Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation.

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.

High rates of syphilis among STI patients are contributing to the spread of HIV-1 in India.

BACKGROUND: Recent syphilis outbreaks have raised concern regarding the potential enhancement of HIV transmission. The incidence of syphilis and its association with HIV-1 infection rates among a cohort of sexually transmitted infection (STI) clinic attendees was investigated. METHODS: 2732 HIV-1 seronegative patients attending three STI and one gynaecology clinic, were enrolled from 1993-2000 in an ongoing prospective cohort study of acute HIV-1 infection in Pune, India. At screening and quarterly follow up visits, participants underwent HIV-1 risk reduction counselling, risk behaviour assessment and HIV/STI screening that included testing for serological evidence of syphilis by RPR with TPHA confirmation. Patients with genital ulcers were screened with dark field microscopy. RESULTS: Among 2324 participants who were HIV-1 and RPR seronegative at baseline, 172 participants were found to have clinical or laboratory evidence of syphilis during follow up (5.4 per 100 person years, 95% CI 4.8 to 6.5 per 100 person years). Independent predictors of syphilis acquisition based on a Cox proportional hazards model included age less than 20 years, lack of formal education, earlier calendar year of follow up, and recent HIV-1 infection. Based on a median follow up time of 11 months, the incidence of HIV-1 was 5.8 per 100 person years (95% CI 5.0 to 6.6 per 100 person years). Using a Cox proportional hazards model to adjust for known HIV risk factors, the adjusted hazard ratio of HIV-1 infection associated with incident syphilis was 4.44 (95% CI 2.96 to 6.65; p<0.001). CONCLUSIONS: A high incidence rate of syphilis was observed among STI clinic attendees. The elevated risk of HIV-1 infection that was observed among participants with incident syphilis supports the hypothesis that syphilis enhances the sexual transmission of HIV-1 and highlights the importance of early diagnosis and treatment of syphilis.

Rate of hospitalization and inpatient care costs for HIV-1-infected patients in Pune, India.

BACKGROUND: The transition of human immunodeficiency virus (HIV) infection to acquired immune deficiency syndrome (AIDS) has begun in India, and an increase in AIDS-related hospitalizations and deaths is an anticipated challenge. We estimated the rates of hospitalization and inpatient care costs for HIV-1-infected patients. METHODS: Data were analysed on 381 HIV-1-infected persons enrolled in a HIV-1 discordant couples' cohort between September 2002 and March 2004. Inpatient care costs were extracted from select hospitals where the study patients were hospitalized and the average cost per hospitalization was calculated. RESULTS: A majority of the patients were in an advanced state of HIV-1 disease with the median CD4 counts being 207 cells/cmm (range: 4-1131 cells/cmm). In all, 63 participants who did not receive antiretroviral therapy required hospitalization, 53 due to HIV-1-related illnesses and the remaining 10 due to worsening of pre-existing conditions. The overall HIV-1-related hospitalization rate was 34.2 per 100 person-years (95% CI: 26.94-42.93). The median duration of HIV-1-related hospitalization was 10 days (range 2-48 days) and the median cost was Rs 17,464 (range: Rs 400-63,891). CONCLUSION: It is necessary to strengthen the inpatient care infrastructure and supporting diagnostic set-up, and work out economically optimized treatment algorithms for HIV-1-infected patients. Although this analysis does not cover all costs and may not be generalizable, these baseline data might be a useful reference while planning related studies accompanying the government-sponsored programme to roll out antiretroviral therapy to AIDS patients.

Low HIV-1 incidence among married serodiscordant couples in Pune, India.

Unlike commercial sex workers and patients attending sexually transmitted infection (STI) clinics, married couples are not typically targeted for HIV risk reduction programs in India. Thus, married partners of HIV-infected persons are at particularly high risk for HIV infection. Between September 2002 and November 2004, 457 HIV-1 sero-discordant, married couples were enrolled in a one-year prospective study of HIV transmission in Pune, India. The HIV incidence among uninfected partners was 1.22 per 100 person-years (95% CI 0.45-2.66), which is much lower than what has been previously reported among discordant couples in Africa. This may be due to higher rates of condom use, lower rates of STIs and higher CD4 T lymphocyte counts, among the Indian HIV sero-discordant couples.

Changing trends in clinical presentations in referred human immunodeficiency virus infected persons in Pune, India.

AIMS: To study profile and trends of clinical presentations among human immunodeficiency virus (HIV) infected individuals seen in a HIV Reference Clinic in Pune. METHODOLOGY: In a cross-sectional study, 3574 subjects were seen at a HIV Clinic in Pune from January 1997 to December 1999. Data on clinical presentation of 2801 (78.4%) HIV seropositive subjects were evaluated. RESULTS: Clinical conditions like oral thrush, tuberculosis, skin rash and sexually transmitted diseases showed decreasing trends during the three years study period (p=0.03, 0.02, < 0.01 and < 0.01, respectively). Conversely a significant increase in the number of asymptomatic HIV positive persons at the time of detection was observed over the same period (p < 0.01). CONCLUSION: Temporal change in the clinical presentations in the HIV positive persons referred to our clinic probably reflects increased awareness and a high index of suspicion among clinicians. Early diagnosis of HIV infection in asymptomatic phase might help the clinicians to make timely decisions on prescribing chemoprophylaxis for prevention of opportunistic infections and to take appropriate measures for prevention of secondary HIV transmission to the uninfected sex partners/spouses.

Relationship between clinical conditions and CD4 counts in HIV-infected persons in Pune, Maharashtra, India.

BACKGROUND: A decade after the detection of human immunodeficiency virus (HIV) infection in India, a steady increase in the number of patients with acquired immunodeficiency syndrome (AIDS) has been observed. The therapeutic options for patients with AIDS in developing countries include chemoprophylaxis and identifying and treating opportunistic infections. CD4 counts help in clinical monitoring and making decisions about initiating antiretroviral therapy or chemoprophylaxis. Flowcytometry is expensive and available only at specialized laboratories. Therefore, the possibility of using clinical indicators to predict low CD4 counts and disease progression needs to be explored. METHODS: This cross-sectional study was conducted among 137 HIV-infected persons investigated at an HIV reference centre in Pune. The study methods comprised pre-test counselling, informed consent, blood withdrawal and clinical evaluation. Serum samples were tested for HIV and CD4 counts were estimated on FACSort. RESULTS: Study participants commonly reported with oral candidiasis, herpes zoster, pulmonary tuberculosis, lymphadenopathy, weight loss, rash, diarrhoea and fever. CD4 counts were significantly lower among men, symptomatic patients and those with oral candidiasis, weight loss and multiple clinical conditions. The sensitivity of most of the clinical conditions was low, the specificity was high and the positive predictive value of oral candidiasis and weight loss for low CD4 counts was > 75%. CONCLUSION: The presence of oral candidiasis and weight loss were highly predictive of low CD4 counts and these can be considered as markers of HIV disease progression. Absence of clinical conditions was found to be a good predictor of high CD4 counts. Larger systematic natural history studies may help in identifying clinical conditions that could have a prognostic significance among HIV-infected people.