Eknath Naik

Effectiveness of generic fixed-dose combinations of highly active antiretroviral therapy for treatment of HIV infection in India.

Objective: To assess clinical and immunologic effectiveness and acute toxicity to nevirapine (NVP)-based fixed-dose combinations (FDCs) in antiretroviral-naive HIV-1-infected patients in India. Design: Observational study of patients initiated on NVP-based combination therapy delivered as FDCs. Methods: Antiretroviral-naive HIV-1-infected patients initiated on FDCs (zidovudine/lamivudine [3TC]/NVP or stavudine/3TC/NVP) were assessed clinically and with CD4 counts periodically. Adverse events to NVP were assessed clinically and by laboratory markers. Frequency and risk factors for development of adverse events and clinical outcomes were determined. Results: Of the 1291 patients started on therapy, 1253 completed a minimum of 3 months of follow-up. Rash and hepatitis were documented in 6.6% (95% confidence interval [CI]: 5.5-8.3) and 3.2% (95% CI: 2.3-4.8) of patients initiating therapy, respectively. There was significant improvement in CD4 counts over 2 years. Fourty-eight patients died, and 186 clinical events were documented in these patients. Tuberculosis was the most common cause of morbidity and mortality. Self-reported adherence was high. Conclusion: Fixed-dose formulations of NVP-based combination therapy are safe and produced durable clinical and immunologic benefit.

Rural Indian tribal communities: an emerging high-risk group for HIV/AIDS.

BackgroundRural Indian tribes are anthropologically distinct with unique cultures, traditions and practices. Over the years, displacement and rapid acculturation of this population has led to dramatic changes in their socio-cultural and value systems. Due to a poor health infrastructure, high levels of poverty and ignorance, these communities are highly vulnerable to various health problems, especially, communicable diseases including HIV/AIDS. Our study sought to assess knowledge, attitudes and practices regarding sexuality, and the risk factors associated with the spread of HIV/AIDS and STDs among these communities.MethodsA nested cross sectional study was undertaken as part of the on going Reproductive and Child Health Survey. A total of 5,690 participants age 18–44 were recruited for this study. Data were obtained through home interviews, and focused on socio-demographics, knowledge, attitudes and behaviors regarding sexuality, HIV/AIDS and other STDs.ResultsThe study revealed that only 22% of adults had even heard of AIDS, and 18 % knew how it is transmitted. In addition, only 5% knew that STDs and AIDS were related to each other. AIDS awareness among women was lower compared to men (14% vs.30 %). Regarding sexual practices, 35% of the respondents reported having had extramarital sexual encounters, with more males than females reporting extramarital affairs.ConclusionLack of awareness, permissiveness of tribal societies for premarital or extra-marital sexual relationships, and sexual mixing patterns predispose these communities to HIV/AIDS and STD infections. There is a dire need for targeted interventions in order to curtail the increasing threat of HIV and other STDs among these vulnerable populations.

Characteristics of HLA Class I and Class II Polymorphisms in Rwandan Women

Objective: To define HLA class I and class II polymorphisms in Rwandans. Methods: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. Results: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were ≥0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. Discussion: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Adherence to antiretroviral therapy in India: a systematic review and meta-analysis.

Objective: To assess the adherence to antiretroviral therapy (ART) in the human immunodeficiency virus (HIV)-infected population in India. Design: Systematic review and meta-analysis. Materials and Methods: The Medline and Cochrane library database were searched. Any prospective or retrospective study enrolling a minimum of 10 subjects with a primary objective of assessing ART adherence in the HIV population in India was included. Data were extracted on adherence definition, adherence estimates, study design, study population characteristics, recall period and assessment method. For metaanalysis, the pooled proportion was calculated as a back-transform of the weighted mean of the transformed proportions (calculated according to the Freeman-Tukey variant of the arcsine square root) using the random effects model. Results: There were seven cross-sectional studies and one retrospective study enrolling 1666 participants. Publication bias was significant (P = 0.003). Pooled results showed an ART adherence rate of 70% (95% confidence interval: 59–81%, I2 = 96.3%). Sensitivity analyses based on study design, adherence assessment method and study region did not influence adherence estimates. Fifty percent (4/8) of the studies reported cost of medication as the most common obstacle for ART adherence. Twenty-five percent (2/8) reported lack of access to medication as the reason for non-adherence and 12% (1/8) cited adverse events as the most prevalent reason for non-adherence. The overall methodological quality of the included studies was poor. Conclusion: Pooled results show that overall ART adherence in India is below the required levels to have an optimal treatment effect. The quality of studies is poor and cannot be used to guide policies to improve ART adherence.

Clinico-epidemiological profile of HIV/TB coinfected patients in Vadodara, Gujarat.

INTRODUCTION The HIV epidemic has posed major, almost insurmountable, challenges to tuberculosis control efforts across the world. This study analyzes the prevalence and disease profile of HIV/AIDS coinfection in Vadodara, Gujarat, India. MATERIALS AND METHODS This study was conducted in the HIV Referral Clinic at Vadodara, India. Using convenience sampling method, 246 HIV-positive patients coinfected with tuberculosis were enrolled. A detailed history of every case was taken followed by a thorough physical examination. Baseline and follow up laboratory and radiological investigations were carried out as appropriately warranted. RESULTS Out of 500 HIV positive patients who presented to the clinic during the study period, 246 (49.2%) were coinfected with tuberculosis. Out of 246 coinfected cases, 35(14.2%) presented with demonstrable and documented tuberculosis whereas in 211(85.8%) cases, tuberculosis was extemporaneously detected by actively screening the patients. Sixty nine percent of patients were males, while 10.5% of cases were below fifteen years of age. The majority (68%) of patients had manifestations of extrapulmonary tuberculosis; but pulmonary tuberculosis, which is a more common presentation in HIV-negative cases, was present in only fifty five percent of this segment of the population. Abdominal tuberculosis was the most common site (74%) amongst extrapulmonary tuberculosis involvement, followed by clinically palpable lymph nodes (22%) and pleural effusion (17%). CONCLUSION The prevalence of tuberculosis in HIV-positive patients in this study (49%) was substantially higher than that reported in previous studies. However, this could be attributed to a selection and/or a diagnosis bias. This study used abdominal ultrasound for the diagnosis of tuberculosis which might have obviously increased the prevalence. Moreover, these cases were not confirmed by biopsy or other definitive TB diagnostic methods.

Cost of treatment: The single biggest obstacle to HIV/AIDS treatment adherence in lower-middle class patients in Mumbai, India

BACKGROUND This study analyzes the social, economic and behavioral factors most frequently associated with adherence to Highly Active Antiretroviral Treatment (HAART) in urban India. MATERIALS AND METHODS Data was collected in a metropolitan teaching hospital in Mumbai using a cross-sectional survey design. Face-to-face interviews were conducted with 152 patients. The semistructured survey included both open and closed ended questions on socio-demographic, economic and behavioral factors. Factors affecting treatment adherence were analyzed. RESULTS The median age of patients was 40.5 years, 73% were males and all were heterosexual. Patients had been given ART from six months to five years (median is equal to 3.5). Ninety per cent lived at home and commuted to the clinic by bus or train. Behaviorally, 37% were sexually active, but only 55% used condoms. In assessing adherence, income, education, knowledge of their drugs, transportation, side effects, cost of treatment, distance from clinic and personal clinic satisfaction were analyzed. We found that 75% of patients reported cost of HAART to be the single greatest obstacle to adherence (p less than 0.01). Additionally, those claiming knowledge of their drugs were 2.3 times more likely to be adherent (p less than 0.03), while those who abused drugs or alcohol were 53% less likely to be adherent (p less than 0.03). There was no correlation with other factors. CONCLUSIONS Our study population was representative of the lower middle class of India. It found that an educated, employed group considered the cost of treatment to be a significant obstacle for successful therapy. Additionally, it showed a significant increase in adherence when patients had knowledge of their HAART medications. Therefore, reducing the cost of medication as well as teaching about antiretroviral medications are both likely to improve adherence.

Weekly chloroquine prophylaxis and the effect on maternal haemoglobin status at delivery.

Our aim was to determine the effectiveness of chloroquine prophylaxis in reducing the frequency of malaria‐induced anaemia at delivery. We estimated the haemoglobin levels of 207 parturients; 82 (39.6%) had been on chloroquine prophylaxis [treatment group (TG)] while 125 (60.4%) did not take any malaria preventive medication antenatally [control group (CG)]. The proportion of women with malaria parasitaemia was significantly higher in CG than TG [risk ratio (RR=1.57, CI=1.05–2.34)]. The dose–response relationship between the severity of parasitaemia and the risk of being anaemic (P < 0.001) confirms a strong correlation between gestational malaria and maternal anaemia. There was a 35% reduction in risk for anaemia in the TG compared with the CG (RR=0.65, 0.40–1.06). The difference in risk was more pronounced after adjusting for disparity in place of residence, educational status and obstetric history (adjusted RR=0.54, CI=0.21–0.98). Primiparous mothers appeared to have benefited more from the antianaemic effects of malaria chemoprevention than mothers of higher parity (protective effectiveness 43% compared with 33%, respectively). In conclusion, despite reports of widespread Plasmodium falciparum resistance to chloroquine on the African continent, malaria chemosuppression with the drug was found beneficial in reducing the risk of anaemia at delivery among Cameroonian women.

The complexity of HLA class II (DRB1, DQB1, DM) associations with disseminated Mycobacterium avium complex infection among HIV-1-seropositive whites

Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1) genes have been extended to include the accessory genes DMA and DMB as determinants of disseminated Mycobacterium avium complex (DMAC) infection among HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases were matched with 176 controls in a nested case-control study. PCR-based HLA genotyping techniques were used to resolve variants of DRB1 and DQB1 to their four-digit or five-digit alleles, and single-strand conformation polymorphism was used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele occurred less frequently among DMAC cases than among controls (OR = 0.46, p =.02). Combinations of DRB1 alleles with or without specific DMA and DMB variants showed significant differences in distributions between the cases and controls, but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701) showed stronger positive associations with DMAC in the absence than in the presence of DMA*0102. Apparent joint effects of DRB1 and DM allelic combinations on occurrence and timing of DMAC suggest that class II disease relationships may be better predicted by biologically plausible interactive combinations than by polymorphisms in individual genes.

Profile of HIV seroconcordant/discordant couples a clinic based study at Vadodara, India.

BACKGROUND Heterosexual transmission of HIV among married couples is the commonest mode of transmission seen in India. Intramarital transmission is associated with several challenges which need to be further researched. AIM To study level of seroconcordance and serodiscordance among HIV positive couples and factors affecting intramarital sexual transmission in terms of safe sexual practice, and the presence of Sexually transmitted infections (STI)/circumcision. MATERIALS AND METHODS Ninety-one monogamous married cohabiting HIV-positive cases (index cases) attending Department of Skin and Venereology, Medical College Baroda, from January 2009 to August 2009 were studied. Their spouses were tested for HIV. A structured proforma was used to study various factors like condom use, circumcision, and the presence of sexually transmitted infections. RESULTS Ninety-one monogamous married cohabiting HIV-positive cases were included in the study and considered as index cases. There were 51 males and 40 females. On testing their spouses for HIV, both the spouses were positive in 55 couples giving rise to 60% seroconcordance rate. Out of 55 seroconcordant couples, male spouses used condom in 16 cases (29%). Out of 36 serodiscordant couples 17 male spouses (47%) used condom. Evidence of STD was observed in one of the spouses in 6 out of 55 seroconcordant couples and 6 out of 36 serodiscordant couples. Thus, out of 91 couples one of the partners was having STI in 12 couples. Overall rate of circumcision was 12.2%. CONCLUSION The prevention of transmission of HIV to the HIV negative partner is of paramount importance. Serodiscordant couples, specially the HIV negative female partner is at higher risk. Less acceptability of condoms among married couples may be one of the factors responsible in transmission. Further studies are needed to explore other risk factors associated with HIV transmission in discordant couples.

Clinical outcome of novel H1N1 (Swine Flu)-infected patients during 2009 pandemic at tertiary referral hospital in western India

Background: The first case of 2009 pandemic influenza A (H1N1) virus in Gujarat, India, was reported in August 2009. Oseltamivir was used for treatment of pandemic influenza in India. We discuss the clinical characteristics and outcome of the hospitalized patients with H1N1 infection during 2009 pandemic influenza season. Materials and Methods: Hospitalized patient with laboratory-confirmed H1N1 flu during August 2009 to February 2010 were included in this retrospective study. Data were collected from hospital ICU charts. Patients discharged from hospital were considered cured from swine flu. Data analysis was performed using CDC software EPI Info v3.5.3. Both univariate and multivariate analyses were conducted. Results: A total of 63 patients were included in the study, of them 41 (65%) males and 22 (35%) females. Median age was 34 (3-69) years and median duration of symptoms before hospitalization was 5 (2-20) days. Common presenting symptoms include fever 58 (92.06%), cough 58 (92.06%), breathlessness 38 (60.31%), common cold 14 (22.22%), vomiting 12 (19.04%), weakness 9 (14.28%), throat pain 7 (11.11%), body ache 5 (7.93%), and chest pain 4 (6.34%). Co-morbidities were seen in 13 (20.63%) patients. Steroids were used in 39 (61.90%) patients, and ventilatory support was required in 17 (26.98%) patients. On presentation chest x-ray was normal in 20 (31.74%) patients, while pulmonary opacities were seen in 43 (68.26%) patients. Forty-seven (74.60%) patients were cured and discharged from hospital, 14 (22.22%) patients died, and 2 (3.17%) patients were shifted to other hospital. Ventilatory requirement, pneumonia, and co-morbidities were the independent predictors of mortality, while age, sex, and steroid use were not associated with increased mortality. Conclusion: 2009 pandemic influenza A had the same clinical features as seasonal influenza except vomiting. Mortality rate was high in 2009 H1N1-infected patients with pneumonia, co-morbid conditions, and patients who required ventilatory support.