Tokugha Yepthomi

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.

High Frequency of Clinically Significant Mutations after First-Line Generic Highly Active Antiretroviral Therapy Failure: Implications for Second-Line Options in Resource-Limited Settings

Continuation of failed highly active antiretroviral therapy regimens can lead to the accumulation of mutations that may limit options for second-line treatment. We studied the pattern of drug resistance mutations among 138 Indian patients who experienced failure of nonnucleotide reverse-transcriptase-containing first-line highly active antiretroviral therapy. This study demonstrates a high frequency of drug resistance mutations in human immunodeficiency virus-infected Indians who experience immunologic treatment failure and suggests the need for viral load monitoring.

Neurocognitive consequences of HIV in southern India: A preliminary study of clade C virus

The neurocognitive impact of the clade C viral strain of human immunodeficiency virus (HIV) has not been determined. The purpose of this study was to examine neurocognitive function in southern India among individuals with the clade C virus with advanced HIV. A battery of cognitive tasks sensitive to the effects of HIV on brain function was translated and administered in Tamil and Telegu, two widely spoken languages in southern India. A sample of 30 treatment-naïve HIV-positive individuals with a median CD4 cell count of 97, and 30 age and education matched healthy controls obtained from the same region of India, were included in the study. Results revealed significant differences on most cognitive tests, with lower performances obtained by the HIV-positive individuals. These results suggest that cognitive difficulties are present among individuals with the clade C virus in India, with as many as 56% of the patients with advanced HIV meeting the criterion for impairment in two cognitive domains. Additional study is needed to determine if clade C HIV infection is more or less prone to cause neurocognitive deficit than the clade B virus. Furthermore, the impact of antiretroviral therapy on neurocognitive dysfunction in clade C virual infection needs to be determined.

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.

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

OBJECTIVE To describe gender-based differences in disease progression, treatment, and outcome among patients receiving highly active antiretroviral therapy (HAART) in South India. METHODS Therapy-naïve patients initiating HAART between February 1996 and June 2006 at a tertiary HIV referral center in Chennai, South India, were analyzed using the YRG CARE HIV Observational Database. Patients with 1 year of follow-up after initiating HAART were examined to investigate immunological and clinical outcomes, including the development of adverse events to therapy and opportunistic infections. RESULTS All previously therapy-naïve patients who initiated HAART with at least 1 year of follow-up (n = 1972) were analyzed. At enrollment into care, women had higher CD4 counts, lower hemoglobin, and higher body mass index (BMI) than their male counterparts (p < 0.05). At the time of initiating therapy, women had higher CD4 counts and lower hemoglobin (p < 0.05); women continued to have higher CD4 counts at 12 months (p < 0.05). After 1 year following HAART initiation, significantly more men developed tuberculosis and Pneumocystis jiroveci pneumonia (p < 0.05), more women experienced lactic acidosis and nausea, and more men developed immune reconstitution syndrome (p < 0.05). CONCLUSIONS Significant physiological, immunological, and clinical differences exist between men and women initiating HAART in a resource-limited setting in South India. Future studies should examine whether clinical management strategies should be different for men and women in resource-limited settings.

Factors associated with anaemia in HIV-infected individuals in southern India.

Anaemia accelerates disease progression and increases mortality among HIV-infected individuals. Few studies have characterized this problem in developing countries. Haemoglobin values of adults presenting to an HIV tertiary care center in India between 1996 and 2007 were collected (n = 6996). Multivariate logistic regression analysis was performed to examine associations among anaemia, HIV progression and co-morbidities. Overall, anaemia prevalence was 41%. Twenty percent of patients with CD4 counts >500 cells/μL were anaemic, compared with 64% of those with CD4 counts P < 0.001). In multivariate analysis, CD4 count <100cells/μL (odds ratio [OR]:5.0, confidence interval [CI]:4.0–6.3), underweight body mass index (OR:4.8, CI:3.6–6.5), female gender (OR:3.1, CI:2.8–3.6) and tuberculosis (TB) (OR:1.6, CI:1.4–1.8) were significantly associated with anaemia. In this setting, management of anaemia should focus on antiretroviral therapy, nutritional supplementation and TB control. The high anaemia prevalence among patients meeting criteria for antiretroviral therapy highlights the need for increased access to non-zidovudine nucleoside reverse transcriptase inhibitors in developing countries.

Clinical outcomes among HIV/tuberculosis-coinfected patients developing immune reconstitution inflammatory syndrome after HAART initiation in South India.

Introduction: We determine the frequency and immunological outcome of developing immune reconstitution inflammatory syndrome (IRIS) among HIV/tuberculosis (TB)–coinfected Indians receiving highly active antiretroviral therapy (HAART). Methods: Patients coinfected with TB and HIV who initiated HAART were classified based on treatment outcomes (IRIS and non-IRIS) utilizing an observational HIV/AIDS cohort. Results: A total of 1731 HIV/TB-coinfected patients initiated HAART, and 95 of these patients (5.5%) developed TB-IRIS, with an incidence rate of 0.26 per 100 person-years. Patients who developed IRIS had significantly higher CD4 counts than non-IRIS patients at the time of initiating HAART, as well as after 6 months, 18 months, and 24 months following HAART initiation (P < .05). Conclusions: HIV/TB-coinfected patients who developed IRIS following HAART initiation had equivalent clinical outcomes compared with their HIV/TB-coinfected counterparts who did not develop IRIS, suggesting minimal long-term risks associated with IRIS.

Safety tolerability and efficacy of second-line generic protease inhibitor containing HAART after first-line failure among South Indian HIV-infected patients.

Introduction: We describe the safety, tolerability, and efficacy of protease inhibitor (PI) containing highly active antiretroviral therapy (HAART) among patients switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based HAART from a clinical setting in South India. Methods: We assessed a prospective cohort of 91 HIV-infected patients with at least 12 months of clinical follow-up on second-line ritonavir-boosted PI-based therapy between August 2003 and December 2008. Results: More than three fourths of patients met the World Health Organization (WHO) criteria for immunological failure at the time of switch. The median time to switch was 758 days. Patients demonstrated consistent increases in their CD4 counts during the first 12 months, by which time the median CD4 count was 322 cells/mm3. The most common adverse events within the first year after switch were nausea (14.8%), lipodystrophy (10.4%), and peripheral neuropathy (7.0%). Patients switching to atazanavir (ATV)-based regimens compared to those switching to indinavir (IDV)-based regimens had similar immunological and clinical outcomes. Conclusions: Given the therapeutic success of using second-line PI-containing HAART after experiencing treatment failure, further efforts must be taken to expand access to second-line HAART so that more patients can benefit from these drugs.

Safe substitution to zidovudine among HIV-infected patients initiated on stavudine-containing highly active antiretroviral therapy from a resource-limited setting

OBJECTIVE To describe the safe substitution with zidovudine (AZT) among South Indian HIV-infected patients who were initiated with stavudine (d4T)-containing highly active antiretroviral therapy (HAART) due to anemia. METHODS Therapy-naïve patients initiating HAART between January 2006 and December 2007 and who had had d4T substituted for AZT at a tertiary HIV referral center in India were analyzed. RESULTS Six hundred and nineteen patients initiated d4T-containing HAART (median CD4 110 cells/microl; median hemoglobin 10.4 g/dl) during the study period. Subsequently half of these patients substituted d4T for AZT (median CD4 350 cells/microl; median hemoglobin 12.8 g/dl). After substituting with AZT, three patients (2.7%) who substituted after less than 6 months and one patient (0.6%) who substituted at between 6 and 12 months developed anemia. Patients who substituted after less than 6 months had significantly higher median CD4 cell counts at 1-month and 6-months of follow-up than patients who substituted at between 6 and 12 months (p<0.05). Few patients (1.6%) experienced treatment failure; about a tenth of patients developed d4T-related toxicities. CONCLUSION Few patients developed anemia (1.4%) within 6 months of substitution with AZT. In settings where tenofovir is either expensive or not available and where patients are anemic, initiating d4T followed by prompt substitution with AZT can be a safe and tolerable treatment option.

Impact of generic antiretroviral therapy (ART) and free ART programs on time to initiation of ART at a tertiary HIV care center in Chennai, India

Antiretroviral therapy (ART) access in the developing world has improved, but whether increased access has translated to more rapid treatment initiation among those who need it is unknown. We characterize time to ART initiation across three eras of ART availability in Chennai, India (1996–1999: pregeneric; 2000–2003: generic; 2004–2007: free rollout). Between 1996 and 2007, 11,171 patients registered for care at the YR Gaitonde Centre for AIDS Research and Education (YRGCARE), a tertiary HIV referral center in southern India. Of these, 5726 patients became eligible for ART during this period as per Indian guidelines for initiation of ART. Generalized gamma survival models were used to estimate relative times (RT) to ART initiation by calendar periods of eligibility. Time to initiation of ART among patients in Chennai, India was also compared to an HIV clinical cohort in Baltimore, USA. Median age of the YRGCARE patients was 34 years; 77% were male. The median CD4 at presentation was 140 cells/µl. After adjustment for demographics, CD4 and WHO stage, persons in the pregeneric era took 3.25 times longer (95% confidence interval [CI]: 2.53–4.17) to initiate ART versus the generic era and persons in the free rollout era initiated ART more rapidly than the generic era (RT: 0.73; 95% CI: 0.63–0.83). Adjusting for differences across centers, patients at YRGCARE took longer than patients in the Johns Hopkins Clinical Cohort (JHCC) to initiate ART in the pregeneric era (RT: 4.90; 95% CI: 3.37–7.13) but in the free rollout era, YRGCARE patients took only about a quarter of the time (RT: 0.31; 95% CI: 0.22–0.44). These data demonstrate the benefits of generic ART and government rollouts on time to initiation of ART in one developing country setting and suggests that access to ART may be comparable to developed country settings.