Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB coinfected patients in India.

SETTING: Y R Gaitonde Centre for AIDS Research and Education, Chennai, India. OBJECTIVE: To compare anti-tuberculosis treatment outcomes in individuals with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin (RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg. DESIGN: A retrospective study was conducted of two HIV-TB co-infected cohorts between 2003 and 2014. Basic demographic and TB outcome data were obtained from an electronic database and patient records. The χ(2) and Fisher's exact test were used to compare daily and intermittent RBT treatment groups. RESULTS: Of 292 individuals on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar in sex, age, previous history of TB, site of TB and acid-fast bacilli smear status. More individuals in the daily vs. the intermittent RBT group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups. CONCLUSION: There were higher rates of clinical TB cure in individuals on a boosted protease inhibitor-based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal RBT dosing in this setting requires further investigation.

A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India.

BACKGROUND: The converging epidemics of HIV and tuberculosis (TB) pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. OBJECTIVE: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS) assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB) directly from sputum specimens, in the Indian setting. MATERIALS AND METHODS: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. RESULTS: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P<0.001). CONCLUSION: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way 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/microL were anaemic, compared with 64% of those with CD4 counts <100 cells/microL (P < 0.001). In multivariate analysis, CD4 count <100 cells/microL (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.

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.

A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India.

This randomised control trial, conducted in Chennai, India, compared structured interrupted therapy (SIT) and continuous therapy (CT) in relation to immunologic and virologic outcomes, adverse events (AEs) and cost of therapy. ART-naïve adult HIV1-infected participants with CD4 counts 50-350 cells/mm(3), and plasma viral load (PVL)>5000 copies/mL were enrolled and placed on Indian-manufactured generic ART: zidovudine(AZT)/stavudine(d4T)+lamivudine(3TC)+efavirenz(EFV). After at least six months of continuous therapy, subjects were randomised to SIT (one-week-on/one-week-off cycles) or CT. The primary end-point was the proportion of subjects maintaining CD4>200 cells/mm(3) at six and 12 months after randomisation. Secondary end-points were effective viral suppression (PVL<400 copies/mL), AEs and cost. All analyses used intention-to-treat methodology. Of 40 participants (69% male; mean age 36+/-7; median baseline CD4 and PVL: 162 cell/mm(3)and 259,000 copies/mL), 17 were randomised to SIT and 18 to CT. At randomisation, median CD4s for SIT and CT were 378 cells/mm(3) and 357 cells/mm(3), respectively. All participants had PVL<400 copies/mL at time of randomisation. Median CD4 six months after randomisation was 498 cells/mm(3) and 417 cells/mm(3) for SIT and CT respectively. All participants had CD4>200 cells/mm(3). One participant on CT and two on SIT had sustained PVL>400 copies/mL. There were no serious AEs or deaths. Structured interrupted therapy cost was half of CT. Structured interrupted therapy was effective at maintaining CD4 above 200 cells/mm(3). Adverse events were comparable in both groups, with 50% reduction in cost for SIT. Further research on such strategies may benefit resource-constrained settings.

Trends in HIV-related morbidity among patients admitted to a South Indian tertiary hospital between 1997 and 2003.

This paper describes trends in HIV-related morbidity among people living with HIV/AIDS (PLWHA) admitted to a tertiary hospital in Chennai, South India, between 1997 and 2003. Patients comprised HIV-infected men, women and children who had been admitted at least once to YR Gaitonde Centre for AIDS Research and Education (YRGCARE). A non-parametric trends analysis was conducted to observe trends in clinical and demographic parameters and diagnoses at admission over the seven-year period. Among clinical and demographic parameters, we identified a significantly increasing time trend in the use of antiretroviral therapy (p<0.001) and a significant decrease in the mean hemoglobin level (p=0.01). Among diagnoses at admission, we identified a decreasing time trend for admissions due to pulmonary tuberculosis (p<0.001) and increasing trends for admissions due to extra pulmonary tuberculosis (p<0.01), toxoplasmosis (p<0.01), Pneumocystis carinii pneumonia (p=0.02) and anemia (p<0.001). The results indicate a changing pattern among the clinical conditions requiring admission. With increasing proportions of patients initiating highly active antiretroviral therapy (HAART), it is probable that adverse events due to HAART will account for larger proportions of admissions in the years to come, as is being seen in the industrialized countries.

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.

Regression of attained milestones in an HIV infected infant.

We report a case of an 18-month-old child with regression of attained developmental milestones as a manifestation of HIV encephalopathy. This is the first such report in Indian literature. Commencing antiretroviral therapy in this child resulted in arrest of further regression of milestones. This alerts pediatricians to be aware that early developmental delay and regression may be a presenting manifestation of HIV infection in a child.

Antiretroviral drugs in the treatment of people living with human immunodeficiency virus: experience in a south Indian tertiary referral centre.

OBJECTIVE: A decrease in the number of new acquired immunodeficiency syndrome (AIDS) cases and AIDS--related deaths was seen in developed countries since 1996 due to the use of new combination of antiretroviral drugs. This retrospective study discusses the use of antiretroviral drugs in the treatment of people living with human immunodeficiency virus (HIV) in a developing country setting. METHODS: A retrospective case note analysis was done of patients receiving antiretroviral therapy at YRG Centre for AIDS Research and Education between Aug. 1996 and Feb. 1999. Out of 936 persons with HIV treated at this centre, 6.1% of the patients were prescribed three groups of drugs: Group A was the combination of the reverse transcriptase inhibitors (nRTI) zidovudine 600 mg daily and lamivudine 300 mg daily, Group B was the combination of zidovudine 600 mg daily, lamivudine 300 mg daily with protease inhibitor (PI) ritonavir 1200 mg daily and Group C was the combination of zidovudine 600 mg daily and lamivudine 300 mg daily with indinavir 2400 mg daily. Twenty HIV positive pregnant women were given zidovudine 500 mg daily during the third trimester (Group D) to reduce the vertical transmission of HIV. RESULTS: The mean CD4 gain was 188.0 cells/micro litre in Group A, 118.8 cell/microlitre in Group B and 223.3 cells/microlitre in Group C with a mean duration of 4.3, 3.1 and 3.5 months respectively. Many patients stopped antiretroviral drugs due to high cost of therapy. CONCLUSION: Hence, physicians should prescribe antiretroviral drugs only after ensuring that the patients can afford and will comply with a longterm treatment. Prescribing guidelines should be available to those working in this field and should be adhered to so that emergence of resistant strains could be prevented.

Identification of Pneumocystis carinii in induced sputum of AIDS patients in Chennai (Madras).

Induced sputum samples were collected from 32 AIDS patients with respiratory ailments. Pneumcystis carinii was demonstrated in 9 out of 32 AIDS cases by Indirect Immunofluorescence technique (HF). Four cases were positive by all the three techniques namely Giemsa staining, Toluidine blue staining and IIF, three were positive by both toluidine blue and IIF, and two were positive only by IIF. Among other microbial pathogens, acid fast bacilli was demonstrated in all the P carinii positive cases and Candida albicans in 53% AIDS cases from the induced sputum sample.