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In India, many people living with HIV (PLHIV) do not successfully initiate antiretroviral therapy (ART) after diagnosis. We conducted a clinic-based qualitative study at the Y.R. Gaitonde Centre for AIDS Research in Chennai, Tamil Nadu to explore factors that influence ART non-initiation. We interviewed 22 men and 15 women; median age was 42 (IQR, 36–48) and median CD4+ was 395 (IQR, 227–601). Participants were distrustful of HIV care freely available at nearby government facilities. Faced with the perceived need to access the private sector and therefore pay for medications and transportation costs, non-initiators with high CD4+ counts often decided to postpone ART until they experienced symptoms whereas non-initiators with low CD4+ counts often started ART but defaulted quickly after experiencing financial stressors or side effects. Improving perceptions of quality of care in the public sector, encouraging safe serostatus disclosure to facilitate stronger social support, and alleviating economic hardship may be important in encouraging ART initiation in India.

Electronic Patient Reported Outcomes (PROs), which consist of questionnaires administered directly to patients via handheld device or computer, allow for the routine and systematic capture of sensitive domains as well as longitudinal data on functional status, symptom severity, and physical and psychological well-being. There have been few examples of PROs in HIV care in low- and middle-income countries (LMICs) and none in India. We conducted a study to assess the feasibility and acceptability of PROs at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, Tamil Nadu. We adapted an adherence and psychosocial questionnaire into an electronic PRO format and administered it to a convenience sample of 50 participants. Almost all participants indicated that the PRO questionnaire was easy to complete and understand (96%). The percentage who needed any staff help was 83% among illiterate participants but only 13% among literate participants (p

Background:Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.Objective:This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.Methods:HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.Results:Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.Conclusion:LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.

We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from genotypic data.

BackgroundDepression is highly prevalent in people living with HIV (PLHIV) and is associated with increased morbidity and mortality. In India, where access to mental health specialists is limited, little is known about the attitude of HIV clinicians toward depression in PLHIV.MethodsWe administered a questionnaire to HIV clinicians attending the 2015 Chennai Antiretroviral Therapy Symposium that assessed respondents' level of agreement with 29 statements regarding the etiology, importance, and management of depression and whether they felt capable and willing to manage depression in PLHIV.ResultsThe 69 respondents were from 9 Indian states. Most respondents agreed that depression in PLHIV is a serious problem (91%) and is associated with poorer HIV-related outcomes (62%-81%). Although most respondents (76%) reported feeling comfortable discussing mental health problems with PLHIV, almost half (48%) admitted that lack of knowledge and training about mental health issues hindered the diagnosis and treatment of depression in PLHIV. With few exceptions, there were no significant differences in responses by gender, urban/rural practice location, or government versus private practice.ConclusionsIndian HIV clinicians believe that depression in PLHIV is important and are willing to manage depression in the HIV primary care setting. These findings suggest that HIV clinicians require further training to deliver evidence-based interventions to treat PLHIV with depression.

In India, there is little evidence on reasons for high rates of loss to HIV care. We conducted a clinic-based qualitative study at the YR Gaitonde Centre for AIDS Research and Education to explore factors that influence loss to care. In all, 17 men and 14 women were interviewed; median age was 42 (interquartile range [IQR], 36-48) and median CD4 count was 448 (IQR, 163-609). A majority reported avoiding treatment freely available at nearby government facilities because of disclosure concerns and perceptions of poor quality. As a result, participants sought care in the private sector where they were subjected to medication and transport costs. Life circumstances causing lost wages or unexpected expenditures therefore prevented participants from attending clinic, resulting in loss to care. Improving perceptions of quality of care in the public sector, addressing disclosure concerns, and reducing economic hardships among people living with HIV may be important in reducing loss to HIV care in India.

In this first study of generic dolutegravir (DTG)-containing regimens in a low-resource setting, we assessed safety, tolerability, and efficacy within a prospective cohort of 564 patients with at least 6 months of clinical follow-up. We provide support for a large-scale transition to DTG as part of first-line regimens.

BACKGROUND: Little is known regarding barriers to hepatitis C virus (HCV) treatment among people who inject drugs (PWID) in low-resource settings, particularly in the era of direct-acting antiviral therapies. METHODS: Between March, 2015–August, 2016, a cross-sectional survey was administered to community-based PWID in Chennai, India to examine the HCV care continuum and associated barriers. Adjusted prevalence ratios (APR) were estimated by multivariable Poisson regression with robust variance. RESULTS: All participants were male (n=541); 152 participants had HCV mono-infection and 61 participants had HIV/HCV co-infection. Only one HCV mono-infected and one HIV/HCV co-infected participant was linked to HCV care. Overall, there was moderate knowledge of HCV disease but poor knowledge of HCV treatment. Higher total knowledge scores were negatively associated with HIV/HCV co-infection (vs. HCV mono-infection), though this was not statistically significant in adjusted analysis (APR=0.71[95%CI=0.47–1.06]). Participants ≥45 years (APR=0.73[95%CI=0.58–0.92]) and participants with HIV/HCV co-infection (APR=0.64[95%CI=0.47–0.87]) were less willing to take weekly interferon injections for 12 weeks. Willingness to undergo HCV treatment improved with decreasing duration of therapy, higher perceived efficacy, and use of pills vs. interferon, though willingness to use interferon improved with decreasing duration of therapy. Most participants preferred daily visits to a clinic for HCV treatment versus receiving a month’s supply. Participants ≥45 years (vs.

Background In India, which has the third largest HIV epidemic in the world, depression and HIV-related stigma may contribute to high rates of poor HIV-related outcomes such as loss to care and lack of virologic suppression. Methods We analyzed data from a large HIV treatment center in southern India to estimate the burden of depressive symptoms and internalized stigma among Indian people living with HIV (PLHIV) entering into HIV care and to test the hypothesis that probable depression was associated with internalized stigma. We fitted modified Poisson regression models, adjusted for sociodemographic variables, with probable depression (PHQ-9 score ≥10 or recent suicidal thoughts) as the outcome variable and the Internalized AIDS-Related Stigma Scale (IARSS) score as the explanatory variable. Findings 521 persons (304 men and 217 women) entering into HIV care between January 2015 and May 2016 were included in the analyses. The prevalence of probable depression was 10% and the mean IARSS score was 2.4 (out of 6), with 82% of participants endorsing at least one item on the IARSS. There was a nearly two times higher risk of probable depression for every additional point on the IARSS score (Adjusted Risk Ratio: 1.83; 95% confidence interval, 1.56-2.14). Conclusions Depression and internalized stigma are highly correlated among PLHIV entering into HIV care in southern India and may provide targets for policymakers seeking to improve HIV-related outcomes in India.

Background Addition of integrase strand transfer-inhibitors (mainly dolutegravir) has strengthened anti-retroviral therapy (ART), to sustain viral suppression in HIV-1 and 2-infected patients. For judicious use in the future, we examine weight gain in ART-naïve, and those exposed to INSTI-based regimens as first, second, and third-line ART. Methods We undertook a retrospective cross-sectional study of patients initiated on INSTI-based regimens from 15 January 2017 to 22 December 2018 (n = 333). Descriptive statistical analyses were performed using STATA 15.1. Cross-tabulation and stratification were conducted to measure the strength of association. A linear regression model was used to study the increase in weight per unit of time. Results 331 patients are infected with HIV-1 and 2 with HIV-2. 66% are male, median age= 38 years (IQR 31–44). Median CD4 count at INSTI initiation was 226 cell/cubic mL (IQR 87–395). Median viral load at initiation of INSTI-based therapy was log104.768 copies/mL (IQR 2.9—5.63). Most common opportunistic infections were pulmonary tuberculosis (n = 97), oral candidiasis (n = 84), and herpes zoster (n = 44). Median hemeoglobin was 12gm% (IQR 10.5–13.8). 39% were initiated on TDF+3TC+DTG and 32% were initiated on TDF+FTC+DTG. 74% experienced weight gain; average increase was 3.69 Kg (SD 3.56) at 3 months. 19.5% gained >4 kg; median BMI at initiation of therapy was 22.56 kg/m2 (IQR 19.8–25.1) and 25.4 kg/m2 (IQR 22.5–28.7) at an average of 9.5 months post initiation of dolutegravir-based ART. 70% of ART naïve (n = 73) experienced weight gain; 17.8% gained 8.36 kg at 9 months. Higher weight gain was observed in patients with opportunistic infections. Association with gender (OR = 0.9 95%, CI 0.54 -1.5; P = 0.70) and age (OR=0.9, 95% CI 0.97–1.01;P = 0.71) was not significant. Weight gain was positively correlated with time (r=+1); predicted increase in weight per 0.1 months after initiation of INSTI-based regimen (F=4.62, P = 0.032). Conclusion Access and adherence to INSTI have positively influenced viral suppression of HIV-infection.To ensure the prevention of obesity and apt use of ART for malnourished patients, it is imperative to monitor weight gain in patients who are initiated on INSTI-based regimens. Further research to study the mechanism of weight gain is warranted. Disclosures All authors: No reported disclosures.

Psychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third-largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for childhood sexual abuse (CSA) and intimate partner violence (IPV). We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. 383 persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (AOR=2.24, 95% CI, 1.04-4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.

Background: Neopterin, a metabolite of guanosine, belongs to the class of chemical compounds known as pteridines and is an early and valuable marker of cellular immunity. Recently, it was shown to be associated with the initiation and progression of periodontal disease. The aim of the present study was to assess the relationship between clinical parameters and concentrations of neopterin within gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites before and after the treatment of periodontitis. Methods: Sixty age (35 to 65 years)- and gender-matched (30 males and 30 females) subjects were recruited and divided into the following four groups of 15 subjects each based on gingival index, Ramfjord periodontal disease index, clinical attachment loss (CAL), and radiographic parameters (bone loss): healthy (group 1), gingivitis (group 2), mild periodontitis (group 3), and moderate to severe periodontitis (group 4). A fifth group consisted of the 15 subjects from group 4, 6 to 8 weeks after treatment (scaling and root planing). GCF was collected from each patient, and the neopterin levels were determined by enzyme immunoassay. Results were analyzed statistically. Results: The mean concentration of neopterin in GCF was the highest in group 4 (51 nmol/l) and the lowest in group 1 (1.36 nmol/l). The mean neopterin concentrations in group 2 (9.69 nmol/l) and group 3 (16.58 nmol/l) fell between the highest and lowest values. This suggested a positive correlation between CAL and GCF neopterin concentrations. Neopterin levels in group 4 decreased to 1.77 nmol/l after treatment (group 5). Conclusions: Neopterin increased in parallel with the severity of inflammatory disease. Its levels in GCF may be potentially useful as an indicator of periodontal inflammation and the host response.

SummaryObjectiveTo describe the causes of mortality among the HIV-infected in southern India in the era of highly active antiretroviral therapy (HAART).MethodsAnalyses of this patient cohort were conducted using the YRG Centre for AIDS Research and Education HIV Natural History Observational Database. Causes of death were then individually confirmed by patient chart review.ResultsSixty-nine deaths occurred within the inpatient unit; 25% were female and the median age of the 69 patients was 34 years. Over half of the patients (55%) died within three months of initiating HAART. At the time of enrollment into clinical care, the median CD4 cell count was 64 cells/μl (interquartile range (IQR) 37–134). At the time of initiating HAART, the median CD4 cell count was 58 cells/μl (IQR 31–67) for patients who died within 3 months of initiating HAART and 110 cells/μl (IQR 77–189) for patients who died more than 3 months after initiating HAART. Close to three-fourths of patients (70%) died from an AIDS-defining illness (ADI). The major ADI causes of death included Pneumocystis jiroveci pneumonia (22%), extrapulmonary tuberculosis (19%), CNS toxoplasmosis (12%), and pulmonary tuberculosis (10%). A tenth of patients died from cerebrovascular infarcts. Three patients (4%) died from non-Hodgkin lymphoma.ConclusionsAIDS-related events continue to be the major source of mortality among the HIV-infected in southern India in the era of HAART. This mortality pattern justifies increased proactive efforts to identify HIV-infected patients and initiate HAART earlier, before patients present to care with advanced immunodeficiency.

Leukotriene B(4) (LTB(4)) is a membrane-derived lipid mediator formed from arachidonic acid. LTB(4) is among the most potent stimulants of polymorphonuclear leukocytes (PMNs) and, thus, participates in tissue injury by recruiting PMNs in a pathophysiologic scenario of periodontal diseases. The aim of the present study was to assess the relationship between clinical parameters and concentrations of LTB(4) within gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites before and after the treatment of periodontitis.Sixty subjects were divided into three groups with 20 subjects in each group: healthy (group 1), gingivitis (group 2), and chronic periodontitis (group 3). Groups were based on periodontal disease index (PDI), clinical attachment loss (CAL), and radiographic evidence of bone loss. Group 4 consisted of the subjects in group 3 at 6 to 8 weeks after treatment, i.e., scaling and root planing (SRP). GCF samples collected from each patient were quantified for LTB(4) using an enzymatic immunometric assay. In addition, the correlation between in situ LTB(4) levels and clinical parameters was analyzed in each group.The highest mean LTB(4) concentration in GCF was observed in group 3 (185.2 pg/microl), and the lowest was observed in group 1 (39.6 pg/microl). Its level in group 3 decreased to 79.35 pg/microl after treatment (group 4). Further, GCF LTB(4) levels in all groups showed a statistically significant positive correlation with PDI and CAL (P0.005).The substantial increase in GCF LTB(4) concentrations with the severity of periodontal disease and a concomitant decrease in its level following SRP in subjects with periodontitis suggest a possible role for LTB(4) in the progression of periodontal disease.

Supplemental Material, IARSSIndia-JIAPAC_revised_Supplemental_material for Reliability, Validity, and Factor Structure of the Internalized AIDS-Related Stigma Scale in Southern India by Brian T. Chan, Amrose Pradeep, Ezhilarasi Chandrasekaran, Lakshmi Prasad, Vinothini Murugesan, Nagalingeswaran Kumarasamy, Kenneth H. Mayer, and Alexander C. Tsai in Journal of the International Association of Providers of AIDS Care (JIAPAC)

Supplemental Material, IARSSIndia-JIAPAC_revised_Supplemental_material for Reliability, Validity, and Factor Structure of the Internalized AIDS-Related Stigma Scale in Southern India by Brian T. Chan, Amrose Pradeep, Ezhilarasi Chandrasekaran, Lakshmi Prasad, Vinothini Murugesan, Nagalingeswaran Kumarasamy, Kenneth H. Mayer, and Alexander C. Tsai in Journal of the International Association of Providers of AIDS Care (JIAPAC)