Publications by authors named "Vartika Sharma"

20 Publications

  • Page 1 of 1

Regulation of Notch signaling by E3 ubiquitin ligases.

FEBS J 2021 Feb 28. Epub 2021 Feb 28.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.

Notch signaling is an evolutionarily conserved pathway that is widely used for multiple cellular events during development. Activation of the Notch pathway occurs when the ligand from a neighboring cell binds to the Notch receptor and induces cleavage of the intracellular domain of Notch, which further translocates into the nucleus to activate its downstream genes. The involvement of the Notch pathway in diverse biological events is possible due to the complexity in its regulation. In order to maintain tight spatiotemporal regulation, the Notch receptor, as well as its ligand, undergoes a series of physical and biochemical modifications that, in turn, helps in proper maintenance and fine-tuning of the signaling outcome. Ubiquitination is the post-translational addition of a ubiquitin molecule to a substrate protein, and the process is regulated by E3 ubiquitin ligases. The present review describes the involvement of different E3 ubiquitin ligases that play an important role in the regulation and maintenance of proper Notch signaling and how perturbation in ubiquitination results in abnormal Notch signaling leading to a number of human diseases.
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http://dx.doi.org/10.1111/febs.15792DOI Listing
February 2021

Deltex positively regulates Toll signaling in a JNK independent manner in Drosophila.

Genes Cells 2021 Feb 8. Epub 2021 Feb 8.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.

Toll pathway is the center for the function of immune system in both Drosophila and mammals. Toll pathway in Drosophila gets activated upon binding of the ligand Spätzle to the receptor, Toll, triggering a series of proteolytic cascade culminating into the activation of the NF-κB factors Dorsal and/or Dif (Dorsal-related immunity factor). Inappropriate activation of the Toll pathway is often associated with systemic inflammation phenotype in the absence of infection, and thus, it is important to understand the regulation of Toll signaling. Deltex (Dx) is a context-dependent regulator of Notch signaling and has been linked with cell-mediated immunity in the mammalian system lately. However, the unambiguous role of Dx in humoral and cell-mediated immunity is yet to be explored. Our study unravels the novel role of Dx in Toll pathway activation. Gain of function of dx in Drosophila larvae results in increased melanotic mass formation and increased lamellocyte production. Our results also reveal the nuclear accumulation of transcription factors Dorsal and Dif and expression of Toll-associated antimicrobial peptides (AMP) in Dx over-expression background. Further, we also tried to elucidate the role of Dx in JNK-independent Toll activation. Here we present Dx as a novel candidate in the regulation of Toll pathway.
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http://dx.doi.org/10.1111/gtc.12837DOI Listing
February 2021

Signaling cross-talk during development: Context-specific networking of Notch, NF-κB and JNK signaling pathways in Drosophila.

Cell Signal 2021 Jun 30;82:109937. Epub 2021 Jan 30.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi 221 005, India. Electronic address:

Multicellular organisms depend on a handful of core signaling pathways that regulate a variety of cell fate choices. Often these relatively simple signals integrate to form a large and complex signaling network to achieve a distinct developmental fate in a context-specific manner. Various pathway-dependent and independent events control the assembly of signaling complexes. Notch pathway is one such conserved signaling mechanism that integrates with other signaling pathways to exhibit a context-dependent pleiotropic output. To understand how Notch signaling provides a spectrum of distinct outputs, it is important to understand various regulatory switches involved in mediating signaling cross-talk of Notch with other pathways. Here, we review our current understanding as to how Notch signal integrates with JNK and NF-κB signaling pathways in Drosophila to regulate various developmental events such as sensory organ precursor formation, innate immunity, dorsal closure, establishment of planar cell polarity as well as during proliferation and tumor progression. We highlight the importance of conserved signaling molecules during these cross-talks and debate further possibilities of novel switches that may be involved in mediating these cross-talk events.
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http://dx.doi.org/10.1016/j.cellsig.2021.109937DOI Listing
June 2021

Deltex cooperates with TRAF6 to promote apoptosis and cell migration through Eiger-independent JNK activation in Drosophila.

Cell Biol Int 2021 Mar 21;45(3):686-700. Epub 2020 Dec 21.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

JNK signaling is a highly conserved signaling pathway that regulates a broad spectrum of cellular processes including cell proliferation, migration, and apoptosis. In Drosophila, JNK signaling is activated by binding of the tumor necrosis factor (TNF) Eiger to its receptor Wengen, and a conserved signaling cascade operates that culminates into activation of dual phosphatase Puckered thereby triggering apoptosis. The tumor necrosis factor receptor (TNFR) associated factor 6 (TRAF6) is an adaptor protein, which transduces the signal from TNFRs and Toll-like receptor/interleukin-1 receptor superfamily to induce a wide spectrum of cellular responses. TRAF6 also acts as the adaptor protein that mediates Eiger/JNK signaling in Drosophila. In a genetic interaction study, deltex (Dx) was identified as a novel interactor of TRAF6. Dx is well known to regulate Notch signaling in a context-dependent manner. Our data suggest that combinatorial action of Dx and TRAF6 enhances the Dx-induced wing nicking phenotype by inducing caspase-mediated cell death. Co-expression of Dx and TRAF6 also results in enhanced invasive behavior and perturbs the normal morphology of cells. The cooperative action of Dx and TRAF6 is attributed to JNK activation, which also leads to ectopic wingless (Wg) and decapentaplegic (Dpp) expression. Our results also reveal that the endocytic pathway component Rab7 may play a pivotal role in the regulation of Dx-TRAF6-mediated activation of JNK signaling. Here, we present the fact that Dx and TRAF6 together activate JNK signaling in an Eiger-independent mechanism.
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http://dx.doi.org/10.1002/cbin.11521DOI Listing
March 2021

Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis.

Nat Commun 2020 06 16;11(1):3062. Epub 2020 Jun 16.

Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.

Anti-tuberculosis (TB) drugs, while being highly potent in vitro, require prolonged treatment to control Mycobacterium tuberculosis (Mtb) infections in vivo. We report here that mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs readily take up Mtb and allow unabated mycobacterial growth despite having a functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type HATPases. Additionally, the classic pro-inflammatory cytokines IFNγ and TNFα aid mycobacterial growth within MSCs. Mechanistically, evading drugs and inflammatory cytokines by MSC-resident Mtb is dependent on elevated PGE2 signaling, which we verify in vivo analyzing sorted CD45Sca1CD73-MSCs from lungs of infected mice. Moreover, MSCs are observed in and around human tuberculosis granulomas, harboring Mtb bacilli. We therefore propose, targeting the unique immune-privileged niche, provided by MSCs to Mtb, can have a major impact on tuberculosis prevention and cure.
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http://dx.doi.org/10.1038/s41467-020-16877-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297998PMC
June 2020

Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block.

Autophagy 2021 02 20;17(2):476-495. Epub 2020 Feb 20.

Cellular Immunology Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India.

Opportunistic bacterial infections amongst HIV-infected individuals contribute significantly to HIV-associated mortality. The role of HIV-mediated modulation of innate mechanisms like autophagy in promoting opportunistic infections, however, remains obscure. Here we show, HIV reactivation in or infection of macrophages inhibits autophagy and helps the survival of pathogenic and nonpathogenic non-tuberculous mycobacterial strains (NTMs). The HIV-mediated impairment of xenophagy flux facilitated bacterial survival. Activation of autophagy by trehalose could induce xenophagy flux and kill intracellular or NTMs either during single or co-infections. Trehalose, we delineate, activates PIKFYVE leading to TFEB nuclear translocation in MCOLN1-dependent manner to induce autophagy. Remarkably, trehalose significantly reduced HIV-p24 levels in -infected PBMCs or PBMCs from treatment-naive HIV patients and also controlled mycobacterial survival within -infected animals. To conclude, we report leveraging of HIV-mediated perturbed host innate-immunity by opportunistic bacterial pathogens and show an attractive therapeutic strategy for HIV and associated co-morbidities. AIDS: acquired immune deficiency syndrome; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; BafA1: bafilomycin A; CFU: colony forming unit; CTSD: cathepsin D; CD63: CD63 molecule; EGFP: enhanced green fluorescent protein; FRET: Förster resonance energy transfer; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GLUT: glucose transporter; HIV: human immunodeficiency virus; hMDMs: human monocyte derived macrophages; IL2: interleukin 2; LAMP1: lysosomal-associated membrane protein 1; LC3B-II: lipidated microtubule-associated proteins 1A/1B light chain 3B; Mtb: ; MTOR: mechanistic target of rapamycin; mRFP: monomeric red fluorescent protein; M6PR: mannose-6-phosphate receptor; NAC: N- acetyl- L -cysteine; NTM's: non-tuberculous mycobacteria; PBMC: Peripheral Blood Mononuclear cells; PIKFYVE: phosphoinositide kinase; FYVE-Type Zinc Finger; PHA: phytohemagglutinin; PMA: phorbol 12-myristate 13-acetate; PtdIns(3,5)P2: Phosphatidylinositol 3,5-bisphosphate; ; ROS: reactive oxygen species; SQSTM1: sequestosome1; TFEB: transcription factor EB; MCOLN1/TRPML1: mucolipin 1; PIP4P1/TMEM55B: Human trans-membrane Protein 55B; UVRAG: UV Radiation Resistance Associate; VPS35: vacuolar protein sorting associated protein 35; WDR45: WD repeat domain 45; YCAM: Yellow Chameleon.
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http://dx.doi.org/10.1080/15548627.2020.1725374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610453PMC
February 2021

Uncovering Structural and Molecular Dynamics of ESAT-6:β2M Interaction: Asp53 of Human β2-Microglobulin Is Critical for the ESAT-6:β2M Complexation.

J Immunol 2019 10 4;203(7):1918-1929. Epub 2019 Sep 4.

Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics, Uppal, Hyderabad 500039, Telangana, India;

ESAT-6 is a small secreted protein of involved in the ESAT-6 secretion system (ESX-1)-mediated virulence and pathogenesis. The protein interacts with β2M, causing downregulation of MHC class I Ag presentation, which could be one of the mechanisms by which it favors increased survival of the bacilli inside the host. In an earlier study, we have shown that the C-terminal region of ESAT-6 is crucial for its interaction with β2M. However, the interface of β2M involved in interaction with ESAT-6 and detailed physicochemical changes associated with ESAT-6:β2M complexation are not fully defined. In this study, using computational and site-directed mutagenesis studies, we demonstrate the presence of strong noncovalent hydrophobic interactions between ESAT-6 and β2M in addition to the vital hydrogen bonding between the aspartate residue (Asp53) of β2M and methionine (Met93) of ESAT-6. Docking-based high-throughput virtual screening followed by 16-point screening on microscale thermophoresis resulted in the identification of two potent inhibitors (SM09 and SM15) that mask the critical Met93 residue of ESAT-6 that is required for ESAT-6:β2M interaction and could rescue cell surface expression of β2M and HLA in human macrophages as well as MHC class I Ag presentation suppressed by ESAT-6 in peritoneal macrophages isolated from C57BL/6 mice. Both SM09 and SM15 significantly inhibited intracellular survival of in human macrophages. Further, we characterized the physicochemical properties involved in the ESAT-6:β2M complexation, which may help in understanding host-pathogen interactions.
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http://dx.doi.org/10.4049/jimmunol.1700525DOI Listing
October 2019

Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication.

Retrovirology 2019 04 29;16(1):12. Epub 2019 Apr 29.

Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Background: The different interactions between viral proteins and cellular host proteins are required for efficient replication of HIV-1. Various reports implicated host cellular proteins as a key factor that either interact directly with HIV-1 integrase (IN) or get involved in the integration process of virus resulting in the modulation of integration step. Polypyrimidine tract binding protein and associated splicing factor (PSF) has diverse functions inside the cell such as transcriptional regulation, DNA repair, acts as nucleic acids binding protein and regulate replication and infectivity of different viruses.

Results: The protein binding study identified the association of host protein PSF with HIV-1 integrase. The siRNA knockdown (KD) of PSF resulted in increased viral replication in TZM-bl cells, suggesting PSF has negative influence on viral replication. The quantitative PCR of virus infected PSF knockdown TZM-bl cells showed more integrated DNA and viral cDNA as compared to control cells. We did not observe any significant difference between the amount of early reverse transcription products as well as infectivity of virus in the PSF KD and control TZM-bl cells. Molecular docking study supported the argument that PSF hinders the binding of viral DNA with IN.

Conclusion: In an attempt to study the host interacting protein of IN, we have identified a new interacting host protein PSF which is a splicing factor and elucidated its role in integration and viral replication. Experimental as well as in silico analysis inferred that the host protein causes not only change in the integration events but also targets the incoming viral DNA or the integrase-viral DNA complex. The role of PSF was also investigated at early reverse transcript production as well as late stages. The PSF is causing changes in integration events, but it does not over all make any changes in the virus infectivity. MD trajectory analyses provided a strong clue of destabilization of Integrase-viral DNA complex occurred due to PSF interaction with the conserved bases of viral DNA ends that are extremely crucial contact points with integrase and indispensable for integration. Thus our study emphasizes the negative influence of PSF on HIV-1 replication.
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http://dx.doi.org/10.1186/s12977-019-0474-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489298PMC
April 2019

Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases.

Front Cell Dev Biol 2019 19;7:38. Epub 2019 Mar 19.

Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Autophagy is an intracellular degradation pathway for malfunctioning aggregation-prone proteins, damaged organelles, unwanted macromolecules and invading pathogens. This process is essential for maintaining cellular and tissue homeostasis that contribute to organismal survival. Autophagy dysfunction has been implicated in the pathogenesis of diverse human diseases, and therefore, therapeutic exploitation of autophagy is of potential biomedical relevance. A number of chemical screening approaches have been established for the drug discovery of autophagy modulators based on the perturbations of autophagy reporters or the clearance of autophagy substrates. These readouts can be detected by fluorescence and high-content microscopy, flow cytometry, microplate reader and immunoblotting, and the assays have evolved to enable high-throughput screening and measurement of autophagic flux. Several pharmacological modulators of autophagy have been identified that act either via the classical mechanistic target of rapamycin (mTOR) pathway or independently of mTOR. Many of these autophagy modulators have been demonstrated to exert beneficial effects in transgenic models of neurodegenerative disorders, cancer, infectious diseases, liver diseases, myopathies as well as in lifespan extension. This review describes the commonly used chemical screening approaches in mammalian cells and the key autophagy modulators identified through these methods, and highlights the therapeutic benefits of these compounds in specific disease contexts.
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http://dx.doi.org/10.3389/fcell.2019.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436197PMC
March 2019

Prevalence and determinants of unprotected sex in intimate partnerships of men who inject drugs: findings from a prospective intervention study.

Int J STD AIDS 2019 03 12;30(4):386-395. Epub 2018 Dec 12.

1 Department of Obstetrics and Gynaecology, International Centre for Reproductive Health, Ghent University, Ghent, Belgium.

Unprotected sex, common among people who inject drugs, puts them and their partners at risk of sexually transmitted infections including human immunodeficiency virus (HIV). This analysis assesses the changes in sexual risk behavior with regular female partners (RFPs), among married men who inject drugs, before and after implementation of a HIV prevention intervention, and identifies correlates of unprotected sex. People who inject drugs (PWID) were assessed at three points: baseline, preintervention follow-up visit (FV)1, and postintervention FV2. Descriptive analysis was used for reporting changes in sexual behavior over time. Generalized estimating equation assessed the population-averaged change in self-reported unprotected sex with an RFP, attributable to intervention uptake. Multivariable logistic regression determined correlates of self-reported unprotected sex with an RFP at FV2. Findings suggest that the proportion of men reporting any unprotected sex remained high (baseline = 46.0%, FV1 = 43.5%, FV2 = 37.0%). A reduction was observed in unprotected sex after the intervention phase, but this could not be attributed to uptake of the intervention. Higher odds of self-reported unprotected sex with an RFP in the past three months at FV2 were associated with self-reported unprotected sex at baseline, living with family, and being HIV-negative. Married male PWID should receive counseling for safe sex with RFPs, especially those who are HIV-negative and live with their families.
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http://dx.doi.org/10.1177/0956462418802142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446434PMC
March 2019

Selective Autophagy and Xenophagy in Infection and Disease.

Front Cell Dev Biol 2018 13;6:147. Epub 2018 Nov 13.

Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Autophagy, a cellular homeostatic process, which ensures cellular survival under various stress conditions, has catapulted to the forefront of innate defense mechanisms during intracellular infections. The ability of autophagy to tag and target intracellular pathogens toward lysosomal degradation is central to this key defense function. However, studies involving the role and regulation of autophagy during intracellular infections largely tend to ignore the housekeeping function of autophagy. A growing number of evidences now suggest that the housekeeping function of autophagy, rather than the direct pathogen degradation function, may play a decisive role to determine the outcome of infection and immunological balance. We discuss herein the studies that establish the homeostatic and anti-inflammatory function of autophagy, as well as role of bacterial effectors in modulating and coopting these functions. Given that the core autophagy machinery remains largely the same across diverse cargos, how selectivity plays out during intracellular infection remains intriguing. We explore here, the contrasting role of autophagy adaptors being both selective as well as pleotropic in functions and discuss whether E3 ligases could bring in the specificity to cargo selectivity.
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http://dx.doi.org/10.3389/fcell.2018.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243101PMC
November 2018

Deltex interacts with Eiger and consequently influences the cell death in Drosophila melanogaster.

Cell Signal 2018 Sep 15;49:17-29. Epub 2018 May 15.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address:

TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila, initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger. Dx is found to act as a novel modulator of JNK-mediated cell death inducing activity of Eiger. Additionally, we observe that dx genetically interacts with eiger during wing development, and these two proteins, Dx and Eiger, colocalize in the cytoplasm. Our analysis reveals that Dx is involved in the cytoplasmic relocalization of Eiger from the cell membrane, thereby influencing Eiger-mediated JNK-activation process. Moreover, we demonstrate that Dx potentiates the activity of Eiger to downregulate Notch signaling pathway by retaining the Notch protein in the cytoplasm. Together, our findings reveal a novel role of Dx to modulate the signaling activity of Eiger and subsequent JNK-mediated cell death.
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http://dx.doi.org/10.1016/j.cellsig.2018.05.003DOI Listing
September 2018

Women and substance use: a qualitative study on sexual and reproductive health of women who use drugs in Delhi, India.

BMJ Open 2017 Nov 19;7(11):e018530. Epub 2017 Nov 19.

International Centre for Reproductive Health, Ghent University, Belgium (former Population Council), Ghent, Oost-Vlaanderen, Belgium.

Objectives: To explore contextual factors that increase vulnerabilities to negative sexual and reproductive health (SRH) outcomes and possible differences in SRH-related behaviours and the needs of women who use drugs (WUD) through non-injecting and injecting routes.

Design: Qualitative study design using semi-structured in-depth interviews.

Participants: Twenty women who injected drugs in the past 3 months and 28 women who reported using drugs through non-injecting routes in the past 1 month.

Setting: Interviews were conducted at community-based, drop-in centres in Delhi, India.

Results: Study findings illustrate that WUD were sexually active and had multiple sex partners including clients of sex work. Transient relationships were reported and many participants engaged in unsafe sex. Factors which affected safe sex behaviours included: gender power imbalance, limited agency for decision-making, lack of accurate information for correct self-risk assessment, and being under the influence of drugs. Despite high awareness, low and inconsistent contraceptive use was reported. Some participants were coerced to conceive while a few others reported their inability to conceive. Violence was a key determinant for SRH outcomes. Perception of certain adverse health outcomes (such as infertility) to be 'common and expected among WUD' influenced access to healthcare. Further, healthcare providers' stigmatising attitudes and lack of women-centric services deterred women from uptake of healthcare services.

Conclusion: Findings highlight that SRH-related behaviours and needs of this group are a complex interplay of multiple determinants which need to be addressed at all levels: individual, family, community and institutional. It is imperative to roll out a 'one-stop-shop' for a comprehensive package of health services. Expansion of existing drop-in-centres could be considered for setting-up community-based women-centric services with appropriate linkage to drug dependence treatment and reproductive health services.
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http://dx.doi.org/10.1136/bmjopen-2017-018530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701983PMC
November 2017

Service utilization and cost of implementing a comprehensive HIV prevention and care program among people who inject drugs in Delhi, India.

Harm Reduct J 2017 06 14;14(1):38. Epub 2017 Jun 14.

Population Council, India Habitat Center, New Delhi, 110003, India.

Background: WHO, UNODC, and UNAIDS recommend a comprehensive package for prevention, treatment, and care of HIV among people who inject drugs (PWID). We describe the uptake of services and the cost of implementing a comprehensive package for HIV prevention, treatment, and care services in Delhi, India.

Methods: A cohort of 3774 PWID were enrolled for a prospective HIV incidence study and provided the comprehensive package: HIV and hepatitis testing and counseling, hepatitis B (HB) vaccination, syndromic management of sexually transmitted infections, clean needles-syringes, condoms, abscess care, and education. Supplementary services comprising tea and snacks, bathing facilities, and medical consultations were also provided. PWID were referred to government services for antiretroviral therapy (ART), TB care, opioid substitution therapy, and drug dependence treatment/rehabilitation.

Results: The project spent USD 1,067,629.88 over 36 months of project implementation: 1.7% on capital costs, 3.9% on participant recruitment, 26.7% for project management, 49.9% on provision of services, and 17.8% on supplementary services. Provision of HIV prevention and care services cost the project USD 140.41/PWID/year. 95.3% PWID were tested for HIV. Of the HIV-positive clients, only 17.8% registered for ART services after repeated follow-up. Reasons for not seeking ART services included not feeling sick, need for multiple visits to the clinic, and long waiting times. 61.8% of the PWID underwent HB testing. Of the 2106 PWID eligible for HB vaccination, 81% initiated the vaccination schedule, but only 29% completed all three doses, despite intensive follow-up by outreach workers. PWID took an average of 8 clean needles-syringes/PWID/year over the project duration, with a mid-project high of 16 needles-syringes/PWID/year. PWID continued to also procure needles from other sources, such as chemists. One hundred five PWID were referred to OST services and 267 for rehabilitation services.

Conclusions: A comprehensive HIV prevention, treatment, and care package is challenging to implement. Extensive efforts are needed to ensure the uptake of and retention in services for PWID; peer educators and outreach workers are required on a continuous basis. Services need to be tailored to client needs, considering clinic timing and distance from hotspots. Programs may consider provision of ART services at selected drop-in centers to increase uptake.
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http://dx.doi.org/10.1186/s12954-017-0165-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471911PMC
June 2017

HIV, Hepatitis B and C among people who inject drugs: high prevalence of HIV and Hepatitis C RNA positive infections observed in Delhi, India.

BMC Public Health 2015 Jul 30;15:726. Epub 2015 Jul 30.

Population Council, Washington, DC, USA.

Background: India has large PWID (persons who inject drugs) population estimated at 177,000. PWIDs are at high risk for HIV, Hepatitis B (HBV) and Hepatitis C (HCV) infections. We report the prevalence of HIV, HBV and HCV infections and correlates of HIV-HCV co-infection among male PWIDs in Delhi.

Methods: 3748 male PWIDs were recruited for a longitudinal HIV incidence study. Participants were tested for HBV and HCV infections at their first follow-up visit (FV1) using serum HBV-surface antigen, and HCV-antibody tests followed by HCV RNA PCR, respectively. All PWIDs who were HIV-negative at enrollment, were re-tested for HIV at FV1. Multinomial logistic regression was employed to identify predictors of HIV, HCV and HIV-HCV co-infection.

Results: Overall prevalence of HIV, HBV and HCV among 2,292 participants tested at FV1 was 25.9%, 9.7% and 53.7%, respectively. 6.4% of the participants had HIV mono-infection, 34.1% had HCV mono-infection, and 19.6% had HIV-HCV co-infection. 26% of HIV-positive participants without HCV were HBsAg positive. In the regression model, having practiced at least one risky injection in the past month (relative risk ratio (RRR): 1.38; 95% CI: 1.01-1.89) and not knowing his own HIV status (RRR: 1.65, 95% CI: 1.25-2.17) were independent predictors for HIV-HCV co-infection. Longer duration of drug injections was associated with a higher likelihood of HCV mono-infection (2-5 years RRR: 2.13; 6-10 years RRR: 2.74; ≥11 years RRR: 3.14) and HIV-HCV co-infection (2-5 years RRR: 5.14; 6-10 years RRR: 8.53; >11 years RRR: 8.03). Higher frequency of injection days/month was associated with a higher likelihood of HCV mono-infection (≤10 days/month RRR: 1.61; 11-20 days/month RRR: 3.15; 21-30 days/month RRR: 3.47) and HIV-HCV co-infections (≤10 days/month RRR: 2.26; 11-20 days/month RRR: 3.46; 21-30 days/month RRR: 4.83).

Conclusions: We report a high prevalence of HIV, HCV and HIV-HCV co-infection among male PWIDs in Delhi. A tenth of the participants were HBsAg positive. Targeted Intervention programs should make HBV/HCV testing, prevention and care more accessible for PWIDs.
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http://dx.doi.org/10.1186/s12889-015-2003-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520270PMC
July 2015

'Women at risk': the health and social vulnerabilities of the regular female partners of men who inject drugs in Delhi, India.

Cult Health Sex 2015 2;17(5):623-37. Epub 2014 Dec 2.

a Population Council , New Delhi , India.

Needle and syringe sharing is common among people who inject drugs and so is unprotected sex, which consequently puts their sex partners at risk of sexually transmitted infections (STIs) including HIV and other blood-borne infections, like hepatitis. We undertook a nested study with the regular female partners of men who inject drugs participating in a longitudinal HIV incidence study in Delhi, India. In-depth interviews were conducted with female partners of 32 men. The interviews aimed to gather focused and contextual knowledge of determinants of safe sex and reproductive health needs of these women. Information obtained through interviews was triangulated and linked to the baseline behavioural data of their partner (index men who injected drugs). The study findings illustrate that women in monogamous relationships have a low perception of STI- and HIV-related risk. Additionally, lack of awareness about hepatitis B and C is a cause of concern. Findings also suggest impact of male drug use on the fertility of the female partner. It is critical to empower regular female partners to build their self-risk assessment skills and self-efficacy to negotiate condom use. Future work must explore the role of drug abuse among men who inject drugs in predicting fertility and reproductive morbidity among their female partners.
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http://dx.doi.org/10.1080/13691058.2014.979885DOI Listing
February 2016

High HIV incidence in a cohort of male injection drug users in Delhi, India.

Drug Alcohol Depend 2014 Jun 30;139:106-14. Epub 2014 Mar 30.

Population Council, 4301 Connecticut Ave NW, Suite 280, Washington, DC 20008, USA.

Background: India has an estimated 177,000 injection drug users (IDU) with a national HIV prevalence of 7.14%. Reliable estimates of HIV incidence are not available for this population.

Methods: We report HIV incidence in a cohort of male, HIV-negative IDUs recruited through peer-referral, targeted outreach and as walk-in clients in Delhi from May to October, 2011. Fourth-generation Antigen-Antibody tests were used to diagnose new infections and results were confirmed using Western blot tests. HIV incidence based on HIV seroconversion was calculated as number of events/person-years. Cox regression was used to identify significant (p<0.05) seroconversion predictors.

Results: A total of 2790 male HIV-negative IDUs were recruited at baseline; 67.4% (n=1880) returned for their first follow-up visit and 96% (n=1806) underwent HIV testing. Participants were followed for a median of 9.7 months. A total of 112 new HIV infections occurred over a cumulative 1398.5 person-years of follow-up resulting in an incidence rate of 8.01 new infections/100 person-years (95% CI: 6.65-9.64); 74% of these participants reported risky injection practices in the past month. In multivariate analysis, moderate-high risk injection behaviors (Adjusted Hazard Ratio [AHR] 2.59; 95% CI 1.45-4.62) were associated with a higher risk of new infections.

Conclusions: Male IDUs in Delhi continue to practice unsafe injection practices leading to high sero-incidence despite the availability of HIV prevention services offered through targeted intervention programs.
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http://dx.doi.org/10.1016/j.drugalcdep.2014.03.021DOI Listing
June 2014

Strategies for recruiting injection drug users for HIV prevention services in Delhi, India.

Harm Reduct J 2013 Sep 25;10:16. Epub 2013 Sep 25.

Population Council, Zone 5A, Ground Floor, India Habitat Centre, Lodi Road, New Delhi 110003, India.

Background: We utilized multiple recruitment approaches to recruit IDUs in a longitudinal cohort study to examine HIV incidence and behavior change pre- and post-introduction of comprehensive HIV prevention services.

Methods: IDUs were recruited through peer referral, targeted outreach by outreach workers (ORWs) and as walk-in clients at drop-in centers. Participants received monetary compensation for participation (USD 0.80). Participants were given recruitment coupons to recruit peers (regardless of recruitment method). For peer referral, participants received a food coupon, as secondary compensation, for each peer he/she successfully recruited. We report the profile of IDUs by recruitment method, based on the baseline behavioral survey and HIV test results. Cost per IDU recruited by recruitment method was also calculated.

Results: A total of 3,818 IDUs were recruited between May 2011 and October 2011. More than half of the study participants were recruited through targeted outreach (ORW: 53.6%; peer-referral: 26.3%; walk-ins: 20.1%). Of the participants who were given recruitment coupons, 92.7% recruited no peers. Those who successfully recruited at least one peer were significantly more likely to be in a stable living accommodation compared to those who did not recruit any peers (51.1% versus 42.7%; p < 0.05). Only 45.9% of the food coupons were claimed for successful recruitment of peers. Peer-referred IDUs were more likely to be living with family or relatives (50.7% versus ORW: 40.1% and walk-in: 39.8%; p < 0.001) rather than on the street or shared housings compared to the other two recruitment modes. Walk-ins were more likely than peer-referred and ORW-referred IDUs to be HIV-positive (walk-ins: 26.1%; peer-referred: 19.1%; ORW: 19.9%; p < 0.01) and have risky injection practices (walk-ins: 62.2%; ORW: 57.0%; peer-referred: 58.6%; p < 0.05). The cost per IDU recruited through ORW referral method was the most costly at USD 16.30, followed by peer-referral at USD 8.40 and walk-in at USD 7.50.

Conclusion: When recruiting a large number of IDUs, using multiple recruitment modes is ideal with regard to diversification of IDU characteristics and risk profile. Although it was the most costly, ORW recruitment was more effective than the other two methods. Lack of monetary compensation for successful recruitment of peers may have hampered peer-referral.
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http://dx.doi.org/10.1186/1477-7517-10-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849590PMC
September 2013

High uptake of HIV testing in a cohort of male injection drug users in Delhi, India: prevalence and correlates of HIV infection.

AIDS Behav 2013 Sep;17(7):2479-89

Population Council, Zone 5A, India Habitat Centre, New Delhi, 110003, India.

We report baseline findings from a longitudinal cohort study to examine HIV incidence, high-risk injection and sexual behaviors of 3,792 male injection drug users (IDUs) in Delhi. The majority (95.4 %) accepted HIV testing; HIV prevalence was 21.9 %. In multivariate analysis, belonging to states adjacent to Delhi (AOR: 1.23; 95 % CI: 1.07-1.52), earning INR 500-1,500 (AOR: 2.38; 95 % CI: 1.43-3.96); duration of drug use 2-5 years (AOR: 2.02; 95 % CI: 1.09-3.73), 6-10 years (AOR: 2.81; 95 % CI: 1.55-5.11), ≥11 years (AOR: 3.35; 95 % CI: 1.84-6.11); prior HIV testing (AOR: 1.60; 95 % CI: 1.35-1.91), self-reported risky-injection behavior (AOR: 1.60; 95 % CI: 1.33-1.92), and utilization of harm-reduction services (AOR: 1.32; 95 % CI: 1.11-1.58) were positively associated with HIV infection. Alcohol use ≤2 times/week (AOR: 0.67; 95 % CI: 0.55-0.82) or ≥3 times/week (AOR: 0.74; 95 % CI: 0.54-1.01), unit increase in age (AOR: 0.99; 95 % CI: 0.98-1.00), ≥7 years of schooling (AOR: 0.82; 95 % CI: 0.66-1.02) and unsafe sex with any female partner (AOR: 0.69; 95 % CI: 0.55-0.86) were negatively associated with HIV infection. HIV prevalence remains high among male IDUs in Delhi. HIV prevention programs should include comprehensive package of services for IDUs.
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http://dx.doi.org/10.1007/s10461-013-0442-zDOI Listing
September 2013

Will adoption of the 2010 WHO ART guidelines for HIV-infected TB patients increase the demand for ART services in India?

PLoS One 2011 8;6(9):e24297. Epub 2011 Sep 8.

Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, New Delhi, India.

Background: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm(3) or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients.

Methods: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records.

Results: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen.

Conclusion: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169570PMC
January 2012