Personal, interpersonal and structural challenges to accessing HIV testing, treatment and care services among female sex workers, men who have sex with men and transgenders in Karnataka state, South India.

BACKGROUND: Despite high HIV prevalence rates among most-at-risk groups, utilisation of HIV testing, treatment and care services was relatively low in Karnataka prior to 2008. The authors aimed to understand the barriers to and identify potential solutions for improving HIV service utilisation. METHODS: Focus group discussions were carried out among homogeneous groups of female sex workers, men who have sex with men and transgenders, and programme peer educators in six districts across Karnataka in March and April 2008. RESULTS: 26 focus group discussions were conducted, involving 302 participants. Participants had good knowledge about HIV and HIV voluntary counselling and testing (VCT) services, but awareness of other HIV services was low. The fear of the psychological impact of a positive HIV test result and the perceived repercussions of being seen accessing HIV services were key personal and interpersonal barriers to HIV service utilisation. Previous experiences of discrimination at government healthcare services, coupled with discriminatory attitudes and behaviours by VCT staff, were key structural barriers to VCT service uptake among those who had not been HIV tested. Among those who had used government-managed prevention of parent to child transmission and antiretroviral treatment services, poor physical facilities, long waiting times, lack of available treatment, the need to give bribes to receive care and discriminatory attitudes of healthcare staff presented additional structural barriers. CONCLUSIONS: Embedding some HIV care services within existing programmes for vulnerable populations, as well as improving service quality at government facilities, are suggested to help overcome the multiple barriers to service utilisation. Increasing the uptake of HIV testing, treatment and care services is key to improving the quality and longevity of the lives of HIV-infected individuals

Vulnerability re-assessed: the changing face of sex work in Guntur district, Andhra Pradesh.

We conducted a qualitative study to examine the impact of an HIV prevention programme on female sex workers' lives in Guntur district, Andhra Pradesh. The study found evidence that, in addition to the HIV prevention programme, structural and environmental factors had recently changed the way sex work was being practiced. Recent closure of the brothels and implementation of a late-night street curfew by the police meant sex work had become more hidden, with clients often solicited using mobile phones from home or their work place (e.g., in the fields or factories). Sex work had become safer, with violence by non-regular partners rarely reported. Women understood the risks of unprotected vaginal sex and reported using condoms with their clients. However, clients were more frequently requesting anal sex, possibly due to recent exposure to pornography following increased accessibility to modern technologies such as mobile phones and the Internet. Anal sex with clients was common but women were often unaware of the associated risks and reported unprotected anal sex. HIV positive and/or older women faced severe financial hardship and difficulty soliciting sufficient clients, and reported unprotected vaginal and anal sex to earn enough to survive. Taken together, the findings from this study suggest changing vulnerability to HIV in this setting. It will be important for HIV prevention programmes to be flexible and creative in their approaches if they are to continue to reach this target community effectively

Changes in risk behaviours and prevalence of sexually transmitted infections following HIV preventive interventions among female sex workers in five districts in Karnataka state, south India

OBJECTIVES: To examine the impact of a large-scale HIV prevention programme for female sex workers (FSW) in Karnataka state, south India, on the prevalence of HIV/sexually transmitted infections (STI), condom use and programme coverage. METHODS: Baseline and follow-up integrated biological and behavioural surveys were conducted on random samples of FSW in five districts in Karnataka between 2004 and 2009. RESULTS: 4712 FSW participated in the study (baseline 2312; follow-up 2400), with follow-up surveys conducted 28-37 months after baseline. By follow-up, over 85% of FSW reported contact by a peer educator and having visited a project STI clinic. Compared with baseline, there were reductions in the prevalence of HIV (19.6% vs 16.4%, adjusted odds ratio (AOR) 0.81, 95% CI 0.67 to 0.99, p=0.04); high-titre syphilis (5.9% vs 3.4%, AOR 0.53, 95% CI 0.37 to 0.77, p=0.001); and chlamydia and/or gonorrhoea (8.9% vs 7.0%, AOR 0.72, 95% CI 0.54 to 0.94, p=0.02). Reported condom use at last sex increased significantly for repeat clients (66.1% vs 84.1%, AOR 1.98, 95% CI 1.58 to 2.48, p<0.001) and marginally for occasional clients (82.9% vs 88.0%, AOR 1.22, 95% CI 0.89 to 1.66, p=0.2), but remained stable for regular partners (32%). Compared with street and home-based FSW, brothel-based FSW were at highest risk of HIV and STI, despite high levels of reported condom use. CONCLUSIONS: This large-scale HIV prevention programme for FSW achieved reductions in HIV and STI prevalence, high rates of condom use with clients and high rates of programme coverage. Improved strategies to increase condom use with regular partners and reduce the vulnerability of brothel-based FSW to HIV are required

Declines in risk behaviour and sexually transmitted infection prevalence following a community-led HIV preventive intervention among female sex workers in Mysore, India.

OBJECTIVE: To investigate the impact on sexual behaviour and sexually transmitted infections (STI) of a comprehensive community-led intervention programme for reducing sexual risk among female sex workers (FSW) in Mysore, India. The key programme components were: community mobilization and peer-mediated outreach; increasing access to and utilization of sexual health services; and enhancing the enabling environment to support programme activities. METHODS: Two cross-sectional surveys among random samples of FSW were conducted 30 months apart, in 2004 and 2006. RESULTS: Of over 1000 women who sell sex in Mysore city, 429 participated in the survey at baseline and 425 at follow-up. The median age was 30 years, median duration in sex work 4 years, and the majority were street based (88%). Striking increases in condom use were seen between baseline and follow-up surveys: condom use at last sex with occasional clients was 65% versus 90%, P < 0001; with repeat clients 53% versus 66%, P < 0.001; and with regular partners 7% versus 30%, P < 0.001. STI prevalence declined from baseline to follow-up: syphilis 25% versus 12%, P < 0.001; trichomonas infection 33% versus 14%, P < 0.001; chlamydial infection 11% versus 5%, P = 0.001; gonorrhoea 5% versus 2%, P = 0.03. HIV prevalence remained stable (26% versus 24%), and detuned assay testing suggested a decline in recent HIV infections. CONCLUSION: This comprehensive HIV preventive intervention empowering FSW has resulted in striking increases in reported condom use and a concomitant reduction in the prevalence of curable STI. This model should be replicated in similar urban settings across India

Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo

BACKGROUND:Telomerase is a reverse transcriptase that maintains the telomeres of linear chromosomes and preserves genomic integrity. The core components are a catalytic protein subunit, the telomerase reverse transcriptase (TERT), and an RNA subunit, the telomerase RNA (TR). Telomerase is unique in its ability to catalyze processive DNA synthesis, which is facilitated by telomere-specific DNA-binding domains in TERT called anchor sites. A conserved glutamine residue in the TERT N-terminus is important for anchor site interactions in lower eukaryotes. The significance of this residue in higher eukaryotes, however, has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS:To understand the significance of this residue in higher eukaryotes, we performed site-directed mutagenesis on human TERT (hTERT) Q169 to create neutral (Q169A), conservative (Q169N), and non-conservative (Q169D) mutant proteins. We show that these mutations severely compromise telomerase activity in vitro and in vivo. The functional defects are not due to abrogated interactions with hTR or telomeric ssDNA. However, substitution of hTERT Q169 dramatically impaired the ability of telomerase to incorporate nucleotides at the second position of the template. Furthermore, Q169 mutagenesis altered the relative strength of hTERT-telomeric ssDNA interactions, which identifies Q169 as a novel residue in hTERT required for optimal primer binding. Proteolysis experiments indicate that Q169 substitution alters the protease-sensitivity of the hTERT N-terminus, indicating that a conformational change in this region of hTERT is likely critical for catalytic function. CONCLUSIONS/SIGNIFICANCE:We provide the first detailed evidence regarding the biochemical and cellular roles of an evolutionarily-conserved Gln residue in higher eukaryotes. Collectively, our results indicate that Q169 is needed to maintain the hTERT N-terminus in a conformation that is necessary for optimal enzyme-primer interactions and nucleotide incorporation. We show that Q169 is critical for the structure and function of human telomerase, thereby identifying a novel residue in hTERT that may be amenable to therapeutic intervention

Violence against female sex workers in Karnataka state, south India: impact on health, and reductions in violence following an intervention program

<p>Abstract</p> <p>Background</p> <p>Violence against female sex workers (FSWs) can impede HIV prevention efforts and contravenes their human rights. We developed a multi-layered violence intervention targeting policy makers, secondary stakeholders (police, lawyers, media), and primary stakeholders (FSWs), as part of wider HIV prevention programming involving >60,000 FSWs in Karnataka state. This study examined if violence against FSWs is associated with reduced condom use and increased STI/HIV risk, and if addressing violence against FSWs within a large-scale HIV prevention program can reduce levels of violence against them.</p> <p>Methods</p> <p>FSWs were randomly selected to participate in polling booth surveys (PBS 2006-2008; short behavioural questionnaires administered anonymously) and integrated behavioural-biological assessments (IBBAs 2005-2009; administered face-to-face).</p> <p>Results</p> <p>3,852 FSWs participated in the IBBAs and 7,638 FSWs participated in the PBS. Overall, 11.0% of FSWs in the IBBAs and 26.4% of FSWs in the PBS reported being beaten or raped in the past year. FSWs who reported violence in the past year were significantly less likely to report condom use with clients (zero unprotected sex acts in previous month, 55.4% vs. 75.5%, adjusted odds ratio (AOR) 0.4, 95% confidence interval (CI) 0.3 to 0.5, p < 0.001); to have accessed the HIV intervention program (ever contacted by peer educator, 84.9% vs. 89.6%, AOR 0.7, 95% CI 0.4 to 1.0, p = 0.04); or to have ever visited the project sexual health clinic (59.0% vs. 68.1%, AOR 0.7, 95% CI 0.6 to 1.0, p = 0.02); and were significantly more likely to be infected with gonorrhea (5.0% vs. 2.6%, AOR 1.9, 95% CI 1.1 to 3.3, p = 0.02). By the follow-up surveys, significant reductions were seen in the proportions of FSWs reporting violence compared with baseline (IBBA 13.0% vs. 9.0%, AOR 0.7, 95% CI 0.5 to 0.9 p = 0.01; PBS 27.3% vs. 18.9%, crude OR 0.5, 95% CI 0.4 to 0.5, p < 0.001).</p> <p>Conclusions</p> <p>This program demonstrates that a structural approach to addressing violence can be effectively delivered at scale. Addressing violence against FSWs is important for the success of HIV prevention programs, and for protecting their basic human rights.</p

Optimal allocation of resources in female sex worker targeted HIV prevention interventions: model insights from Avahan in South India.

BACKGROUND: The Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention's impact could have been optimised for different budget levels. METHODS: Behavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels. RESULTS: As budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥ 20%) would have reduced impact considerably (>40%). DISCUSSION: Our analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV

ABSTRACT The Nobel Prize in Physiology or Medicine was

studies on chromosome termini (telomeres) and their discovery of telomerase, the enzyme that synthesizes telomeres. Telomerase is a unique cellular reverse transcriptase that contains an integral RNA subunit, the telomerase RNA and a catalytic protein subunit, the telomerase reverse transcriptase (TERT), as well as several species-specific accessory proteins. Telomerase is essential for genome stability and is associated with a broad spectrum of human diseases including various forms of cancer, bone marrow failure and pulmonary fibrosis. A better understanding of telomerase structure and function will shed important insights into how this enzyme contributes to human disease. To this end, a series of high-resolution structural studies have provided critical information on TERT architecture and may ultimately elucidate novel targets for therapeutic intervention. In this review, we discuss the current knowledge of TERT structure and function, revealed through the detailed analysis of TERT from model organisms. To emphasize the physiological importance of telomeres and telomerase, we also present a general discussion of the human diseases associated with telomerase dysfunction

Characterization of Physical and Functional Anchor Site Interactions in Human Telomerase▿

Telomerase is a ribonucleoprotein reverse transcriptase (RT) that processively synthesizes telomeric repeats onto the ends of linear chromosomes to maintain genomic stability. It has been proposed that the N terminus of the telomerase protein subunit, telomerase RT (TERT), contains an anchor site that forms stable interactions with DNA to prevent enzyme-DNA dissociation during translocation and to promote realignment events that accompany each round of telomere synthesis. However, it is not known whether human TERT (hTERT) can directly interact with DNA in the absence of the telomerase RNA subunit. Here we use a novel primer binding assay to establish that hTERT forms stable and specific contacts with telomeric DNA in the absence of the human telomerase RNA component (hTR). We show that hTERT-mediated primer binding can be functionally uncoupled from telomerase-mediated primer extension. Our results demonstrate that the first 350 amino acids of hTERT have a critical role in regulating the strength and specificity of protein-DNA interactions, providing additional evidence that the TERT N terminus contains an anchor site. Furthermore, we establish that the RT domain of hTERT mediates important protein-DNA interactions. Collectively, these data suggest that hTERT contains distinct anchor regions that cooperate to help regulate telomerase-mediated DNA recognition and elongation