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Commercial HIV-1 genotypic resistance assays are very expensive, particularly for use in resource-constrained settings like India. Hence a cost effective in-house assay for drug resistance was validated against the standard ViroSeq™ HIV-1 Genotyping System 2.0 (Celera Diagnostics, CA, USA). A total of 50 samples were used for this evaluation (21 proficiency panels and 29 clinical isolates). Known resistance positions within HIV-1 protease (PR) region (1–99 codons) and HIV-1 reverse-transcriptase (RT) region (1–240 codons) were included. The results were analysed for each codon as follows: (i) concordant; (ii) partially concordant; (iii) indeterminate and (iv) discordant. A total of 2750 codons (55 codons per patient sample × 50 samples) associated with drug resistance (1050 PR and 1700 RT) were analysed. For PR, 99% of the codon results were concordant and 1% were partially concordant. For RT, 99% of the codon results were concordant, 0.9% were partially concordant and 0.1% were discordant. No indeterminate results were observed and the results were reproducible. Overall, the in-house assay provided comparable results to those of US FDA approved ViroSeq™, which costs about a half of the commercial assay ($ 100 vs. $ 230), making it suitable for resource-limited settings.

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.

HIV-infected children in resource-limited settings are increasingly gaining greater access to highly active antiretroviral therapy (HAART) but documented longitudinal data remains limited. We aimed to study the clinical and immunological outcomes among 67 South Indian HIV-infected children with18 months of follow-up on HAART at a tertiary HIV care program. The median CD4 cell count at enrolment was 290 cells microl(-1) and at treatment initiation was 225 cells microl(-1). Patients demonstrated a significant rise in their CD4 cell counts between treatment initiation and after 6 months (701 cells microll(-1); p = 0.007), 12 months (741 cells microl(-1); p = 0.037), and 18 months of therapy (718 cells microl(-1); p = 0.005). The most common adverse events to therapy were nausea (20.9%) and rash (25.4%). Over one-fifth of patients (25.4%) substituted therapy due to toxicities and 19.4% of patients switched to second-line protease inhibitor-containing regimens. In this South Indian pediatric cohort, generic HAART was safe, effective and relatively well tolerated.

Sexually transmitted infections (STIs) have been identified as cofactors of HIV transmission. Greater understanding of local STI burdens can assist in the development of more effective STI and HIV prevention strategies. The aim of this study is to determine the prevalence and incidence of STIs among South Indian men and women identified to be at increased risk for HIV infection. Individuals at increased risk for HIV infection were enrolled in a prospective longitudinal study in Chennai, India (n = 480) between August 2002 and December 2003. Participants were enrolled from patients seeking services at an sexually transmitted disease (STD) clinic and a confidential HIV testing and counseling program. The most common prevalent STIs were herpes simplex virus (HSV)-2 (50% of women, 29% of men), syphilis (11% of women, 8% of men), and Trichomonas vaginalis (6% of women). At enrollment, women, participants with no schooling, participants with greater than four sex partners, and single participants were found to be at increased risk for HSV-2 infection (p < 0.05). The two most common incident STIs at 12 months were HSV-2 with 12% of men and 8% of women testing positive and hepatitis B with 2% of men and 5% of women testing hepatitis B surface antigen (HBsAg) positive. In this cohort of South Indian men and women with a high background prevalence of HSV-2, suppressive therapy against herpes replication may have a substantial impact in reducing both HSV-2 transmission and HIV acquisition. With the high incidence of STIs, targeted prevention and clinical management strategies among individuals practicing high risk behaviors may help to slow the continued spread of HIV in 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 CD4200 cells/mm(3) at six and 12 months after randomisation. Secondary end-points were effective viral suppression (PVL400 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 PVL400 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 CD4200 cells/mm(3). One participant on CT and two on SIT had sustained PVL400 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.

The advent of highly active antiretroviral therapy (HAART) has changed the scenario of human immunodeficiency virus (HIV) infection. HIV patients in India have now access to generic HAART and this is the first report describing oral lesions in patients on HAART from our country. Oral lesions were studied in HIV seropositive patients (n = 50 on HAART and n = 50 not on HAART) attending a tertiary HIV referral care centre in India and patients on HAART were followed up. There was a difference in the occurrence of oral candidiasis (OC) between HAART and non-HAART participants (8% 24%; P 200 pigmentation was 43.8% in the HAART group and 14.8% in the non-HAART group (P < 0.05). The prevalence of OC in patients who had access to HAART was less when compared with those who did not have access to HAART. (authors)

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. 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. 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. 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. (authors)

Objective Combination antiretroviral therapy (ART) has improved in efficacy, durability and tolerability. Virological efficacy studies in India are limited. We determined incidence and predictors of virological failure among patients initiating first-line ART and described virological resuppression after confirmed failure, with the goal of informing national policy. Methods Therapy-naive patients initiated on first-line ART as per national guidelines were monitored every 3 months for adherence and virological response over 2 years. Genotyping on baseline samples was performed to assess primary drug resistance. Multivariate Cox regression analysis was used to assess predictors of virological failure. Results Virological failure rate among 599 eligible patients was 10.7 failures per 100 person-years. Cumulative failure incidence was 13.2% in the first year and 16.5% over 2 years. Patients initiated on tenofovir had a significantly lower rate of virological failure than those on stavudine or zidovudine (6.7 vs. 11.9 failures per 100 person-years, P = 0.013). Virological failure was independently associated with age

Background Children living with HIV have higher-than-normal prevalence of anemia. The beneficial effect of therapeutic iron has been questioned in the setting of high prevalence of infections. This study examines anemia prevalence and effect of standard therapeutic iron on HIV disease progression among children. Methods Perinatally-infected children aged 2–12 years were enrolled at three sites in southern India, and were followed for 1 year with clinical assessments, dietary recall and anthropometry. Laboratory parameters included iron markers (ferritin, soluble transferrin receptor) and other micronutrient levels (vitamin A, B12, folate). Iron was given to anemic children based on WHO guidelines. Statistical analyses including frequency distributions, chi square tests and multivariate logistic regression were performed using Stata v13.0. Results Among 240 children enrolled (mean age 7.7 years, 54.6 % males), median CD4 was 25 %, 19.2 % had advanced disease, 45.5 % had malnutrition, and 43.3 % were on antiretroviral treatment (ART) at baseline. Anemia was prevalent in 47.1 % (113/240) children. Iron deficiency was present in 65.5 %; vitamin A and vitamin B12 deficiency in 26.6 % and 8.0 % respectively; and anemia of inflammation in 58.4 %. Independent risk factors for anemia were stunting, CD4

Introduction: Given the chronic nature of HIV infection and the need for life-long antiretroviral therapy (ART), maintaining long-term optimal adherence is an important strategy for maximizing treatment success. In order to understand better the dynamic nature of adherence behaviors in India where complex cultural and logistic features prevail, we assessed the patterns, trajectories and time-dependent predictors of adherence levels in relation to virological failure among individuals initiating first-line ART in India. Methods: Between July 2010 and August 2013, eligible ART-naive HIV-infected individuals newly initiating first-line ART within the national program at three sites in southern India were enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical, laboratory and adherence parameters. Every three months, medication adherence was measured using pill count, and a structured questionnaire on adherence barriers was administered. Optimal adherence was defined as mean adherence ≥95%. Statistical analysis was performed using a bivariate and a multivariate model of all identified covariates. Adherence trends and determinants were modeled as rate ratios using generalized estimating equation analysis in a Poisson distribution. Results: A total of 599 eligible ART-naive patients participated in the study, and contributed a total of 921 person-years of observation time. Women constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3. Overall mean adherence among all patients was 95.4%. The proportion of patients optimally adherent was 75.6%. Predictors of optimal adherence included older age (≥40 years), high school-level education and beyond, lower drug toxicity-related ART interruption, full disclosure, sense of satisfaction with one’s own health and patient’s perception of having good access to health-care services. Adherence was inversely proportional to virological failure (IRR 0.55, 95%CI 0.44-0.69 p

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 (p0.001) 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 (p0.001) and increasing trends for admissions due to extra pulmonary tuberculosis (p0.01), toxoplasmosis (p0.01), Pneumocystis carinii pneumonia (p=0.02) and anemia (p0.001). 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.

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.

The objective of this study is to estimate the medical and non-medical out-of-pocket expenditure on care and support services to PLHA, the financial burden on households, the indirect costs and coping strategies to meet the financial burden. A structured pre-tested questionnaire was used to collect data from a cohort of 153 clients of YRG CARE, a leading Chennai based NGO, who had completed the first and third waves of interview during 2000/01 and 2001/02 respectively. The results show that the median out-of-pocket medical and non-medical expenditures (direct cost) for treatment and services are Rs. 6,000 (US $ 122) in a reference period of six months. Clients on antiretroviral (ARV) drugs spend five times more than those not on ARV. The median direct cost significantly increases with stage of disease, household income, and poverty level. The financial burden of treatment, measured as the ratio of direct cost to household income, is greater on lower income (82%) than on higher income (28%) households. 31% and 45% of the clients reported loss of income and workdays respectively. In conclusion, the direct costs and financial burden of care and support services increase with the stage of disease. The financial burden is disproportionately more on low-income households. HIV/AIDS leads to depletion of savings and increases the indebtedness of households.

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

Antiretroviral therapy (ART) for HIV is increasingly being introduced and utilized in diverse areas of the world. However, little research exists on adherence to ART in different cultural settings, particularly in developing countries such as India. This formative qualitative study examined barriers and facilitators of ART adherence among 60 (49 men, 11 women; 33 taking ART, 27 not currently taking ART) patients receiving HIV primary care at YRG CARE, a nongovernmental organization, in Chennai, India. The average participant reported becoming HIV infected through heterosexual transmission, was between 31 and 40 years old, had over ninth class standard education, was married, and generally had access to medical care; however, we obtained some qualitative data from various other risk categories. Trained ethnographers at the study site conducted in-depth interviews in the local language. These interviews were analyzed for content and ethnographic data. Almost all of the participants discussed the cost of ART as a barrier, with many reporting extended drug holidays, turning to family and/or friends, or taking drastic measures (i.e., selling family jewels, property) for financial assistance. Other barriers centered on privacy and stigma issues, such as disclosure of HIV inhibiting pill-taking and social support. Frequently discussed facilitators of adherence included perceived benefits of ART and proper adherence, perceptions about the consequences of nonadherence, and social support, if available. These data highlight the importance of reducing the cost of antiretroviral medications, involving family members in HIV care, and addressing privacy issues and stigma in counseling interventions in this setting.

We studied HIV prevalence in couples in Chennai, India. In 56% both partners were infected. Among discordant couples, 35 men and seven women were infected. Heterosexual intercourse is the primary risk factor. Concordance was related to sex with commercial sex workers for men and to genital ulcer disease for women. Median CD4 count was 97 cells/mm3 among concordant men, 222 cells/mm3 among discordant men. Condom use increased, and frequency of sexual intercourse decreased, among all couples after HIV diagnosis.

Background: A major obstacle to the administration of highly active antiretroviral therapy (HAART) in resource-limited settings is the high cost of CD4 count testing. The total lymphocyte count (TLC) has been proposed as a surrogate marker to monitor immune response to therapy. Objective: To assess, in a developed country setting, the capability and clinical utility of TLC change as a surrogate marker for CD4 count change in monitoring patients on HAART. Methods: Longitudinal co-variation between changes in TLC and concomitant changes in CD4 count following the initiation of HAART was examined using a retrospective cohort study of 126 HIV-positive patients attending The Miriam Hospital, Brown University, Providence, Rl. Analyses included evaluation of the direction of TLC change as a marker for direction of CD4 change, using sensitivity and specificity; evaluation of absolute change in TLC as a marker for benchmark changes in CD4 (≥50 over 6 months, ≥100 over 12 months), using receiver-operator characteristic (ROC) curves; and a regression model of change in TLC as a function of change in CD4, to understand within-individual variation of longitudinal TLC measures. Results: In the first 24 months of HAART, the sensitivity of a TLC increase as a marker for CD4 count increase over the same time period ranged from 86-94%, and the specificity ranged from 80-85%. The median change in TLC among patients with a CD4 count rise of ≥100 cells/mm 3 at 1 year of HAART was +766 cells/mm 3 while that of patients with a CD4 count rise of

There are few reports of the natural history of human immunodeficiency virus (HIV) infection from Asia. In a retrospective analysis of 594 patients (72.9% male; baseline CD4 cell count, 216 cells/microL) receiving care at YRG Center for AIDS Research and Education, a tertiary HIV referral center in southern India, the mean duration of survival from serodiagnosis was 92 months. Ninety-three percent of the patients acquired infection through heterosexual contact. The most common acquired immune deficiency syndrome-defining illnesses were pulmonary tuberculosis (49%; median duration of survival, 45 months), Pneumocystis carinii pneumonia (6%; median duration of survival, 24 months), cryptococcal meningitis (5%; median duration of survival, 22 months), and central nervous system toxoplasmosis (3%; median duration of survival, 28 months). Persons with a CD4 lymphocyte count of200 cells/microL were 19 times (95% confidence interval [CI], 5.56-64.77) more likely to die than were those with CD4 cell count of350 cells/microL. Patients who hador =1 opportunistic infection were 2.6 times more likely to die (95% CI, 0.95-7.09) than were those who did not have an opportunistic infection. Antiretroviral therapy for patients with low CD4 lymphocyte counts improved the odds of survival (odds ratio, 5.37; 95% CI, 1.82-15.83).

Background Mycobacterium avium–intracelllulare complex (MAC) prophylaxis is recommended for patients with CD4 counts of < 50 cells/mm3. With the significant decrease in incidence of disseminated MAC infection and the effective immune recovery due to the availability of combination antiretroviral therapy (ART), the benefits of giving MAC prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART. Methods TREAT Asia HIV Observational Database (TAHOD) patients aged ≥18 years with a CD4 count < 50 cells/mm3 at ART initiation were included. The effect of macrolide prohylaxis on HIV-associated mortality or an AIDS event (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted to assess whether results were consistent in patients with a CD4 < 100 cells/mm3 at ART initiation. Results Of 1,345 eligible patients (78% male with median age at ART initiation of 34.8 years), 10.6% received macrolide prophylaxis. The rates of the combined outcome and HIV-associated mortality per 100 patient years were 7.35 [95% confidence interval (CI): 6.04–8.95] and 3.14 (95% CI: 2.35–4.19), respectively. After adjusting for possible confounders, macrolide use was associated with a significantly decreased risk of HIV-associated mortality (HR 0.10, 95% CI: 0.01–0.80, P = 0.031) but not the combined outcome (HR 0.86, 95% CI: 0.32–2.229, P = 0.764). Sensitivity analyses showed that, among patients with a CD4 < 100 cells/ mm3 at ART initiation, these results were consistent. Conclusion Macrolide prophylaxis is associated with significantly improved survival among Asian HIV-infected patients with very low CD4 cell counts. The benefits of giving macrolide prophylaxis remain despite the availability of effective ART. Disclosures All authors: No reported disclosures.

Genital lesions are common in HIV positive patients and aetiology for these are mainly due to HSV, HPV or bacterial. They usually respond to HAART, antiviral or antimicrobials. We are presenting a young patient on HAART with non-healing genital ulcer lesions for sixteen months. He responded well to a change in ART regimen within a period of 15 days. This happened after a change to a more potent ART regimen.

The celebrities have the capacity to attract the attention of the audience and thereby indirectly influence the customers to enhance the sale of a product. It is a powerful communication force and a vital marketing tool helping to create awareness. The star appeal however needs to be perfectly blended intelligently and strategically to reap the benefits and make brands. The cause and effect relationship between celebrity endorsement and brand loyalty is analyzed. The aim of the study is to assess consumer’s perception regarding to use celebrity endorsement in advertisements. The Indians idolize their favorite actors and cricketers. The sample size is 200 were collected from male and female attitude towards celebrity advertisement. The celebrity advertisement could be more effective provided it is featured in television media that too in musical channel. The result of the study leads to the conclusion that the perception towards celebrities is positive.

Background The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections. Methodology/Principal Findings To assess the influence of pre-existing Wuchereria bancrofti infection on HIV progression, we performed a case-controlled treatment study of HIV positive individuals with (FIL+) or without (FIL-) W. bancrofti infection. Twenty-eight HIV+/FIL+ and 51 matched HIV+/FIL- subjects were treated with a single dose of diethylcarbamazine and albendazole (DEC/Alb) and followed for a year at regular intervals. Sixteen of the HIV+/FIL+ subjects (54%) and 28 of the HIV+/FIL- controls (57%) were on antiretroviral therapy (ART) during the study. Following treatment, no differences were noted in clinical outcomes between the 2 groups. There also was no significant difference between the groups in the HIV viral load at 12 months as a percentage of baseline viral load (HIV+/FIL+ group had on average 0.97 times the response of the HIV+/FIL- group, 95% CI 0.88, 1.07) between the groups. Furthermore, there were no significant differences found in either the change in viral load at 1, 3, or 6 months or in the change in CD4 count at 3, 6, or 12 months between the 2 groups. Conclusions/Significance We were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas. Trial Registration ClinicalTrials.gov NCT00344279, Author Summary In people living with HIV infection, simultaneous infections can adversely affect HIV disease. This has been seen with bacterial (tuberculosis), viral (cytomegalovirus), and parasitic infections (toxoplasmosis). Lymphatic filariasis is caused by a thin thread-like parasite that lives in the lymph vessels of infected people. It can cause significant disability. This infection is found in much of the same areas that high levels of HIV infection. We were interested in knowing if lymphatic filariasis changed the course of HIV infection in people with both diseases. In this study, the authors enrolled people in India who were living with HIV who either had or didn’t have filarial infection. All patients were treated for filariasis with 2 drugs, and then were followed for 1 year to see how their HIV disease progressed. No difference in HIV disease progression was found between the groups that did or did not have filariasis before treatment. The patients with HIV did well with the medicine for filariasis.

A total of 46 strains of Candida were collected from HIV infected patients, of which 25 strains were isolated from patients with oral candidiasis, and 21 strains were from mouthwash samples of asymptomatic carriers. The most common species isolated was Candida albicans (73.9%), followed by Candida tropicalis (21.7%). In vitro susceptibility of the strains to fluconazole and itraconazole was tested using minimum inhibitory concentration (MIC) studies by agar dilution technique. Out of the 18 strains of C. albicans isolated from mouthwash samples, four were resistant to fluconazole whereas only two were resistant to itraconazole. Out of 16 strains of C. albicans isolated from oral lesions, one was resistant to fluconazole where as all were sensitive to itraconazole. Among the other species of Candida tested, C. tropicalis gave higher MIC values to both drugs than other species such as Candida guillermondii and Candida krusei. In vitro MIC values correlated well with in vivo responses in patients. Hence, itraconazole may be used as an alternative in the treatment of candidiasis, which does not respond to fluconazole therapy.

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.

The spectrum of ocular lesions in children with HIV infection is different from that seen in adults. Ocular lesions in pediatric AIDS patients have not been studied in India. We analyzed the clinical profile, demographic characteristics, ocular and systemic lesions in children with AIDS seen in a referral eye institute in India. The clinical profile and demographic features were studied and complete ocular examination was done. Systemic findings were evaluated at an AIDS care center and recorded in a precoded proforma. Out of the 218 cases of HIV infection seen at our hospital between December 1993 and October 1999, 12 (5.50%) were below 15 years of age. Seven (58.33%) were males and 5 (41.66%) were females with the mean age of 6.5 years and median age of 6.2 years. Vertical transmission was the most common mode of infection (58.33%). Seven (58.33%) of these patients had systemic infection, the most common being pulmonary tuberculosis (42.85%). Ocular lesions were found in 6 (50%) patients. The most common ocular lesions were anterior uveitis and cytomegalovirus retinitis (CMV) (33%) followed by retinal detachment (16.66%) and vitreous hemorrhage (16.66%). High prevalence of ocular lesions in pediatric AIDS patients in India in a referral eye centre was observed. The most common lesions were anterior uveitis followed by CMV retinitis. The management in such cases was often challenging in a developing country like India.

PURPOSE: To document the ocular disorders seen in patients known to be infected with human immunodeficiency (HIV) virus at a referral eye clinic in India. METHODS: The first 100 individuals known to be HIV-positive at a referral eye clinic between 1993 and 1998 were enrolled in a prospective study. They underwent complete ocular and systemic evaluation. RESULTS: Most of the patients (76%) were in the 20- to 40-year age group. Heterosexual exposure to commercial sex workers was the most common risk factor. See also pp. 1–8. (70%) for HIV infection. Cytomegalovirus (CMV) retinitis (17%) and HIV retinopathy (15%) were the most common HIV-associated ophthalmic lesions. Pulmonary tuberculosis (67%) and oropharyngeal candidiasis (66%) were the most commonly associated systemic infections. Ocular involvement was most common in children who contracted the disease through perinatal transmission (66.7%) and in homosexual patients (60%). Ocular involvement was comparatively less common in patients who contracted the disease through blood transfusions (33%) or exposure to commercial sex workers (24.3%). CONCLUSIONS: This study shows that the spectrum of ocular lesions associated with HIV infection in India is different from that seen elsewhere in the world. The prevalence of CMV retinitis and HIV retinopathy is lower in India, and there have been no cases of ocular Kaposi sarcoma. Adnexal infections, albeit rare, were seen in our series. The nonavailability and cost of therapy influenced the visual prognosis in these patients.

Highly active antiretroviral therapy (HAART) has changed the face of human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS) by leading to dramatic decreases in HIV-related morbidity and mortality in the developed as well as developing world. Since the introduction of HAART, the incidence of ocular opportunistic infections causing retinitis has dramatically decreased, and clinicians should be aware of changes in the clinical presentation of ocular manifestations of HIV. As studies of HIV disease after the introduction of HAART continue to become available, more thorough descriptions of treated patients with ocular opportunistic infections will include side-effects and toxicities of therapy. This review focuses on the impact of HAART on the ocular manifestations of HIV.

Over the past decade, an increasing number of opportunistic fungal infections have been reported in immunocompromised subjects. Microascus spp. and their anamorphs Scopulariopsis spp. have been recovered from a wide geographical range. We report a case of Scopulariopsis brumptii in a 27-year-old man with AIDS presenting with breathlessness, pericardial effusion and hydrothorax in Chennai, southern India, in February 2007. Because of respiratory arrest, the patient was intubated. However, the patient developed obstructive shock and died due to cardiac dysfunctions. This report underlines the need for a direct, intensive approach to investigations in immunocompromised patients, especially those with AIDS.

The World Health Organization recommends the use of generic nevirapine (NVP)/efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens as first-line therapy in the management of HIV in resource-limited settings. Initiating NVP-based HAART at elevated CD4 cell counts can lead to liver toxicity. Short-term risk of liver toxicity has been reported in men with CD4 counts greater than 400 cells/mL and in women with CD4 counts greater than 250 cells/mL. Hence clinicians are advised to monitor the results of liver chemistry tests closely in the first 18 weeks of therapy because of the potential to develop life-threatening hepatic events. Mocroft et al showed that initiating NVP therapy at elevated CD4 levels may be safe for use in antiretroviral-experienced patients. Little is known about short-term adverse consequences and clinical outcome at elevated CD4 cell counts in a resource-limited setting. (authors)

BACKGROUND Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings. METHODS This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/ efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups. RESULTS Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1-13.1), his- tory of diabetes (OR, 10.7; 95% CI, 2.1-55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7-5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis, P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001). CONCLUSIONS TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study.

HIV and AIDS treatment in North America and Europe was revolutionized by the use of triple combination ART which resulted in dramatic decreases in morbidity and mortality. As the potency adverse effects and ease of ART administration continue to improve HIV is becoming more and more manageable within the developed world. The hallmark of triple combination ART has been profound suppression of viral load to undetectable levels (

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.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.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.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 (P0.001).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.

Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen.We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463.We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal.The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy.University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.

Background Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the safety of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD) were included in this analysis if they started combination antiretroviral therapy (cART) after 2002, were being treated at a center that documented a median rate of viral load (VL) monitoring ≥ 1 tests/patient/year, and experienced a minor or major treatment substitution while on virally suppressive cART (VL < 200 copies/mL). Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. Virologic failure was defined as having had two viral load measurements > 400 copies/mL. The patterns of substitutions and rate of virologic failure after substitutions were analyzed. Results Of 3,994 adults who started ART after 2002, 3,119 (78.1%) had at least one period of virological suppression. Among these, 1,170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of virological failure were 1.48/100person years (95% CI 1.14–1.91) in the minor substitution group and 2.85/100person years (95% CI 1.88–4.33) in the major substitution group, and 2.53/100person years (95% CI 2.20–2.92) among patients that did not undergo a treatment substitution. Conclusion The rate of virological failure was relatively low in both major and minor substitution groups, showing that regimen substitution is generally safe in non-clinical trial settings in Asian countries. Disclosures All authors: No reported disclosures.

This paper describes the incidence of immune reconstitution syndrome (IRS) from the developing world and implications for clinicians. Eleven of 144 HIV and tuberculosis (TB)-coinfected individuals followed for 72 person-years developed IRS within 6 months of initiating generic highly active antiretroviral therapy (HAART). All of the IRS patients were male, with a median age of 29 years; median CD4 at HAART initiation was 123 cells/mm3, and 6-month median CD4 rise was 124 cells/mm3. There was no statistical difference in CD4 rise or CD4 count and duration of TB treatment at HAART initiation between those who did and those who did not develop IRS (P = 0.8380). The median time to development of clinical IRS was 42 days (range 10-89 days). The incidence of IRS in this cohort is 15.2 cases per 100 patient-years. With increased coprevalence of opportunistic infections, especially TB, and increasing access to antiretroviral therapy in the developing world, clinicians in these countries must be able to identify IRS and relieve symptoms without compromising clinical care.

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings.

Introduction: The current study examines the spectrum of malignancies among HIV-infected South Indians enrolled in a clinical care program. Materials and Methods: We conducted a nested matched case-control study among 42 HIV-infected cases who developed cancer and 82 HIV-infected controls between 1998 and 2008 at a tertiary care HIV care program in South India. Results: The most common types of cancer included non-Hodgkin's lymphoma (38.1%), Hodgkin's lymphoma (16.7%), squamous cell carcinoma (14.3%), and adenocarcinoma (14.3%). The median duration of time from HIV infection to cancer diagnosis was 549 days [interquartile range (IQR): 58-2013]. The nadir CD4 cell count was significantly lower in cases compared to controls (134 cells/μl vs. 169 cells/μl; P = 0.015). Cancer patients were more likely to have a more advanced HIV disease stage at the time of cancer diagnosis compared to control patients (Stage C: 90.5% vs. 49.4%; P

Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies.

AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings.Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations.The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P.05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P.10). Significant country effects were noted on all NP tests and neurological outcomes (P.01).The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction.NCT00096824.

Background Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings. Methods Baseline characteristics from a randomized clinical trial of treatment-naive subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analysed to determine if there were significant differences by sex. Results Of the 1,571 participants, 740 (47.1%) were women. Women had higher mean screening CD4+ T-cell counts (mean 15 cells higher; P10 versus 5.05 log10 copies/ml; P+ T-cell count; however, it was independent of country and persisted within the strata with CD4+ T-cell count 3. Conclusions Women in resource-limited settings have lower levels of plasma HIV-1 RNA and appear to present for enrolment into clinical trials at an earlier stage of disease than men. The biological basis for lower viral load in women compared to men remains unexplained. It will be important to determine if the sex differences observed at baseline impact clinical outcomes once the PEARLS clinical trial is completed.

Brain White Matter (BWM) is formed on nerve fibres (due to myelin coating) and it undergoes continuous changes with aging throughout the life of humans. This age-related morphology, however, also gets further modified when a subject is infected by a viral disease such as HIV. In the present study, textural variations in BWM specific to a set of control images vs. images of a HIV + subject are assayed via an algorithm based on the Grey Level Co-occurrence Matrix (GLCM); and the associated Haralick features that are extracted from the GLCM. The clinical images of the brain used in the study are gathered from the noninvasive technique of Diffusion Tensor Magnetic Resonance Imaging (DT MRI). Results observed in the images of normal (nonpathogenic) subjects show progressive changes in the image parameters with aging; whereas, a wider variation is observed in the relevant parameters of the images pertinent to pathogenic subjects who exhibit cognitive (or motor impairments) due to HIV infection. The findings of the proposed method are reasonably correlated with clinical diagnosis in two HIV+ cases.

The current study examines sexual behaviors among HIV-infected Indians in primary care, where access to highly active antiretroviral therapy (HAART) has recently increased. Between January to April 2008, we assessed the sexual behaviors of 247 HIV-infected South Indians in care. Multivariable logistic regression models were used to determine predictors of being in a HIV-seroconcordant primary relationship, being sexually active, and reporting unprotected sex. Over three-fourths (80%) of participants were HAART-experienced. Among the 58% of participants who were currently in a seroconcordant relationship, one-third were serodiscordant when first tested for HIV. Approximately two-thirds (63.2%) of participants were sexually active; 9.0% reported unprotected sex. In the multivariable analyses, participants who were in a seroconcordant primary relationship were more likely to have children, use alcohol, report unprotected sex, and have been enrolled in care for >12 months. Sexually active participants were more likely to be on HAART, have a prior tuberculosis diagnosis, test Herpes simplex type 2 antibody seropositive, and have low general health perceptions. Participants who reported unprotected sex were more likely to be in a seroconcordant relationship, be childless, want to have a child, and use alcohol. We did not document an association between HAART and unprotected sex. Among HIV-infected Indians in primary care, predictors of unprotected sex included alcohol use and desire for children. Prevention interventions for Indian couples should integrate reproductive health and alcohol use counseling at entry into care.