Anitha J. Cecelia

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.

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/μL 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.

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.

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/μl (SD 291 cells/μl). 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

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

/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/μl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/μl. Lifetime medical costs ranged from US

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

530 (no ART) to US

Gender-Based Differences in Treatment and Outcome among HIV Patients in South India

5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US

Why are People Getting Tested? Self-Reported Reasons for Seeking Voluntary Counseling and Testing at a Clinic in Chennai, India

430/YLS to US

Weight and Body Shape Changes in a Treatment-Naive Population after 6 Months of Nevirapine-Based Generic Highly Active Antiretroviral Therapy in South India

550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/μl to <350 cells/μl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US

Rapid viral load suppression following generic highly active antiretroviral therapy in Southern Indian HIV-infected patients.

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.