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.

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.

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.

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.

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.

Comparing modified and plain peptide linked enzyme immunosorbent assay (ELISA) for detection of human immunodeficiency virus type-1 (HIV-1) and type-2 (HIV-2) antibodies.

Serological diagnosis of human immunodeficiency virus (HIV) based on detection of HIV antibodies is one of the easiest, cheapest and simplest assay. Synthetic peptides corresponding to immunodominant regions of envelope glycoprotein (gp41, V3 loop for HIV-1 and gp36 for HIV-2) were used in the present study, to detect the anti-HIV antibodies in sera of Sexually Transmitted Diseases (STD), Tuberculosis (TB), Anti-Natal Care (ANC) patients. About 550 serum samples were tested using Enzyme Linked Immunosorbent Assay (ELISA) technique. The human sera positive for antibody to HIV-1 and HIV-2, reacted to different degrees with these peptides when used as a plain peptide with or without CGG motif/biotin motif at the amino terminus. The selected sequences are of Indian strain with 'C' serotype. The results showed a 100% sensitivity and specificity for V3 loop peptide and 98% sensitivity and specificity for gp41 peptide containing CGG moiety while the plain peptides showed similar sensitivities but low specificity's, i.e. 98% for V3 loop peptide and 42% for gp41 peptide when reacted with HIV-1 positive sera. The presence of biotin at the amino terminus did not provide any beneficial effect in increasing the sensitivity although the specificity was enhanced for both the peptide sequences, i.e. gp41 and V3 loop peptide. Furthermore, the gp36 peptide containing CGG moiety detected the HIV-2 sera with 100% sensitivity and 98% specificity while the sensitivity and specificity of gp36 plain peptide was reduced to 98 and 90%. Thus the study overall highlighted the importance of synthetic peptides containing CGG moiety as a capture antigen in detecting both HIV-1 & 2 sera using an indigenously built ELISA system which is simple, cheap, sensitive and cost effective for rural areas.

Sensitivity and specificity of rapid HIV testing of pregnant women in India.

OBJECTIVE: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.

Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested case-control study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow-up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1; p =.01). No such association was observed in case of other non-provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.

Production & characterization of monoclonal antibodies to Mycobacterium tuberculosis.

BACKGROUND & OBJECTIVES: Monoclonal antibodies (MAbs) against Mycobacterium tuberculosis H37Rv culture filtrate (CF) were raised by immunizing BALB/c mice and characterization was done. Attempts have been directed towards identifying mycobacterial antigens in biological fluids by employing polyclonal and monoclonal antibodies specific for M. tuberculosis. Immunohistologic studies, using MAbs for the localization of whole or fragmented bacilli in the biopsy specimens were also carried out. METHODS: Intrasplenic IS and intraperitoneal i.p. routes of immunization, were compared. The MAbs were characterized for their isotype, binding specificity, nature of binding epitope, reactivity in immunoassays etc. RESULTS: IS and i.p. routes of immunization, were compared and i.p. was found superior. Ten MAbs designated TRC 1-10 were produced. Of these, 7 MAbs, TRC 1-7 reacted with the 30/31 kDa doublet (antigen 85 complex), TRC 8 with 12 kDa in addition to 30/31 kDa and TRC 9 and 10 with the 24 and 12 kDa antigens respectively. Six MAbs were classified as broadly cross reactive and 2 showed limited cross reactivity. TRC 8 and 10 showed species specificity. Employing TRC 8 in sandwich ELISA, antigen was detected in sera from 17 of 25 pulmonary tuberculosis patients and 3 of 20 controls. TRC 8 was found to be useful in detecting antigens specifically in M. tuberculosis and M. leprae infected tissues, by immunoperoxidase staining. INTERPRETATION & CONCLUSION: TRC 8 was found to be restricted in its reactivity to M. tuberculosis complex and M. leprae. TRC 8 may prove useful in immuno-diagnosis of tuberculosis.

Relationship between clinical conditions and CD4 counts in HIV-infected persons in Pune, Maharashtra, India.

BACKGROUND: A decade after the detection of human immunodeficiency virus (HIV) infection in India, a steady increase in the number of patients with acquired immunodeficiency syndrome (AIDS) has been observed. The therapeutic options for patients with AIDS in developing countries include chemoprophylaxis and identifying and treating opportunistic infections. CD4 counts help in clinical monitoring and making decisions about initiating antiretroviral therapy or chemoprophylaxis. Flowcytometry is expensive and available only at specialized laboratories. Therefore, the possibility of using clinical indicators to predict low CD4 counts and disease progression needs to be explored. METHODS: This cross-sectional study was conducted among 137 HIV-infected persons investigated at an HIV reference centre in Pune. The study methods comprised pre-test counselling, informed consent, blood withdrawal and clinical evaluation. Serum samples were tested for HIV and CD4 counts were estimated on FACSort. RESULTS: Study participants commonly reported with oral candidiasis, herpes zoster, pulmonary tuberculosis, lymphadenopathy, weight loss, rash, diarrhoea and fever. CD4 counts were significantly lower among men, symptomatic patients and those with oral candidiasis, weight loss and multiple clinical conditions. The sensitivity of most of the clinical conditions was low, the specificity was high and the positive predictive value of oral candidiasis and weight loss for low CD4 counts was > 75%. CONCLUSION: The presence of oral candidiasis and weight loss were highly predictive of low CD4 counts and these can be considered as markers of HIV disease progression. Absence of clinical conditions was found to be a good predictor of high CD4 counts. Larger systematic natural history studies may help in identifying clinical conditions that could have a prognostic significance among HIV-infected people.

Preliminary observations on lymphocyte subpopulations in HIV seropositive & HIV seronegative tuberculosis patients in Pune, India.

CD4 and CD8 lymphocyte counts were determined in 59 HIV seropositive and 41 HIV seronegative newly diagnosed tuberculosis patients in Pune. There were significant differences in the CD4 counts and CD4/CD8 ratios between HIV seropositive and HIV seronegative tuberculosis patients. Majority of the HIV seropositive patients had a CD4 count less than 500 cells/cu.mm, whereas among the HIV seronegative patients, majority had a CD4 count more than 500 cells/cu.mm. In HIV seropositive patients with extrapulmonary and pulmonary tuberculosis, the CD4 counts were lower than in those who had only pulmonary or extrapulmonary tuberculosis. There was no significant differences in the CD8 counts between HIV seropositive and HIV seronegative tuberculosis patients, except for patients with pulmonary cavity, where the CD8 counts were significantly higher in HIV seropositive tuberculosis patients. In HIV seropositive individuals with pulmonary tuberculosis, the CD8 counts in those with pulmonary cavity were higher than in those without any pulmonary cavity. Absence of cavitation and presence of pulmonary with extrapulmonary tuberculosis occurred when immune activation was at a lower level.