Symposium on bioethics: empowerment of research participants/patients.

YRG CARE conducted The YRG CARE Bioethics Symposium (TYBS) in collaboration with the National Institute of Epidemiology (NIE), the Indian Council of Medical Research (ICMR), Chennai, through the National Institutes of Health Project “Centrally Coordinated Bioethics Education for India” and the National Institute for Research in Tuberculosis (NIRT), ICMR, Chennai on January 6, 2013.

Immunologic response among HIV-infected patients enrolled in a graduated cost-recovery programme of antiretroviral therapy delivery in Chennai, India.

Background & objectives: Sustainability of free antiretroviral therapy (ART) roll out programmes in resource-limited settings is challenging given the need for lifelong therapy and lack of effective vaccine. This study was undertaken to compare treatment outcomes among HIV-infected patients enrolled in a graduated cost-recovery programme of ART delivery in Chennai, India. Methods: Financial status of patients accessing care at a tertiary care centre, YRGCARE, Chennai, was assessed using an economic survey; patients were distributed into tiers 1- 4 requiring them to pay 0, 50, 75 or 100 per cent of their medication costs, respectively. A total of 1754 participants (ART naïve = 244) were enrolled from February 2005-January 2008 with the following distribution: tier 1=371; tier 2=338; tier 3=693; tier 4=352. Linear regression models with generalized estimating equations were used to examine immunological response among patients across the four tiers. Results: Median age was 34; 73 per cent were male, and the majority were on nevirapine-based regimens. Median follow up was 11.1 months. The mean increase in CD4 cell count within the 1st three months of HAART was 50.3 cells/μl per month in tier 1. Compared to those in tier 1, persons in tiers 2, 3 and 4 had comparable increases (49.7, 57.0, and 50.9 cells/μl per month, respectively). Increases in subsequent periods (3-18 and >18 months) were also comparable across tiers. No differential CD4 gains across tiers were observed when the analysis was restricted to patients initiating ART under the GCR programme. Interpretation & conclusions: This ART delivery model was associated with significant CD4 gains with no observable difference by how much patients paid. Importantly, gains were comparable to those in other free rollout programmes. Additional cost-effectiveness analyses and mathematical modelling would be needed to determine whether such a delivery programme is a sustainable alternative to free ART programmes.

HIV serodiscordant relationships in India: Translating science to practice.

Over the past 30 years, several interventions have been identified to prevent HIV transmission from HIV-infected persons to uninfected persons in discordant relationships. Yet, transmissions continue to occur. Interventions such as voluntary counselling and testing, condom promotion and risk reduction counselling are very effective in preventing transmission among serodiscordant couples but are underutilized in India despite their widespread availability. New interventions such as pre-risk exposure prophylaxis and universal antiretroviral therapy (irrespective of CD4 count) have been newly identified but face several challenges that impede their widespread implementation in India. Discordant couples in India also face certain unique socio-cultural issues such as marital and fertility pressure. We briefly review the various interventions (existing and novel) available for persons in discordant relationships in India and socio-cultural issues faced by these individuals and make recommendations to maximize their implementation.

Low-cost assays for monitoring HIV infected individuals in resource-limited settings.

Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.

HIV-1 Drug Resistance Among Newly HIV-1 Infected Individuals Attending Tertiary Referral Center in Chennai, India.

Context: In the era of free HAART, accessibility and availability of ARV has been dramatically increased in India. However, rates of treatment literacy and adherence appear to be sub-optimal. Therefore, it is essential to monitor the extent of primary drug resistance in such settings. Materials and Methods: Between July and October 2006, 18 anti-retroviral-naοve individuals were identified as recent infected by the BED-Capture enzyme immunoassay in a VCTC clinic in Chennai. Specimens from these individuals were subjected to genotypic drug resistance testing. Phylogenetic trees were generated using MEGA for Windows version 4.0 using neighbor-joining method. The significant differences in polymorphic mutation frequencies between the study specimens and established subtype C-specific polymorphisms were examined using the Chi-square test. Results: Amino acid substitution (K103N and V106MV) at drug resistance positions occurred in two (11%) isolates, conferring high-level resistance to the non-nucleoside reverse-transcriptase inhibitors nevirapine (NVP), efavirenz (EFV), delavirdine (DLV) and notably extensive genetic variations were observed. K122E (94.4%) and K49R/KR (11.1%) polymorphisms identified in this study have not been previously described in established subtype-C specific polymorphisms. The rate of polymorphisms showed marked difference at the locations V60, D121, V35, and D123 (P < 0.0001). All the sequences showed maximum homology with Indian HIV-1 subtype C reference strain C.IN.95IN21068. Conclusions: The finding of resistance to NNRTIs is of public health importance. There is an urgent need to establish surveillance for primary drug resistance in large scale. Further studies are required to determine the phenotype impact of newer polymorphic mutations in relation to drug resistance and viral fitness.

Epidemiology of hepatitis C virus infection & liver disease among injection drug users (IDUs) in Chennai, India.

Background & Objectives: We characterized HCV antibody prevalence, viral persistence, genotype and liver disease prevalence among IDUs in Chennai, India as the study of the association of HIV with each of these states is important and there are no data available. Methods: Between 2005-2006, 1158 IDUs were recruited and followed semi-annually. All were tested for HCV antibodies at baseline; a random sample of 400 antibody positives (200 HIV-positive and 200 HIV-negative) were tested for HCV RNA; 13 of these were sequenced. Assessment of asparate amino transferase (AST)-to-platelet ratio index (APRI) was done on 557 IDUs. Prevalence ratios of each outcome were examined. Results: Median age was 35 yr; 99 per cent were male. HCV antibody prevalence was 55 per cent and was associated with older age, being unmarried, longer injection history, tattoo and injecting at a dealer’s place. Of the 400 HCV antibody positive IDUs, 281 (70.3%) had persistent infection which was less common among hepatitis B-infected persons but not associated with HIV. Of the 13 samples sequenced, 11 (85%) were HCV genotype 3a. Fibrosis prevalence according to APRI was: HIV/HCV-uninfected, 4 per cent; HIV mono-infected, 3 per cent; HCV mono-infected, 11 per cent; HIV/HCV co-infected, 12 per cent (P<0.001). In addition to being associated with HCV and HIV/HCV, fibrosis prevalence was higher among those drinking alcohol frequently; daily marijuana use was protective. Interpretation & Conclusions: Our findings show that IDUs in Chennai have high HCV prevalence and associated disease burden. The burden will increase as access to antiretroviral therapy improves particularly given the high prevalence of HIV, HCV and alcohol use.

A Descriptive Profile of Abused Female Sex Workers in India.

This descriptive study presents the profiles of abused female sex workers (FSWs) in Chennai, India. Of 100 abused FSWs surveyed using a structured questionnaire, severe forms of violence by intimate partners were reported by most (98%) respondents. Of the total sample, 76% experienced violence by clients. Sexual coercion experiences of the FSWs included verbal threats (77%) and physical force (87%) by intimate partners and forced unwanted sexual acts (73%) by clients. While 39% of the women consumed alcohol before meeting a client, 26% reported that their drunkenness was a trigger for violence by clients. The findings suggest that there is an urgent need to integrate services, along with public-health interventions among FSWs to protect them from violence. Recognition of multiple identities of women in the contexts of intimate relationships versus sex work is vital in helping women to stay safe from adverse effects on health.

Establishment of T-lymphocyte subset reference intervals in a healthy adult population in Chennai, India.

Estimation of CD4+ T-lymphocytes continues to be an important aspect for monitoring HIV disease progression and response to antiretroviral therapy. Most of the diagnostic laboratories often rely on western text books for CD4+ T-lymphocyte reference values, which could, often be unreliable for usage in local settings. Therefore, we attempted to establish the reference values for T-lymphocyte subsets among healthy adults in a cross-sectional study carried out at the YRG Centre for AIDS Research and Education (YRG CARE) in Chennai, south India, in 213 (84 female and 129 male) healthy, HIV-1/2 seronegative adults as volunteers. Whole blood specimens were processed for CD4+, CD8+ T-lymphocyte estimation and haematological parameters. The established range of CD4+ T-lymphocyte counts for men and women were 383-1347 cells/microl (mean 865 and median 845 cells/microl) and 448-1593 cells/microl (mean 1021 and median 954 cells/microl), respectively. Women had significantly higher absolute CD4+ Tlymphocyte counts (P<0.001) and CD4+:CD8+ T-lymphocyte ratio as compared to men. The established normal range of CD4+ T-lymphocyte % was 21-59 (mean 40.2 and median 40.1). The influence of age was not observed in any of the parameters except CD4+/CD8+ T-lymphocyte ratio with the >45 yr age group. Further studies with greater sample size may be required to define the staging of HIV disease in relation to the normal CD4 T-lymphocyte count in the general population.

Comorbidities among HIV-infected injection drug users in Chennai, India.

BACKGROUND & OBJECTIVE: HIV-infected injection drugs users (IDUs) are known to have high rates of co-infections. A few reports exist on comorbidities among HIV-infected IDUs in India. We carried out a retrospective study to analyse data on comorbidities in India and treatment challenges faced when treating HIV-infected IDUs in India. METHODS: A retrospective chart review of 118 HIV-infected IDUs who accessed care at the YRG Centre for Substance Abuse-Related Research, Chennai, between August 2005 and February 2006 was done. Demographic, laboratory and clinical information was extracted from medical records. Descriptive demographic and clinical characteristics and distributions of comorbidities across CD4 cell count strata were analysed. RESULTS: All IDUs were male with a median age of 35.5 yr. The majority were married with average monthly income less than INR 3000 per month. The prevalence of hepatitis B and C infections were 11.9 and 94.1 per cent, respectively. Other common co-morbidities included oral candidiasis (43.2%), tuberculosis (33.9%), anaemia (22.9%), lower respiratory tract infections (16.1%), cellulitis (6.8%), herpes zoster (9.3%) and herpes simplex (9.3%). Among participants with CD4+ < 200 cells/microl, the prevalence of TB was 60 per cent. INTERPRETATION & CONCLUSION: IDUs in Chennai were commonly co-infected with HBV, HCV and tuberculosis, complicating use of antiretroviral and anti-tuberculous therapy. The current regimens available for the management of HIV and TB in India may need to be re-assessed for IDUs given the potential for increased rates of hepatotoxicity.

Greater severity and extent of periodontal breakdown in 136 south Indian human immunodeficiency virus seropositive patients than in normal controls: a comparative study using community periodontal index of treatment needs.

Apart from the more or less distinctive forms of periodontal disease associated with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome there remains considerable uncertainty as to whether or not conventional destructive periodontitis is exacerbated in HIV positive individuals. This is especially so in developing countries, from which few studies have been reported. The present study compared the severity and extent of periodontal break down in 136 HIV positive individuals from Chennai, South India, with 136 age-matched controls from the same low socio-economic and ethnic group. All surfaces of all teeth were scored for the community periodontal index of treatment needs (CPITN). Statistical analysis was performed using SPSS package. The results of the present study show that CPITN is a simple, useful technique to assess periodontal status in immunosuppressed patients and that periodontitis is associated with immunosuppression and oral candidiasis. The assessment of periodontal statuscould thus be a useful tool in minimally invasive screening of populations for HIV disease, especially in those parts of the world, like India and Africa, with high prevalence and rising incidence.

An approach to addressing ethical issues in a community-based risk assessment for HIV: a case from Chennai, India.

Community-based assessment of HIV prevalence and behavioural risk factors is the basis for deciding priorities of prevention and care programmes. Here, upholding the human rights of participants in assessment is of utmost importance. The objective of the paper was to describe the process of implementation of an epidemiological survey to assess HIV-related behavioural and biological factors in Chennai city in South India and to suggest an ethical framework for conducting similar assessment activities in developing-country settings. A survey was conducted with participation from residents (n=1,659) of low-income urban communities (slums) as part of a community-based HIV/STD-prevention trial. Administration of the survey was preceded by extensive community contact and household visits to inform community members about the trial and assessment activities. Formative research further strengthened rapport with community, highlighted community concerns, and identified HIV-related risk behaviours that informed questionnaire design. The process of obtaining informed consent began before assessment activities and provided an opportunity for individuals to discuss participation with their families and friends. Privacy during assessment, comprehensive follow-up care for those who tested positive for HIV/STDs, such as nutritional and prevention counselling, referral services for opportunistic infections, and antenatal-care options for pregnant women increased trust and credibility of the project. The sustained availability of trial staff to facilitate access to resources to address non-HIV/STD-related felt-needs further strengthened participation of the community members. These resources included liaison services with local government to obtain public services, such as water and electricity and resources, to address concerns, such as alcohol abuse and domestic violence. Based on this experience, an ethical framework is suggested for conducting HIV epidemiological risk assessment in developing countries. This framework discusses the role of community participation, transparent and comprehensive informed consent, timely dissemination of results, and access to follow-up care for those living with HIV/STDs.

Preparing for efficacy trials of vaginal microbicides in Indian women.

Vaginal microbicides are topical compounds that are expected to protect women against vaginal transmission of HIV and other sexually transmitted pathogens. A large number of compounds are being evaluated as possible microbicides. Considering the spread of the HIV epidemic among women in India, clinical trials on microbicides starting from the Phase I safety and acceptability studies to Phase III efficacy trials are important. Conducting efficacy trials is a major endeavour and this review discusses challenges and issues and the preparatory steps to make such efficacy trials possible in India.

Clinical profile of HIV in India.

The clinical course of human immunodeficiency virus (HIV) disease and pattern of opportunistic infections varies from patient to patient and from country to country. The clinical profile of HIV disease in India includes a wide range of conditions like tuberculosis, cryptococcal meningitis, popular pruritic eruptions, and cytomegalovirus retinitis, among others. Tuberculosis is the most common opportunistic infection in Indian patients with HIV. Occurrence of various AIDS-associated illnesses determines disease progression. Mean survival time of Indian patients after diagnosis of HIV is 92 months. In this review, we discuss the clinical profile of HIV disease through an organ system-based approach. With the availability of antiretroviral therapy at lower cost, the clinical profile of HIV disease in India is now changing to include drug-related toxicities and immune reconstitution syndrome.

Low-cost monitoring of HIV infected individuals on highly active antiretroviral therapy (HAART) in developing countries.

The standard methods to monitor HIV infection are flow cytometry-based for CD4+ T lymphocyte count and molecular assays to quantify plasma viral load of HIV. Few laboratories in resource-limited countries can run these tests as a majority of the HIV infected individuals are poor. A number of currently available low-cost assays which require less expensive equipment and reagents, may be well-suited to such countries. These include manual and ELISA based CD4 cell assays, and ultrasensitive reverse transcriptase quantitation (Cavidi) and p24 (ELAST) assays to monitor virus load. But better internal quality assurance and quality control (QA/QC) programmes are essential. This review discusses the low-cost assays and their role in clinical monitoring of HIV infected individuals in resource-limited countries like as India.

A Comparison of the Delivery of Antiretroviral Therapy System between Brazil and India

The similarities in size, trend of the epidemic, the generic drug industries and the high poverty levels between India and Brazil help to draw comparisons with regards to their ART delivery system. In Brazil, the Unified Health Systems, created in 1988 to address the health care needs of PLWHA, played a crucial role in the implementation of the policy of free universally available ART. Brazil used its resources to train physicians with the latest standards of care in the diagnosis, counseling and treatment of HIV/AIDS as well as to set up a 424 AIDS Drugs Dispensing Units (ADDU) . SILCOM and SISCEL are seen as Brazil’s most valuable tools in overcoming the challenges that face efficient delivery of ART. In phase I of the National AIDS Control Program, India selected fifteen institutions in six states to train physicians on counseling, diagnosis and treatment of HIV/ AIDS. Each hospital set up has an anti retroviral unit for adults and children with a family meeting room to discuss coping mechanisms related to their treatment. Each unit has a research officer, a counselor, a record keeper and a computer with a printer. The record keeper at each unit keeps track of the monthly progress report and performs quarterly cohort analysis. India and Brazil facing similarly challenging situations with HIV/AIDS have a lot to learn from each other to improve their deliver systems of ART for PLWHA.

Clinical manifestations of HIV infected children.

OBJECTIVE: Heterosexual contact is the predominant mode of transmission among adults in India with an increasing number of women of childbearing age becoming infected with HIV. Consequently, children in India increasingly getting infected, primarily from vertical transmission. A retrospective review of the profile of HIV infected children attending an HIV clinic in South India is reported. METHODS: All HIV-infected children under 15 years of age at the time of first presentation and managed at this center between June 1996 and June 2000 are included in this report. Socio-demographic characteristics and clinical manifestation were collected in a precoded proforme. A complete physical examination and baseline laboratory investigations were performed at entry into the clinic and at subsequent follow-up. RESULTS: Fifty-eight HIV-infected children were included: thirty-nine (67.2%) were male with mean age 4 years. Perinatal transmission was the predominant mode of HIV acquisition (67%). Common clinical manifestations in these children at presentation included oral candidiasis (43%), pulmonary tuberculosis (35%), recurrent respiratory infections (26%), bacterial skin infection (21%), papulo-pruritic dermatitis (19%), hepatosplenomegaly and lymphadenopathy (14%) each and chronic diarrhea (7%). CONCLUSION: An understanding of the epidemiology of pediatric HIV infection may reveal opportunities to reduce and perhaps eliminate perinatal transmission. Knowledge of clinical manifestations in this setting will help physicians meet the management challenges presented by HIV infected children.