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Background: Galectin-9 induces HIV reactivation and also contributes to non-AIDS events through inflammaging. Hence, it is important to assess its levels in HIV-infected individuals to determine their association with HIV viremia and other comorbidities., Methods: Plasma galectin-9 levels were estimated in viremic (n = 152) and aviremic ( n = 395) individuals on first-line antiretroviral therapy (ART). They were assessed for correlation with HIV-1 viral load (VL), CD4 count, and ART duration, as well as for receiver operating characteristic curve analysis., Result: Plasma galectin-9 levels correlated positively with VL (r = 0.507, p < 0.0001) and ART duration (r = 0.308, p = 0.002) and negatively with CD4 count (r = -0.186, p < 0.0001). Area under the curve for galectin-9/CD4 count ratio for identifying viremic individuals was 0.906. Sensitivity and specificity of the ratio at a cutoff of 14.47 were 90.13% and 70.05%, respectively, for detecting viremic individuals. Further, galectin-9 levels correlated with cystatin C (r = 0.239, p = 0.0183), IL-18 (r = 0.311, p = 0.006), and systolic blood pressure (r = 0.220, p = 0.0355). Galectin-9-induced HIV reactivation was significantly lower in individuals on long-term ART than those on short-term ART., Conclusion: The galectin-9-to-CD4 count ratio indicated the potential of galectin-9 as a cheaper monitoring tool to detect HIV viremia. Strategies for countering the effects of galectin-9 for controlling HIV viremia and non-AIDS events are urgently warranted.

Objectives: The effectiveness of lactobacilli-containing vaginal tablets (VT) in bacterial vaginosis (BV) recurrence prevention among women infected with HIV treated with standard oral metronidazole in Pune, India was studied., Methods: Women infected with HIV with confirmed BV diagnosis (Nugent score ≥7 and Amsel criteria >3) were enrolled in a 12-month, double-blind, randomized, placebo-controlled, phase IV study between 2018 and 2021. After a standard course of oral metronidazole for 7 days (400 mg three times a day), women were randomly assigned to either lactobacilli-containing or placebo VT arms to receive VTs for 4 months. BV recurrence was assessed after the initial cure from BV., Results: Of the 464 women infected with HIV, 80 women with confirmed BV were enrolled. The retention was affected due to the COVID-19 pandemic (6-month retention rates 78%). The cure was seen in 85% and 93.5% of participants from the treatment and placebo arms, respectively, after four VT cycles. BV recurrence was seen in 41.4% and 44.8% in the treatment and placebo arm, respectively, with no significant difference in the two groups., Conclusion: The lactobacilli-containing VT was acceptable and safe; however, the addition of VT over standard oral metronidazole did not show any additional benefit in the prevention of BV recurrence in women infected with HIV, indicating the need for long-term randomized trials among them. Registered at Clinical Trials Registry- India, (CTRI) Number: CTRI/2018/04/013298., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Most studies assessing drug resistant tuberculosis (DRTB) in human immunodeficiency virus (HIV) co-infected patients in India have used conventional culture- based systems to diagnose DRTB that have a longer turnaround time leading to risk of amplification of resistance to an empirical regimen. We determined the prevalence of DRTB amongst people living with HIV (PLHIV) using the line probe assay and determined risk factors associated with the presence of multi drug resistant tuberculosis (MDRTB)., Methods: A Cross-sectional study was undertaken at Poona Hospital and Research Center (PHRC) and the Institute of Infectious Diseases, two tertiary level private care centers in Pune, India. Consenting PLHIV with confirmed Pulmonary TB (PTB) and/or extra-pulmonary TB (EPTB) diagnosed based on detection of Mycobacterium TB by line probe assay (Geno Type MTBDRplus version 2) on clinical specimens were included. Those with documented past history of DRTB were excluded. Resistance against anti-TB drugs was determined by the same assay. The prevalence of any form of drug resistant TB (DRTB), MDRTB, Rifampicin resistant TB (RRTB) and Isoniazid (INH) mono-resistant TB were determined as the proportion of these amongst all included PLHIV-TB. A multivariate analysis was conducted to determine risk factors that were statistically associated with MDRTB, DRTB, RRTB and INH mono-resistant TB., Results: Two hundred PLHIV were recruited. The prevalence (95% CI) of MDRTB, INH mono- resistance and RR resistance was 12.5% (7.9-17.1%), 9% (6.9-11.2%) and 2.5% (1.4-3.6%), respectively. The prevalence (95% CI) of MDRTB among new and relapsed patients was 8.8% (6.5-11.1%) and 23.1% (17.2-28.9%), respectively. Tuberculosis relapse was the only factor significantly associated with MDRTB, DRTB and INH mono-resistant TB., Conclusion: We document a high prevalence of drug resistance to anti-TB drugs including MDRTB among PLHIV in our setting using Geno Type MTBDRplus directly on clinical specimens. This validates the WHO recommendation of performing routine rapid molecular resistance testing prior to initiating anti-TB treatment among all PLHIV with presumptive TB. Using rapid molecular testing especially Geno Type MTBDRplus (that detects resistance to INH and Rifampicin simultaneously) reduces the turn-around time helping in optimizing treatment.

Background: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings., Methods: A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure., Results: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p < 0.01), the linear regression showed a moderate fit (R 2  = 0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p = 0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R 2  = 0.896 to 0.982)., Conclusion: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent.Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6-6.8], 17.7 [95% CI 15.8-19.8], and 11.5 [95% CI 10-12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8-17.2] and 22.6 [95% CI 14.3-33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8-30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen.Our study demonstrates the feasibility of using probabilistic record-linkage to study cancer/other comorbidities among PLHIV in India and provides preliminary population-based estimates of cancer risks in PLHIV in India. Our results, suggesting a potentially substantial burden and slightly different spectrum of cancers among PLHIV in India, support efforts to conduct multicenter linkage studies to obtain precise estimates and to monitor cancer risk in PLHIV in India.

Background: Indian cultural tradition demanding marriage, many MSM howsoever they self-identify are likely to be married or have sex with women. To consolidate India's HIV prevention gains, it is important to understand and address the interaction between the MSM and heterosexual epidemics in India and create specific interventions for bisexual MSM. The challenge is to identify and intervene this hard to reach population. Data from HIV Sentinel Surveillance 2011 among MSM in four Indian states were analyzed to assess predictors and prevalence of bisexual behaviour in MSM., Methods: Between March-May 2011, 4682 men (15-49 years) who had anal/oral sex with a male partner in the past month, attending intervention sites and consenting for an un-linked anonymous survey answered an 11- item questionnaire and provided blood for HIV test by finger stick at 19 designated surveillance sites., Results: Of 4682 MSM tested overall, 5% were illiterate, 51% reported only receptive anal intercourse, 21% only penetrative and 28% both. 36% MSM had ever received money for sex. Overall 6.8% were HIV infected. 44% MSM were bisexual in the last six months. On multivariate analysis, 'being bisexual' was found to be independently associated with 'older age': 26-30 years [AOR = 3.1, 95% CI(2.7, 3.7)], >30 years [AOR = 6.5, 95% CI(5.5, 7.7)]; 'reporting penetrative behaviour alone' with other men [AOR = 5.8, 95% CI(4.8, 7.0), p<0.01] and 'reporting both penetrative and receptive behaviour' [AOR = 2.7, 95% CI(2.3, 3.1) p<0.01]. Those who both paid and received money for sex [AOR = 0.49, 95% CI (0.38, 0.62)] were significantly less likely to be bisexual., Conclusions: A substantial proportion of men receiving services from Targeted Intervention programs are bisexual and the easy opportunity for intervention in this setting should be capitalised upon. Focusing on older MSM, as well as MSM who show penetrative behaviour with other men, could help in reaching this population.

Introduction: Role of vaginal sex in heterosexual transmission of HIV has been investigated but that of heterosexual anal sex (HAS) is not fully understood. This paper examines practice of HAS among Female Sex Workers (FSWs) and its correlates in India where the HIV epidemic is being primarily driven by core groups like FSWs., Methods: Data for this paper are drawn from Round I survey of 9667 FSWs in the Integrated Biological and Behavioral Assessment (IBBA) from 23 districts of 4 high HIV prevalent states of India. Bivariate and multivariate analysis identified factors associated with HAS., Results: Ever having anal sex was reported by 11.9% FSWs (95% CI: 11.3%-12.6%). Typology (AOR 2.20, 95% CI 1.64-2.95) and literacy (AOR 1.28, 95% CI 1.10-1.49) were positively associated with practice of HAS. Longer duration in sex trade (AOR 1.69, 95% CI 1.44-1.99), entertaining larger number of clients the previous week (AOR 1.78, 95% CI 1.47-2.15), alcohol consumption (AOR 1.21, 95% CI 1.03-1.42) and inability to negotiate condom use (AOR 1.53, 95% CI 1.28-1.83) were also correlated with HAS. Self-risk perception for HIV (AOR 1.46, 95% CI 1.25-1.71) did not impede HAS. Although symptoms of sexually transmitted infections (STIs) in the last 12 months were associated with anal sex (AOR 1.39, 95% CI 1.13-1.72) there was no significant association between laboratory confirmed HIV and other STIs with HAS., Conclusion: Practice of HAS by FSWs might significantly contribute to HIV transmission in India. This study also shows that despite self-risk perception for HIV, even literate FSWs with longer duration in sex work report HAS. General messages on condom use may not influence safe HAS. FSWs need to be targeted with specific messages on HIV transmission during anal sex. Women controlled prevention methods, such as rectal microbicides and vaginal microbicides are needed.

Background: Diarrhea in HIV infected individuals is a common complication seen in about 90% of patients in developing countries. The objective of this study was to identify enteric pathogens in HIV infected and HIV uninfected individuals in Pune., Method: This study was conducted from January 2009 to May 2010 on 331 consecutive patients presenting with diarrhea admitted at Naidu Municipal Corporation Hospital, Pune and processed using conventional methods., Results: Intestinal parasitic pathogens were detected in 60% (39/65) of HIV infected and 14.3 (38/266) of HIV uninfected individuals. Bacterial pathogens were detected in 34% (22/65) of HIV infected individuals and 28.2% (75/266) of the HIV uninfected individuals. The common enteric pathogens detected in HIV infected individuals were Cystoisospora belli (28%, 18/65) followed by Cryprotosporidium parvum (12%, 8/65). In HIV uninfected individuals Entamoeba histolytica (7.1%, 19/266) followed by Shigella flexnari (4.9%, 13/266) were the most common pathogens. The difference in detection of enteric parasites in HIV infected individuals and HIV uninfected individuals was found to be significant (p < 0.01)., Conclusions: Intestinal parasitic pathogens are more common in HIV infected antiretroviral therapy naïve patients. Early detection of enteric pathogens by routine examination of stool samples will help in the management and to improve the quality of life for HIV infected individuals.

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/μL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥ 70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART.

Background & Objective: Enteric parasites are major cause of diarrhoea in HIV infected individuals. The present study was undertaken to detect enteric parasites in HIV infected patients with diarrhoea at different levels of immunity., Methods: The study was carried out at National AIDS Research Institute, Pune, India, between March 2002 and March 2007 among consecutively enrolled 137 HIV infected patients presenting with diarrhoea. Stool samples were collected and examined for enteric parasites by microscopy and special staining methods. CD4 cell counts were estimated using the FACS count system., Results: Intestinal parasitic pathogens were detected in 35 per cent patients, and the major pathogens included Cryptosporidium parvum (12%) the most common followed by Isospora belli (8%), Entamoeba histolytica/Enatmoeba dispar (7%), Microsporidia (1%) and Cyclospora (0.7%). In HIV infected patients with CD4 count < 200 cells/microl, C. parvum was the most commonly observed (54%) pathogen. Proportion of opportunistic pathogens in patients with CD4 count <200 cells/microl was significantly higher as compared with other two groups of patients with CD4 count >200-499 and >or= 500 cells/microl (P=0.001, P=0.016) respectively., Interpretation & Conclusion: Parasitic infections were detected in 35 per cent HIV infected patients and low CD4 count was significantly associated with opportunistic infection. Detection of aetiologic pathogens might help clinicians decide appropriate management strategies.

The longitudinal heterologous neutralization response against two HIV-1 subtype C isolates was studied in 33 ART-naive individuals recently infected with HIV-1 subtype C from India. Seven of 33 (21%) seroconverters demonstrated a consistent response against both isolates (65-100% neutralization), whereas the remaining 26 (79%) were nonresponders. Four of the seven responders demonstrated a neutralization response (>75% neutralization) within 2-3 months of infection and in the remaining three, the response was demonstrated between 22 and 38 months after infection. In the past, HIV vaccines targeted the V3 region for the development of neutralizing antibodies. However, recent studies have shown that anti-V3 antibodies are generated after HIV-1 infection, but are not effective in neutralizing virus. In this study, the V3 sequences of HIV-1 from seven responders were analyzed and compared with those from nonresponders. The V3 region sequences from early and late responders did show certain mutations that were not found in the nonresponders; however none of these mutations could explain the neutralization responses. This suggested that HIV-1 envelope regions other than the V3 domain may be involved in generating a neutralization response. This is the first report that describes the pattern of emergence and persistence of the heterologous neutralization response in recently HIV-1 subtype C-infected individuals from India and studies its association with sequence variation in the V3 region.

Objective: We assessed the extent of anxiety/depression/distress using Hospital Anxiety and Depression Scale (HADS) among a cross-section of HIV test-seekers at a Voluntary Counseling and Testing (VCT) facility in Pune, India., Methods: HADS has 14 items for uniscale with 7 items each for anxiety and depression rated on a four-point Likert scale. Between September 2002 and March 2003, HADS was administered to 150 consecutive HIV tests-seekers attending NARI-Talera VCT facility. Subsequently, HIV testing was done after obtaining informed consent., Results: HADS showed strong internal consistency (Cronbach-alpha 0.77). The prevalence of risk behavior (73.3%) and HIV (45.5%) were high. Education levels influenced anxiety (p = 0.033; 0.008), more so in women (p = 0.044). Repeat test-seekers exhibited significant depression (AOR: 2.9; 95% CI: 1.4-6.1; p = 0.004) and distress (AOR: 2.5; 95% CI: 1.2-5.3; p = 0.017). Marital status influenced the uniscale scores. The HIV positive repeat test-seekers were more anxious (p = 0.035) and depressed (0.037)., Conclusions: Existence of emotional distress among HIV test-seekers, particularly among repeat test-seekers, possibly 'AIDS-anxious' individuals indicates additional counseling needs specifically by introducing gender and education sensitive interventions. VCT staff can be trained to assess emotional distress among HIV test-seekers to formulate long-term intervention.

Background & Objective: Several instruments have been developed specifically to assess the quality of life (QOL) in HIV infected individuals. No information is available in this aspect from India. The present study was thus carried out to assess the QOL among HIV infected persons, to study their relationship with socio-demographic characteristics and stages of disease progression, and to examine change in QOL over time., Methods: One time assessment of QOL on 100 and repeat evaluation on 20 HIV infected persons enrolled in an ongoing longitudinal prospective study of clinical progression was done. Medical Outcome Study (MOS-QOL) core instrument was modified to suit the Indian cultural settings and interview-administered., Results: The overall scale had Cronbach alpha 0.75. Instrument showed significant positive inter-domain correlations and linear association between QOL scores and CD4 counts. QOL was markedly affected in the domains of physical health, work and earnings, routine activities, and appetite and food intake. Women had significantly lower QOL scores despite having less advanced disease. The QOL scores decreased with drop in CD4 counts mainly in the physical health domains. Generally, the QOL scores were high in the follow up visit compared to baseline., Interpretation & Conclusion: The modified MOS scale with Cronbach alpha of more than 0.7 and linear relationship between CD4 counts and the QOL scores indicated that the instrument was reliable and valid for evaluation of QOL in HIV infected persons in India. Comparative lower scores in the domains of physical health indicate medical intervention to greatly benefit the HIV infected persons. Longitudinal studies need to be undertaken to assess the impact of introduction of anti retroviral therapy (ART) through the national programme on disease progression and changes in QOL.

Objective: To study dimensions of Quality of Life (QOL) amongst HIV infected persons, their relationship with socio-demographic characteristics and disease progression., Design: Cross-sectional study with one time assessment of QOL., Methods: Modified Medical Outcome Study (MOS) core instrument [The Medical Outcome Study 116 core set of Measures of functioning and well being, Appendix A, core survey instrument (internet)] was interview--administered to 100 HIV infected individuals., Results: The instrument showed significant positive inter-domain correlations and desired linear association between QOL scores and the CD4 counts. The scale had a Cronbach alpha value of 0.75. QOL was markedly affected in the domains of physical health, work and earnings, routine activities and appetite and food intake. Women had significantly lower QOL scores than men despite having less advanced disease. The QOL scores were significantly lower among persons with lower CD4 counts mainly in different domains of physical health., Conclusions: The modified MOS scale had the desired reliability and validity for evaluation of QOL in the HIV-infected persons in India. Low scores in the domains of physical health compared to other domains suggest a strategy to focus on medical intervention. A need for psychosocial intervention for women was perceived. Longitudinal studies must be done to assess the impact of anti-retroviral therapy being rolled out through the national programme on QOL.

Successful conduct of HIV vaccine trials in a population of great cultural diversity like India could be a challenge. Concerns, knowledge gaps and willingness to participate in future HIV vaccine trials were studied among 349 patients attending three sexually transmitted infections clinics and one reproductive tract infections clinic. Overall willingness to volunteer for HIV vaccine trials was 48%. Women and men at risk of HIV infection were willing to participate in the HIV vaccine trials. Factors associated with increased willingness to participate in these trials were awareness of current HIV vaccine efforts, realization of importance of vaccine for self, concern about adverse events and altruism.