Showing papers by "Soumya Swaminathan published in 2006"

Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration.

Abstract: 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.

Hepatitis B or hepatitis C co-infection in individuals infected with human immunodeficiency virus and effect of anti-tuberculosis drugs on liver function

Abstract: Background: Tuberculosis (TB) and hepatitis are the two common co-infections in patients infected with human immunodeficiency virus (HIV). Anti-tuberculosis treatment (ATT) may have an effect on the liver enzymes in these co-infected HIV patients. Aims: To determine the prevalence of Hepatitis B and C virus coinfection in HIV infected patients in Tamilnadu and assess effects of anti-tuberculosis drugs on their liver function. Settings: HIV positive subjects referred to the Tuberculosis Research Centre, Chennai Materials and Methods: All HIV infected patients referred to the Tuberculosis Research centre, from March 2000 to May 2004, were screened for Hepatitis B surface antigen (HBsAg) & Hepatitis C virus (HCV) antibodies by enzyme linked immunoabsorbent assay (ELISA). HIV infection was confirmed using two rapid tests and one ELISA.Patients were given either short- course anti-tuberculosis treatment or preventive therapy for tuberculosis, depending on the presence or absence of active TB, if their baseline liver functions were within normal limits. None of these patients were on antiretroviral therapy during the study period. Statistical Analysis: Paired t-test was used to find the significance between baseline and end of treatment liver enzymes levels, while logistic regression was done for assessing various associations. Results: Of the 951 HIV-infected patients, 61 patients (6.4%) were HBsAg positive, 20 (2.1%) had demonstrable anti HCV antibodies in their blood. Serial estimation of liver enzymes in 140 HIV patients (81 being co-infected with either HBV or HCV) showed that 95% did not develop any liver toxicity while they were on anti-tuberculosis treatment or prophylaxis. Conclusions: The prevalence of hepatitis B and C coinfection was fairly high in this largely heterosexually infected population supporting the use of more careful screening for these viruses in HIV positive persons in this region. Anti-tuberculosis therapy as well as TB preventive therapy can be safely employed in HIV and hepatitis coinfected patients, if baseline liver function tests are within normal limits.

Association of human leukocyte antigen-A11 with resistance and B40 and DR2 with susceptibility to HIV-1 infection in south India.

Abstract: To the Editor: HIV-1 and Mycobacterium tuberculosis are the two leading infectious agents causing death worldwide. Increasing morbidity and mortality among HIV1–infected individuals in areas where M tuberculosis is endemic are attributable to tuberculosis (TB) to a large extent. Because of the pivotal role of the human leukocyte antigen (HLA) genes and gene products in controlling the immune response, the association between HLA genes and infectious diseases has been extensively studied. Various studies have identified an association between HLA genes (class I and class II) and HIV-1 infection and disease progression. Most of the studies carried out in whites and Africans have indicated that HLA-B27 and HLA-B57 are associated with a slow progression to AIDS and that HLA-B35 is associated with rapid disease progression. Further, studies carried out in Asian populations have linked the development of pulmonary TB with the HLA class II region, specifically HLA-DR2. In the context of HIV-1 and M tuberculosis coinfection, there is a dearth of reports on the HLA genes predisposing to development of TB in HIV-1–infected individuals. In the present study, we have explored the possible association between HLA (-A, -B, and -DR loci) and HIV-1 with and without TB in a group of south Indian patients. The study population comprised 151 HIV-1–seropositive subjects without TB (HIVTB ) (64 male, mean age 6 SD: 32.1 6 6.9 years; 87 female, mean age 6 SD: 28.6 6 6.7 years) and 108 HIV-1–seropositive subjects with active TB (HIVTB) (78 male, mean age 6 SD: 35.3 6 5.7 years; 30 female, mean age 6 SD: 31.0 6 7.1 years) recruited from the HIVand TB clinics of the Tuberculosis Research Center, Chennai, India, and 170 healthy controls from the same ethnic background (104 male, mean age 6 SD: 33.0 6 8.0 years; 66 female, mean age 6 SD: 32.9 6 8.8 years). The diagnosis of TB was based on sputum smear examination for acid-fast bacilli and confirmed by culture for M tuberculosis. HIV-1 was diagnosed using 2 rapid tests (HIV tridot, J. Mitra, India; CombAids, Span Diagnostics, India), and a positive result was confirmed by a third test (Western blot, J. Mitra, India). The present study was approved by the institutional ethical committee, and written informed consent was obtained from all the participants of the study. The patients and controls represented the same ethnic group of the south Indian population from the state of Tamilnadu. HLA-A and HLA-B typing was carried out using a 2-stage microlymphocytotoxicity test. HLA-DR genotyping was studied by polymerase chain reaction and sequence-specific oligo probe method. The frequencies of HLA antigens of patients and controls were compared using the x test. P values with Yates correction and odds ratios were calculated using the Statcalc program (Epi Info version 6.04, Centers for Disease Control and Prevention, Atlanta, GA, July 1996) with 95% confidence intervals. The P values were further corrected by the Bonferroni inequality method, wherein the P values obtained were multiplied with the number of antigens studied in each locus and expressed as P-corrected (Pc) values. Among the antigens studied, a decreased frequency of HLA-A11, HLAB17, HLA-B35, and HLA-DR7 and an increased frequency of HLA-A19 (32 + 33), HLA-B18, HLA-B40, and HLADR2 were observed in the HIVTB and HIVTB groups compared with healthy controls. The difference attained statistical significance only in the case of HLA-A11 (overall HIV-1–infected vs. controls: Pc = 0.00066), HLA-B40 (Pc = 0.019), and HLA-DR2 (Pc = 0.037). When the HIV-1TB and HIV1TB groups were compared, HLA-A11 alone showed marginal significance (P = 0.0179, Pc = 0.196; Table 1). In the present study, an increased prevalence of HLA-B40 and HLA-DR2 antigens was observed in HIV-1–infected and HIV-1 and M tuberculosis–coinfected individuals, suggesting their association with susceptibility to HIV-1 and HIV-1 and M tuberculosis coinfection. On the other hand, a decreased prevalence of HLAA11 was observed in both HIV patient groups. This suggests that the presence of A11 may be associated with protection against HIV-1 and, more strongly, against HIV-1 and M tuberculosis coinfection. Moreover, our study also revealed that HLA-A11 is not associated with any protection against TB infection (HIV TB patients: HLA-A11 frequency of 26.5%; data not shown). This suggests that strong protection observed is against HIV-1 and M tuberculosis coinfection. Because this is a cross-sectional study, further follow-up studies may delineate the role of HLA-A11 in protection against HIV-1 infection and HIV-1 and M tuberculosis coinfection. A higher frequency of HLA-A11 was observed among highly exposed persistently seronegative women of Thailand, which suggests the protective role of HLA-A11 against HIV-1 infection. Another recent report also corroborates the protective role of HLAA11, wherein it describes that the immune system of individuals expressing HLAA11 frequently elicits CD8 T-cell responses against a common HLAA11–restricted escape variant epitope in HIV-1 gag. A number of potential mechanisms have been put forward to explain the association of HLA-A11 with resistance to HIV-1 infection and HIV-1 and M tuberculosis coinfection. HLAA11 is one of the most common class I alleles in the world, ranging from 4% to 33% depending on the particular ethnic background, and it is highly prevalent in Southeast Asia. A*1101 is the most prevalent variant of A11 and is known preferably to bind peptide residues with small or aliphatic side chains at position 2 and with positively charged side chains at the C-terminus position. The structural features of the A*1101 binding groove permit peptides to adopt a backbone conformation with two bulges separated by a secondary anchor residue. This may allow for binding of unrestricted specificity of viral peptides of various

A pilot study on willingness to participate in future preventive HIV vaccine trials.

Abstract: Background & objectives: In India, phase-I human clinical trials for a preventive HIV vaccine are being conducted at Pune and Chennai Centres. In order to find out the willingness of populations at risk to participate in future preventive HIV vaccine trials (HIVVTs) and to assess the factors that enhance or deter them from participation, a study was conducted at Chennai and Madurai in Tamil Nadu. Methods: This cross-sectional study was conducted among transport workers, people attending sexually transmitted infection clinics, injection drug users, men having sex with men, women in sex industry and a representative sample of monogamous married women, by employing measurement scales. A structured questionnaire on knowledge and attitudes about the HIV vaccine was used to measure the participants’ knowledge and attitudes about HIV vaccine and HIVVTs. Results: Of the 112 participants, 67 (60%) were men. Mean age of the respondents was 32 yr; 68 per cent were high school educated. Majority of respondents were willing to participate in a future HIVVT and the reasons were altruism, protection from HIV, and support for the researchers. Major concerns were vaccine efficacy, side effects of the vaccine and the impact of a HIV vaccine on the participants’ lives. Majority (85%) agreed that sex without condom would not be safe despite the availability of an HIV vaccine. Interpretation & conclusion: It is likely that high-risk volunteers will be willing to enroll in HIVVTs. Barriers and concerns should be dealt with carefully by providing correct information. Also there is a need for more education to ensure participants’ understanding of key concepts of HIV vaccine trial.

Can Urine Lamivudine Be Used to Monitor Antiretroviral Treatment Adherence

Abstract: Patient adherence to treatment is an important factor in the effectiveness of antiretroviral regimens. Adherence to treatment could be monitored by estimation of antiretroviral drugs in biological fluids. We aimed to obtain information on the quantity and duration of excretion of lamivudine in urine following oral administration of a single dose of 300 mg and to assess its suitability for adherence monitoring purposes. Spot urine samples were collected before dosing and at 4, 8, 12, 24, 28, 32, 48, 72, and 96 hours post dosing from 10 healthy subjects, and lamivudine was estimated by high-pressure liquid chromatography (HPLC). Lamivudine values were expressed as a ratio of urine creatinine. About 91% of the ingested drug was excreted by 24 hours, and the concentration thereafter in urine was very negligible. A lamivudine value of 0.035 mg/mg creatinine or less at 48 hours is suggestive of a missed dose in the last 24 hours. The study findings showed that estimation of urine lamivudine in spot specimens could be useful in monitoring patient adherence to antiretroviral treatment. However, this needs to be confirmed on a larger sample size and among patients on once-daily and twice-daily treatment regimens.

Immune reconstitution syndrome in a child with TB and HIV.

Abstract: Immune reconstitution syndrome (IRS) is the transient worsening or appearance of new signs, symptoms, or radiological manifestation of an opportunistic infection occurring after the initiation of Highly active antiretroviral therapy (HAART) and is not due to treatment failure or new infection. We describe a case of a HIV infected child with tubercular (mediastinal) lymphadenitis with worsening of clinical and radiological features on starting HAART.

Antiretroviral therapy and TB.

Abstract: With the expansion and convergence of the HIV and TB epidemics worldwide, clinicians will increasingly will be called to manage and treat co-infected patients. TB and HIV medications have overlapping and additive toxicities that can complicate therapy. Additional clinical challenges include choice of optimal first and second line antiretroviral therapy, appropriate timing of antiretroviral initiation, management of immune reconstitution disease, and TB diagnosed after initiation of HIV therapy. Despite the complexities presented by co-infection, many programmes have integrated care and are successfully treating patients with both HIV and TB.

Urine nevirapine as a predictor of antiretroviral adherence.

Abstract: Results: All the urine samples collected from patients undergoing treatment with NVP-containing regimens at different time points after drug administration tested positive for NVP. Thirteen out of 14 samples from patients not on NVP yielded a negative result. The drug was detected in the urine of healthy volunteers up to 9 days. The urinary excretion of NVP was prolonged in females than in males. Interpretation & conclusion: In view of its long half-life, NVP gets excreted in urine for a long period of time. Hence, testing spot urine samples for NVP may not be a useful measure to monitor patient adherence to treatment.