enumerate the cytokine-positive NK cells. Unlike NHS (100%), only 27% of HIV-TB and 57% of HIV infected patients have detectable plasma interleukin (IL)-15 levels that signify impaired rather than decreased IL-15 production. Basal type 1 cytokine (IL-2, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha])-secreting NK cells (NK1 cytokines) were decreased significantly (P < 0.05) in TB, HIV, and HIV-TB, when compared with NHS. Stimulation with M. tuberculosis H37Rv enhanced the NK1 cytokines in NHS (P < 0.05), but not in other groups. With IL-15+IL-12 stimulation, we found increased NK1 cytokines (IL-2 and IFN-gamma) in HIV (P < 0.05), but not in HIV-TB, when compared to unstimulated condition. Supplementing IL-15+IL-12 has potential in improving the frequency of NK1 cytokines for HIV, but not HIV-TB, suggesting that TB influences cytokine response during HIV infection.