A longitudinal quality-of-life study of HIV-infected persons in South India: the case for comprehensive clinical care and support services.

This study longitudinally assesses the quality of life (QOL) of HIV-infected individuals in a resource-limited setting prior to the extensive generic roll-out of highly active antiretroviral therapy. Data was collected on 136 individuals receiving clinical care at Y.R. Gaitonde Centre for AIDS Research and Education YRG CARE, a large community-based HIV tertiary care referral center in Chennai, South India. The QOL questionnaire was administered to participants at baseline, 6-months follow-up, and 12-month follow-up, and analysis of variance was used to assess for significant differences in mean QOL scores for each of these visits. Study findings showed that QOL scores significantly improved in all five domains of the questionnaire between participants' baseline visit, second interview, and third interviews (p < 0.01). We conclude that a multidisciplinary approach to managing HIV infection can enhance patients' QOL, independent of antiretroviral therapy.

Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients.

To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.

Use of an HIV-1 reverse-transcriptase enzyme-activity assay to measure HIV-1 viral load as a potential alternative to nucleic acid-based assay for monitoring antiretroviral therapy in resource-limited settings.

An inexpensive and technically less-demanding methodology to quantify HIV-1 viral load would be of great value for resource-limited settings, where the nucleic-acid amplification technique (NAAT) is impractical and/or resource-prohibitive. In this study, an HIV-1 reverse-transcriptase enzyme-activity assay (ExaVir Load assay, version 1) was compared with the gold standard RT-PCR assay, Roche HIV-1 Amplicor Monitor, version 1.5. A total of 121 plasma specimens were used for the evaluation. ExaVir Load had a sensitivity of 97 % and a specificity of 71 % in identifying specimens with <400 copies ml(-1) in the Roche RT-PCR assay as being less than the detection limit of the assay (5500 copies ml(-1)). The mean difference (95 % limits of agreement) between Roche RT-PCR and ExaVir Load was -0.23 (-1.59 to 1.13) log(10)(copies ml(-1)) by Bland-Altman analysis. Significant negative correlations were seen between CD4(+) T-cell counts and the ExaVir Load assay (r=-0.32, P<0.05), and between CD4(+) T-cell counts and the Roche RT-PCR (r=-0.38, P<0.01). The present study with HIV-1 showed a strong correlation between the ExaVir Load assay and the RT-PCR assay. Hence, the ExaVir Load assay could be considered for use in resource-limited settings as an alternative viral-load assay to the standard NAAT-based assay after further evaluation with prospective specimens.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy.

BACKGROUND: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. OBJECTIVE: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. METHODS: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. RESULTS: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. CONCLUSIONS: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.

Weight and body shape changes in a treatment-naive population after 6 months of nevirapine-based generic highly active antiretroviral therapy in South India.

BACKGROUND: The nutritional and body shape response after the initiation of highly active antiretroviral therapy (HAART) in resource-limited environments has not been documented. In this environment, nutritional compromise is a common complication of human immunodeficiency virus (HIV) infection. METHODS: We conducted a prospective study of 190 HIV-infected patients who initiated a nevirapine-based HAART regimen. CD4+ T cell count, body weight, body mass index, anthropometry, and bioelectrical impedance data were collected prior to initiation of therapy and after 6 months of therapy. RESULTS: The mean age of participants was 35 years, 85% of participants were male, and 59% received stavudine as 1 of the nucleosides in their initial HAART regimen. The members of the cohort were malnourished before the initiation of therapy and had a mean body mass index of 20.1 (calculated as weight in kilograms divided by the square of height in meters). Overall, body weight increased a mean of 2.8 kg (range, -12.5 to 22.5 kg), and CD4+ T cell counts increased by a mean of 140 cells/mm3. Patients were stratified into those who lost weight (loss of >1 kg, 22%; n=41), those whose weight remained stable (19%; n=37), and those who gained weight (gain of >1 kg, 59%; n=112). Patients in all groups retained body shape symmetry and experienced no change in waist-to-hip ratio or regional body shape by anthropometry. CONCLUSIONS: The group that lost weight and the group whose weight remained stable experienced significant CD4+ T cell count increases at 6 months. Although the majority of HIV-infected patients who received nevirapine-based HAART gained weight, there were participants who lost weight despite initiating their first HAART therapy.

A reliable and inexpensive EasyCD4 assay for monitoring HIV-infected individuals in resource-limited settings.

Serial measurements of absolute CD4+ T-lymphocyte counts are required to initiate and gauge response to therapy and monitor disease progression. Hence, there is an urgent need to evaluate the accuracy and validity of low-cost CD4+ T-cell count assays. Tripotassium EDTA blood specimens from HIV-infected individuals were studied using a novel flow cytometric assay (EasyCD4 assay; Guava Technologies, Hayward, CA) in comparison with standard flow cytometry (FACSCount; Becton Dickinson Immunocytometry Systems, San Jose, CA). The sensitivity, specificity value by EasyCD4 assay in enumerating absolute CD4+ T-cell counts of less than 200 cells/microL were 95% and 100%, respectively. Bland-Altman analysis showed close agreement, with the EasyCD4 assay yielding CD4+ T-cell counts a mean difference of -26 cells/microL (95% confidence interval, -96 to 44 cells/microL) higher than by flow cytometry. Our data suggest that EasyCD4 assay could be a useful alternative assay to conventional flow cytometry, may be appropriate for use in resource-limited settings.

Why are people getting tested? Self-reported reasons for seeking voluntary counseling and testing at a clinic in Chennai, India.

VCT has been shown to be an important HIV risk reduction strategy; however, little is known about who attends VCT or why people seek VCT. A retrospective analysis was performed on charts of 6330 clients who attended VCT between 1994 and 2002 at Y.R. Gaitonde Centre for AIDS Research and Education, a non-governmental organization in Chennai, Tamil Nadu, India. Most clients reported more than one reason for attending VCT, and the most commonly reported reasons were risk behavior, having symptoms, having a current HIV-positive partner, and reconfirming a previous positive HIV test. Reasons varied by gender and over time, and the likelihood of testing positive for HIV varied by reason reported. Understanding why people seek VCT informs an understanding of knowledge and attitudes about HIV and HIV testing, which has implications for the development of education, outreach and other HIV prevention services.

Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India.

OBJECTIVE: To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India. METHODS: Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database. RESULTS: All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%). CONCLUSION: The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.

The changing natural history of HIV disease: before and after the introduction of generic antiretroviral therapy in southern India.

The number of individuals seeking treatment for infection with human immunodeficiency virus increased as the cost of highly active antiretroviral therapy (HAART) decreased 20-fold after the introduction of generic HAART in India in the year 2000. The incidence of tuberculosis and opportunistic infections decreased to <2 cases per 100 person-years. Death rates decreased from 25 to 5 deaths per 100 person-years between 1997 and 2003.

An inexpensive, simple, and manual method of CD4 T-cell quantitation in HIV-infected individuals for use in developing countries.

CD4+ T lymphocytes are currently the most common surrogate marker indicating immune status and disease progression with HIV infection. The cost of monitoring disease progression and response to therapy is still prohibitively expensive. Flow cytometry is the gold standard for the estimation of CD4+, but the high initial investment for this technology and expensive reagents makes it unaffordable for developing countries like India. We evaluated the Coulter cytosphere assay for quantifying CD4+ T lymphocytes in comparison with the standard method, flow cytometry, in 122 HIV-infected individuals. The correlation coefficient of the cytosphere assay compared with that of flow cytometry for CD4+ T lymphocytes was 0.97 (P< 0.0001), with a confidence interval of 0.95 to 0.98. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytosphere assay in enumerating absolute CD4+ T-lymphocyte counts of less than 200/microL were 94.9%, 96.4%, 92.5%, and 97.6%, respectively. This is a simple inexpensive method and has a strong correlation with flow cytometry. Hence, the cytosphere assay can be an alternate to flow cytometry for the estimation of CD4+ T-lymphocyte counts, especially in resource-poor settings of developing countries, for monitoring HIV progression and response to therapy.