Validation of the D: A: D Chronic Kidney Disease Risk Score Model Among People Living With HIV in the Asia-Pacific.

BACKGROUND: We validated the Data collection on Adverse events of anti-HIV Drugs (D:A:D) full-risk and short-risk score models for chronic kidney disease (CKD) in the Asian HIV cohorts. SETTINGS: A validation study among people living with HIV (PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region. METHODS: PLHIV with a baseline estimated glomerular filtration rate > 60 mL/min/1.73 m were included for validation of the D:A:D CKD full version and short version without cardiovascular risk factors. Those with <3 estimated glomerular filtration rate measurements from baseline or previous exposure to potentially nephrotoxic antiretrovirals were excluded. Kaplan-Meier methods were used to estimate the probability of CKD development. The area under the receiver operating characteristics was also used to validate the risk score. RESULTS: We included 5701 participants in full model {median 8.1 [interquartile range (IQR) 4.8-10.9] years follow-up} and 9791 in short model validation [median 4.9 (IQR 2.5-7.3) years follow-up]. The crude incidence rate of CKD was 8.1 [95% confidence interval (CI): 7.3 to 8.9] per 1000 person-years in the full model cohort and 10.5 (95% CI: 9.6 to 11.4) per 1000 person-years in the short model cohort. The progression rates for CKD at 10 years in the full model cohort were 2.7%, 8.9%, and 26.1% for low-risk, medium-risk, and high-risk groups, and 3.5%, 11.7%, and 32.4% in the short model cohort. The area under the receiver operating characteristics for the full-risk and short-risk score was 0.81 (95% CI: 0.79 to 0.83) and 0.83 (95% CI: 0.81 to 0.85), respectively. CONCLUSION: The D:A:D CKD full-risk and short-risk score performed well in predicting CKD events among Asian PLHIV. These risk prediction models may be useful to assist clinicians in identifying individuals at high risk of developing CKD.

Reliability, Validity, and Factor Structure of the Internalized AIDS-Related Stigma Scale in Southern India.

We used data from 660 people living with HIV in southern India to evaluate the reliability, validity, and factor structure of the Internalized AIDS-Related Stigma Scale. Exploratory factor analysis revealed the presence of 2 factors: a 2-item factor related to disclosure concerns and a 4-item factor related to self-hatred. The self-hatred factor demonstrated acceptable internal consistency (Cronbach α = .80). As evidence of construct validity, both factors were correlated with depression symptom severity as measured by the Patient Health Questionnaire-9. Further study is needed to understand the correlates of these factors and their impact on the Indian HIV care continuum.

Safety, Tolerability, and Efficacy of Generic Dolutegravir-containing Antiretroviral Therapy Regimens Among South Indian Human Immunodeficiency Virus-infected Patients.

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.

Association between internalized stigma and depression among HIV-positive persons entering into care in Southern India.

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.

Broadly Neutralizing Antibody Responses in a Subset of HIV-1-Infected Individuals in Chennai, India.

Identification of broadly neutralizing antibodies (NAbs) generated during the course of HIV-1 infection is essential for effective HIV-1 vaccine design. The magnitude and breadth of neutralizing activity in the sera from 46 antiretroviral treatment-naive HIV-1 clade C-infected individuals was measured in a single round infection assay using TZM-bl cells and multisubtype panel of env-pseudotyped viruses. Higher levels of NAb response (NAb titer 500 to >40 000) were measured in these patients against tier 1 and tier 2 viruses. The average magnitude of the NAb responses of chronically infected individuals against heterologous viruses was consistently higher than the response observed from individuals with long-term nonprogressor ( P = .086). To conclude, high titers of HIV-1 cross-neutralizing activity were observed in the sera from a subset of HIV-1-infected individuals in Chennai, India. Additional studies of the epitopes recognized by these antibodies may facilitate the discovery of an effective vaccine immunogen.

Prevalence and correlates of psychosocial conditions among people living with HIV in southern India.

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 CSA and 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. Three hundred and eighty-three 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 (Adjusted Odds Ratio = 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.

The occurrence of Simpson's paradox if site-level effect was ignored in the TREAT Asia HIV Observational Database.

OBJECTIVES: In multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to "Simpson's paradox" (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models. STUDY DESIGN AND SETTING: Survival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site. RESULTS: A total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs. 0.61). Models (2)-(4) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models. CONCLUSIONS: Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.

TB-IRIS after initiation of antiretroviral therapy is associated with expansion of preexistent Th1 responses against Mycobacterium tuberculosis antigens.

BACKGROUND: The role of T-cell responses against Mycobacterium tuberculosis antigens in tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is unclear. METHODS: Peripheral blood mononuclear cells from 45 HIV patients with treated TB, of whom 12 developed TB-IRIS, were collected at weeks 0, 2, and 6 of antiretroviral therapy (ART). Production of interferon-gamma (IFN-γ) and interleukin-2 by T cells after stimulation with purified protein derivative (PPD) or early secretory antigenic target-6 (ESAT-6) and T-cell expressions of CCR5 and CXCR3 were assessed by flow cytometry. IFN-γ and CXCL10 were assayed by enzyme-linked immunosorbent assay. RESULTS: TB-IRIS patients had higher proportions of PPD- and ESAT-6-reactive IFN-γ⁺CD4⁺ and CD3⁺CD4⁻ T cells at weeks 0, 2, and 6. IFN-γ levels were also higher in peripheral blood mononuclear cell culture supernatants at all times with PPD but only at weeks 2 and 6 with ESAT-6. There were few differences for interleukin-2. CXCL10 levels in supernatants after PPD and ESAT-6 stimulation were only higher at week 6. CXCR3⁺/CCR5⁺CD4⁺ T cells were higher at week 2, and CCR5⁺CD4⁺ T cells were higher at week 6. CONCLUSIONS: TB-IRIS is associated with Th1 responses against M. tuberculosis antigens by CD4⁺ and CD3⁺CD4⁻ T cells that are present before ART and amplified afterward. It is unclear if these cause immunopathology or reflect a high pathogen load.