The cost of safe sex: estimating the price premium for unprotected sex during the Avahan HIV prevention programme in India.

There is some evidence that female sex workers (FSWs) receive greater earnings for providing unprotected sex. In 2003, the landscape of the fight against HIV/AIDS dramatically changed in India with the introduction of Avahan, the largest HIV prevention programme implemented globally. Using a unique, cross-sectional bio-behavioural dataset from 3591 FSWs located in the four Indian states where Avahan was implemented, we estimate the economic loss faced by FSWs who always use condoms. We estimate the causal effect of condom use on the price charged during the last paid sexual intercourse using the random targeting of Avahan as an instrumental variable. Results indicate that FSWs who always use condoms face an income loss of 65% (INR125, US$2.60) per sex act compared to peers providing unprotected sex, consistent with our expectations. The main finding confirms that clients have a preference for unprotected sex and that policies aiming at changing clients' preferences and at improving the bargaining power of FSWs are required to limit the spread of HIV.

HIV/AIDS in India: an overview of the Indian epidemic.

The first cases of HIV infection in India were detected in 1986 among female sex workers in Chennai. A rapid increase followed in many states. The current national prevalence is about 0.26% compared with a global average of 0.2%, but the figure in most high-risk groups including female sex workers is much higher (up to 7%). New HIV infections reached a peak in 1998 and have since declined by 60%, although the total number of HIV-positive persons remains stable at 2.1 million, largely probably due to the increased life expectancy following antiretroviral therapy. The Indian epidemic is characterized by low levels in the general population and elevated concentrations among high-risk groups. Transmission is mainly heterosexually driven, with differential burdens across the states. The four main drivers of HIV infection in India differ in order from those elsewhere in the world and are commercial sex work, general heterosexual intercourse, injecting drug use and unprotected anal sex between men who have sex with men. There are distinct differences from state to state in the prevalence of HIV, with some around the national norm of 0.21% but others with over 1% infected. India has embarked on a targeted HIV prevention strategy in recent years which is strongly associated with a fall in infection rate in both low- and high-risk groups.

HIV-infected CD4+ T Cells Use T-bet-dependent Pathway for Production of IL-10 Upon Antigen Recognition.

Interleukin (IL)-10 has been implicated in persistence of pathogens in a number of chronic infections. Infected CD4+ cells upon reactivation with HIV antigens were also shown to produce IL-10, which might contribute to their persistence. Hence, it is crucial to determine mechanisms regulating IL-10 production after activation with HIV antigens for devising effective blocking strategies. In this study, ERK-, T-bet- and FoxP3-dependent pathways were evaluated for their possible roles in IL-10 production by infected CD4+ cells after reactivation with HIV Env. Intracellular and secreted IL-10 levels were determined by flow cytometry and Bioplex assay after treating PBMCs with PD98059, tipifarnib and cyclosporin A for blocking of ERK-, T-bet-and FoxP3-dependent pathways, respectively. Baseline levels of T-bet, pERK were higher in P24+ CD4+ cells as compared to uninfected CD4+ cells, which increased further after activation with Env. Inhibition of T-bet resulted in 2.3-fold reduction of IL-10 expression whereas ERK and FoxP3 inhibition failed to cause suppression of IL-10 expression. Conversely, IL-10 secreted by PBMCs was inhibited maximally after ERK inhibition suggesting its role in regulation of cytokine secretory pathway. IFN-γ was found to be suppressed after treatment with inhibitors of all these pathways. Thus, the study highlighted need for IL-10 blockade along with the use of antigens for therapeutic vaccinations or latency reversal and identified the T-bet-dependent pathway as an important pathway regulating IL-10 production by infected CD4+ cells. However, simultaneous blockade of IFN-γ precludes use of inhibitor of this pathway as an IL-10 blocking strategy.

Sudarshan Kriya yoga improves quality of life in healthy people living with HIV (PLHIV): results from an open label randomized clinical trial.

BACKGROUND & OBJECTIVES: Improving quality of life (QOL) of healthy people living with HIV (PLHIV) is critical needing home-based, long-term strategy. Sudarshan Kriya yoga (SKY) intervention is acknowledged for its positive impact on health. It is hypothesised that SKY would improve PLHIV's QOL, justifying an evaluation. METHODS: In this open label randomized controlled pilot trial, 61 adult PLHIV with CD4 count more than 400 cells/µl and Karnofsky scale score above 70 were enrolled. Those with cardiac disease, jaundice, tuberculosis, or on antiretroviral therapy/yoga intervention were excluded. All were given standard care, randomized to SKY intervention (31: I-SKY) and only standard of care in control (30: O-SOC) arms. The I-SKY participants were trained for six days to prepare for daily practice of SKY at home for 30 min. A validated 31-item WHOQOL-HIVBREF questionnaire was used to document effect in both arms from baseline to three visits at 4 wk interval. RESULTS: Baseline QOL scores, hypertension and CD4 count were similar in both arms. An overall 6 per cent improvement of QOL scores was observed in I-SKY group as compared to O-SOC group, after controlling for baseline variables like age, gender, education and occupation ( p =0.016); 12 per cent for physical ( p =0.004), 11 per cent psychological (p =0.023) and 9 per cent level of independence (p =0.001) domains. Improvement in I-SKY observed at post-training and in the SKY adherence group showed increase in these two domains. CONCLUSIONS: A significant improvement in QOL scores was observed for the three health related QOL domains in SKY intervention arm. This low cost strategy improved physical and psychological state of PLHIV calling for upscaling with effective monitoring for sustainability of quality of life.

Undiagnosed HIV among people who inject drugs in Manipur, India.

Manipur is a geographically isolated state of India characterised by a high HIV prevalence among people who inject drugs (PWID). A low-to-moderate lifetime rate of HIV testing has been documented amongst PWID in Manipur. Little is known about the extent of undiagnosed HIV in this setting and whether uptake of HIV testing (and knowledge of a positive diagnosis) leads HIV-positive PWID to change their risk behaviours. The cross-sectional data (n = 821) analysed for this paper were collected in 2009 for the Integrated Behavioural and Biological Assessment (IBBA) using interviewer-administered questionnaires and the collection of de-linked blood and urine samples. Almost one-third (30.7%) of the participants tested HIV positive. The majority knew where to obtain a confidential HIV test (80.7%), however, half of the HIV-positive participants had either never had an HIV test (37.7%), or had undertaken a test without collecting the result (12.7%). Almost one-quarter (23.4%) of the HIV-positive participants and 17.4% of the HIV-negative participants had shared a needle/syringe with at least one other injector during the preceding month. Encouragingly, HIV-positive participants were significantly more likely than HIV-negative participants to use condoms with their regular sexual partners, however, there was still a high proportion of HIV-positive participants who did not use a condom at last sex with their regular (47.2%) or casual (48.0%) partners. Having taken an HIV test and collected the result was associated with a reduction in HIV-risk behaviours among HIV-positive participants, but not among HIV-negative participants. In conclusion, we found that a substantial proportion of the HIV-positive PWID in Manipur were not aware of their positive status, and risky injecting and sexual practices were commonplace. However, HIV-positive PWID appear to reduce their high-risk behaviours when they become aware of their HIV status highlighting the importance of taking HIV testing coverage to scale.

Differential modulation of phenotypic composition of HIV-infected and -uninfected PBMCs during cryopreservation.

This article was designed to determine variations in phenotypic composition of fresh and frozen PBMCs for assessing utility of cryopreserved PBMCs for phenotypic assays. Relative percentages of effector memory cells increased significantly as against percentages of naïve cells which showed significant decrease after cryopreservation in HIV-uninfected samples. These differences were not significant in HIV-infected individuals. There was no significant difference in the expression of activation markers in fresh and frozen PBMCs except the HLA DR expression on CD8 cells in HIV-infected individuals, which was significantly decreased in frozen PBMCs. Thus, cryopreservation resulted in differential effect on phenotypic composition of PBMCs in HIV-infected and -uninfected individuals.

Syphilis infection among female sex workers in Nagaland, Northeast India: analysing their vulnerability to the infection.

This paper describes the sex work characteristics and factors associated with syphilis among female sex workers (FSWs) in Dimapur district of high HIV prevalence Indian state, Nagaland. The study recruited 426 FSWs in 2006 using respondent-driven sampling. The prevalence of syphilis was 21.1% and HIV prevalence was 11.7%. Approximately half were under 25 years of age. Clients were solicited mainly in public places (32.7%), while hotels/lodges/rented rooms were the most common places of entertainment (57.2%). Condom use during the last sex was 36.5% with occasional and 27% with regular clients. Being married, being widowed/divorced/separated, being illiterate or having a history of drug use increased the likelihood of syphilis infection. Entertaining clients in bars/booze joints decreased the probability of syphilis. FSWs who moved between soliciting in public places or bars/booze joints and then entertaining in hotels/lodges/rented rooms had a higher vulnerability to syphilis. In summary, we found that the vulnerability to syphilis among mostly young FSWs in Dimapur varied according to their sex work characteristics, marital and educational status and drug use habits. They may be more vulnerable to HIV and sexually transmitted infections (HIV/STIs) due to the low rate of condom use. The findings have direct implications for HIV/STI prevention programmes in Northeast India.

Assessment of the scale, coverage and outcomes of the Avahan HIV prevention program for female sex workers in Tamil Nadu, India: is there evidence of an effect?

BACKGROUND: Avahan, the India AIDS Initiative, a large-scale HIV prevention program, using peer-mediated approaches and STI services, was implemented for high-risk groups for HIV in six states in India. This paper describes the assessment of the program among female sex workers (FSWs) in the southern state of Tamil Nadu. METHODS: An analytical framework based on the Avahan impact evaluation design was used. Routine program monitoring data, two rounds of cross-sectional biological and behavioural surveys among FSWs in 2006 (Round 1) and 2009 (Round 2) and quality assessments of clinical services for sexually transmitted infections (STIs) were used to assess trends in coverage, condom use and prevalence of STIs, HIV and their association with program exposure. Logistic regression analysis was used to examine trends in intermediate outcomes and their associations with intervention exposure. RESULTS: The Avahan program in Tamil Nadu was scaled up and achieved monthly reported coverage of 79% within four years of implementation. The cross-sectional survey data showed an increasing proportion of FSWs being reached by Avahan, 54% in Round 1 and 86% in Round 2 [AOR=4.7;p=0.001]. Quality assessments of STI clinical services showed consistent improvement in quality scores (3.0 in 2005 to 4.5 in 2008). Condom distribution by the program rose to cover all estimated commercial sex acts. Reported consistent condom use increased between Round 1 and Round 2 with occasional (72% to 93%; AOR=5.5; p=0.001) and regular clients (68% to 89%; AOR=4.3; p=0.001) while reactive syphilis serology declined significantly (9.7% to 2.2% AOR=0.2; p=0.001). HIV prevalence remained stable at 6.1% between rounds. There was a strong association between Avahan exposure and consistent condom use with commercial clients; however no association was seen with declines in STIs. CONCLUSIONS: The Avahan program in Tamil Nadu achieved high coverage of FSWs, resulting in outcomes of improved condom use, declining syphilis and stabilizing HIV prevalence. These expected outcomes following the program logic model and declining HIV prevalence among general population groups suggest potential impact of high risk group interventions on HIV epidemic in Tamil Nadu.

Barriers to ART adherence & follow ups among patients attending ART centres in Maharashtra, India.

BACKGROUND & OBJECTIVES: Adherence to ART is a patient specific issue influenced by a variety of situations that a patient may encounter, especially in resource-limited settings. A study was conducted to understand factors and influencers of adherence to ART and their follow ups among patients attending ART centres in Maharashtra, India. METHODS: Between January and March 2009, barriers to ART adherence among 32 patients at three selected ART centres functioning under national ART roll-out programme in Maharashtra, India, were studied using qualitative methods. Consenting patients were interviewed to assess barriers to ART adherence. Constant comparison method was used to identify grounded codes. RESULTS: Patients reported multiple barriers to ART adherence and follow up as (i) Financial barriers where the contributing factors were unemployment, economic dependency, and debt, (ii) social norm of attending family rituals, and fulfilling social obligations emerged as socio-cultural barriers, (iii) patients' belief, attitude and behaviour towards medication and self-perceived stigma were the reasons for sub-optimal adherence, and (iv) long waiting period, doctor-patient relationship and less time devoted in counselling at the center contributed to missed visits. INTERPRETATION & CONCLUSIONS: Mainstreaming ART can facilitate access and address 'missed doses' due to travel and migration. A 'morning' and 'evening' ART centre/s hours may reduce work absenteeism and help in time management. Proactive 'adherence probing' and probing on internalized stigma might optimize adherence. Adherence probing to prevent transitioning to suboptimal adherence among patients stable on ART is recommended.

Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India.

The HIV-1 gp41 has been identified as an important target for the immune response, for the development of antiviral and vaccine strategies, and for epidemiologic studies. This study describes the HIV-1 env gp41 region mutations, associated with enfuvirtide (ENF) resistance, in proviral DNA from PBMCs in antiretroviral treatment-naive individuals from Pune, India. Twenty-one antiretroviral drug-naive chronically HIV-1-infected individuals were enrolled. The study sequences belonged to subtype C (n = 17), subtype A1 (n = 2), and CRF_AE (n = 2). In subtype B-infected individuals, the various HR1 region substitutions in env gp41 that have been associated with ENF resistance include A30V, L33S/T/V, L34M, G36D/E/S/V, I37T/K/V, V38A/M/E/G, Q39R, Q40H, N42T/D, N43D/K/S, L44M, L45M, R46M, L54M, and Q56K/R as well as N126K and S138A in the HR2 region. The study sequences did not reveal any ENF resistance-associated mutations at env gp41 amino acid positions: 36 to 45. The presence of L54M and Q56K in combination is associated with 5-fold reduced sensitivity to inhibition by ENF. The mutation L54M was seen in seven subtype C and two CRF_AE study sequences. Q56K was observed in a subtype A1 sequence. All the study sequences harbored N42S, a natural polymorphism associated with increased susceptibility to ENF. Of the mutations V38A and N140I, known to provide immunologic gain, the latter was observed in four subtype C sequences. This is the first study from India highlighting the presence of certain mutations in Indian subtype C env gp41, which may play a role in the evolution of subtype-specific variations in the resistance to ENF and associated immune response.

Profile of primary resistance in HIV-1-infected treatment-naive individuals from Western India.

The majority of the HIV drug resistance (HIVDR) testing studies have focused on subtype B virus. The predominance of subtype C in the Indian subcontinent along with greater access to antiretroviral therapy (ART) necessitates studies on HIVDR genotyping. We determined the prevalence of mutations associated with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and nonnucleoside reverse transcriptase inhibitors (NNRTI) from plasma of 40 antiretroviral drug-naive study participants in Indian HIV-1 pol gene sequences. Of these, 36 sequences belonged to subtype C, two to subtype A1, and two were subtype A1C recombinants. The heterosexual route was the most common route of transmission. Drug resistance-associated mutations were observed in 10% (4/40) of the study participants. The resistance mutation observed in the protease gene was V82A, whereas in the RT gene, M41L, D67N, M184V, and A98G were documented. This is the first study reporting major protease mutations by genotyping in ART-naive individuals from western India.

2-(2,6-Dihalo-phenyl)-3-heteroaryl-2-ylmethyl-1, 3-thiazolidin-4-ones: anti-HIV agents.

A diversity of novel 2-aryl-3-heteroaryl-2-ylmethyl-1,3-thiazolidin-4-ones were designed and synthesized by reacting heteroaryl-2-ylmethyl amine with various 2,6-dihalosubstituted benzaldehydes and mercaptoacetic acid. The title compounds were evaluated for human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) inhibitory activity. The results of in vitro assays showed that some of the compounds were effective inhibitors of HIV-1 reverse transcriptase enzyme at micromolar concentrations with less cytotoxicity in both MT-4 cells as well as acutely infected human T-lymphoid CEM cells. Compounds 4h and 4k emerged as moderately more potent with EC(50) are at 0.20 and 0.21 microM as compared to reference parent compound thiazolobenzimidazoles EC(50) 0.35 microM in MT-4 cells.

Antiretroviral drug resistance testing.

While antiretroviral drugs, those approved for clinical use and others under evaluation, attempt in lowering viral load and boost the host immune system, antiretroviral drug resistance acts as a major impediment in the management of human immune deficiency virus type-1 (HIV-1) infection. Antiretroviral drug resistance testing has become an important tool in the therapeutic management protocol of HIV-1 infection. The reliability and clinical utilities of genotypic and phenotypic assays have been demonstrated. Understanding of complexities of interpretation of genotyping assay, along with updating of lists of mutation and algorithms and determination of clinically relevant cut-offs for phenotypic assays are of paramount importance. The assay results are to be interpreted and applied by experienced HIV practitioners, after taking into consideration the clinical profile of the patient. This review sums up the methods of assay currently available for measuring resistance to antiretroviral drugs and outlines the clinical utility and limitations of these assays.

Low HIV-1 incidence among married serodiscordant couples in Pune, India.

Unlike commercial sex workers and patients attending sexually transmitted infection (STI) clinics, married couples are not typically targeted for HIV risk reduction programs in India. Thus, married partners of HIV-infected persons are at particularly high risk for HIV infection. Between September 2002 and November 2004, 457 HIV-1 sero-discordant, married couples were enrolled in a one-year prospective study of HIV transmission in Pune, India. The HIV incidence among uninfected partners was 1.22 per 100 person-years (95% CI 0.45-2.66), which is much lower than what has been previously reported among discordant couples in Africa. This may be due to higher rates of condom use, lower rates of STIs and higher CD4 T lymphocyte counts, among the Indian HIV sero-discordant couples.

Assessing impaired arm use and learned bias after stroke using unimanual and bimanual steering tasks.

Learned nonuse is often seen in stroke survivors with hemiparesis. In these cases, stroke survivors exhibit a bias for using the less impaired arm on daily living tasks despite latent functionality as measured by clinical motor function. We used the TheraDrive system, a low-cost, stroke rehabilitation system using commercial force-feedback steering wheels along with unimanual and bimanual steering tasks, to quantify the motor impairment, arm use bias and the effect of functioning levels on tracking performance. We present the methodology and tracking results that support the use of steering tasks to detect the presence of motor impairment in the contralateral side of the brain injury, the presence of learned nonuse, the relationship between level of functionality (low-to-medium versus high stroke) and these measures and the effect of handedness and side of injury after stroke.

Prevalence of HIV infection in pregnant women in remote rural areas of Maharastra State, India.

In a study of 304 pregnant women, the prevalence of HIV infection in remote rural areas of western India was 0.7% (confidence interval 0.08-2.3%). It is nearly 2(1/2) times higher than the presumed prevalence for this part of the country.

High-risk behaviour in young men attending sexually transmitted disease clinics in Pune, India.

The present study reports sexual risk factors associated with HIV infection among men attending two sexually transmitted disease (STD) clinics in Pune, India and compares these behaviours between young and older men. Between April 1998 and May 2000, 1872 STD patients were screened for HIV infection. Data on demographics, medical history and sexual behaviour were collected at baseline. The overall HIV prevalence was 22.2%. HIV risk was associated with being divorced or widowed, less educated, living away from the family, having multiple sexual partners and initiation of sex at an early age. The risk behaviours in younger men were different to older men. Younger men were more likely to report early age of initiation of sex, having friends, acquaintances or commercial sex workers as their regular partners, having premarital sex and bisexual orientation. Young men were more educated and reported condom use more frequently compared with the older men. Similar high HIV prevalence among younger and older men highlights the need for focused targeted interventions aimed at adolescents and young men and also appropriate interventions for older men to reduce the risk of HIV and STD acquisition.

Modification of medical outcome study (MOS) instrument for quality of life assessment & its validation in HIV infected individuals in India.

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.