Validation of an indigenous assay for rapid molecular detection of rifampicin resistance in presumptive multidrug-resistant pulmonary tuberculosis patients.

BACKGROUND & OBJECTIVES: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. METHODS: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. RESULTS: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. INTERPRETATION & CONCLUSIONS: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

Occurrence of APOBEC3G variations in West Indian HIV patients.

The genetic variations in APOBEC3G gene are correlated with HIV disease progression. These variations differ in different ethnic groups. The prevalence of APOBEC3G (-90C/G, -571G/C) variations have not been studied in Indian population. Hence, we assessed the occurrence of APOBEC3G polymorphisms in HIV patients and its association with acquisition of HIV and disease progression. Polymorphisms in APOBEC3G were genotyped in a total of 153 HIV patients, naïve to ARV and 156 healthy controls by PCR-RFLP method. In single locus model, the frequency of distribution of APOBEC3G -90CG, -571 GC genotypes were higher in HIV patients as compared to healthy controls (57.5% vs. 50.0%, OR = 1.22; 17.0% vs. 12.8%, OR = 1.39). In double locus model, the dominant -571 GC + CC genotype was distributed at a much higher frequency in HIV patients as compared to healthy controls (18.3% vs. 14.1%, OR = 1.50). The frequency of APOBEC3G -571CC and CC + GC genotypes were higher in early HIV disease stage as compared to healthy controls (23.9% vs. 12.8%, OR = 2.23, P = 0.08; 28.3% vs. 14.1%, OR = 2.40, P = 0.04). APOBEC3G-571 GC and GC + CC genotypes were more prevalent in HIV patients consuming tobacco and alcohol as compared to non-users (22.7% vs. 15.3%, OR = 1.71, P = 0.56; 27.3% vs. 16.5%, OR = 1.90, P = 0.39 and 31.6% vs. 13.6%, OR = 2.31, P = 0.08; 36.8% vs14.8%, OR = 2.49, P = 0.04, respectively). In conclusion, APOBEC3G-571G/C polymorphism was associated with the early stage of HIV infection and could potentially influence HIV disease progression in alcohol users. The distribution of APOBEC3G polymorphisms and its haplotypes were not significantly different between HIV patients and healthy controls.

IL-1RN and IL-1ß Polymorphism and ARV-Associated Hepatotoxicity.

The severity of hepatic injury depends upon cytokines. Previous studies associated IL-1RN allele 2 with IL-1ß production. Hence, we examined the association of IL-1 RN and IL-1ß polymorphisms with ARV-associated hepatotoxicity. Genotyping of IL-1RN (VNTR), IL-1ß (-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR = 1.41, P = 0.25; OR = 1.67, P = 0.31). IL-1ß-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR = 3.74, P = 0.05). IL-1ß-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR = 1.80, P = 0.90). IL-1ß-511CT and -511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR = 2.29, P = 0.27; OR = 2.64, P = 0.19). IL-RN 2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR = 1.42, P = 0.64, OR = 8.79, P = 0.09). IL-1ß-511CT and -511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR = 4.29, P = 0.20; OR = 1.95, P = 0.56). IL-1ß-511CT and -511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR = 2.56, P = 0.26; OR = 2.84, P = 0.24). IL-1ß-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation.

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.

Impact and operational feasibility of TrueNat™ MTB/Rif under India's RNTCP.

BACKGROUND: The Revised National Tuberculosis Control Programme (RNTCP) in Andhra Pradesh, India, introduced TrueNat™ MTB/Rif, a rapid molecular test for detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance at 193 TB units (TUs) in October 2018. We evaluated its impact on TB diagnosis and assessed the operational feasibility of its deployment at point-of-care (POC) settings. METHODS: We compared the number of presumptive TB cases tested and the number (proportion) of microbiologically positive before (January-August 2018) and after (January-August 2019) the deployment of TrueNat. We interviewed laboratory technicians and Senior TB Laboratory Supervisor from 25 randomly selected TUs to assess operational feasibility. RESULTS: In 2018, 10.5% (range 8.9-13.1) of 245,989 presumptive cases tested were positive. In 2019, of the 185,435 presumptive cases tested, 13.7% (range 9.6-18.9) were positive. The proportion of presumptive TB cases in whom MTB was detected using TrueNat was 14.4% (range 10.0-21.2). TrueNat significantly increased case detection (incidence rate ratio [IRR] 1.30; 95%CI 1.15-1.46), yielding an additional 18 TB cases per 100 000 population. Laboratory technicians became comfortable in performing TrueNat after a median of 10 tests (interquartile range 5-17.5). Invalid reports declined from 6.8% to 3.6%. CONCLUSION: The deployment of TrueNat as POC diagnostic test improved case detection and was operationally feasible under RNTCP.

Effect of matrix metalloproteinase-21 (572C/T) polymorphism on HIV-associated neurocognitive disorder.

Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV-associated neurocognitive disorders (HAND). The coding region polymorphism in MMP-21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP-21 polymorphism with the modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. Genotyping of MMP-21 572C/T polymorphism was performed by PCR-RFLP in total 150 HIV-infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP-21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP-21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP-21 572TT genotype underrepresented in HIV-infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP-21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP-21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP-21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV-infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP-21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP-21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.

Prevalence of MMP-8 gene polymorphisms in HIV-infected individuals and its association with HIV-associated neurocognitive disorder.

Matrix metalloproteinases (MMPs) are well-known as mediators of neuroinflammation in HIV-associated neurocognitive disorder (HAND). Increased levels of MMP-8 have been observed in the HIV-infected patients. Thus, the aim of this study was to evaluate the association of MMP-8 gene polymorphisms with modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. We enrolled a total of 150 HIV-infected individuals, 50 HAND patients, 100 HIV-infected and 150 healthy individuals. MMP-8 (-799C/T, +17C/G) polymorphisms were genotyped by PCR-RFLP. MMP-8 -799TT genotype and +17G allele showed the higher risk for modulation of HAND severity (OR=2.20, P=0.19; OR=1.97, P=0.23). MMP-8 -799TT genotype differed significantly in HIV-infected individuals compared to healthy controls (20.0% vs. 11.3%, OR=2.36, P=0.048). Haplotype TG increased the risk for modulation of HAND severity (OR=2.29, P=0.29). MMP-8 -799TT and +17CG genotypes were overrepresented in the intermediate HIV disease stage compared with healthy controls (25.9% vs. 11.3%, OR=4.34, P=0.021, 14.8% vs. 9.3%, OR=2.88, P=0.11). MMP-8 +17CG genotype enhanced the risk for modulation of HAND severity in tobacco using HAND patients (OR=5.01, P=0.17). MMP-8 -799TT genotype was more frequent in tobacco using HIV-infected individuals compared with nonusers (26.3% vs. 16.7%, OR=2.08, P=0.32). MMP-8 +17CG genotype increased the risk for modulation of HAND severity in alcohol using HAND patients (OR=4.99, P=0.18). In conclusion, MMP-8 polymorphisms independently and with alcohol and tobacco usage revealed a trend of higher risk for the modulation of HAND severity. MMP-8 -799TT genotype was associated with the advancement of HIV disease.

Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development of HAND and modulation of pathogenesis of HAND.

The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factors such as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms with development of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIVinfected individuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3 were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1- 16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607 1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND.

Rate of hospitalization and inpatient care costs for HIV-1-infected patients in Pune, India.

BACKGROUND: The transition of human immunodeficiency virus (HIV) infection to acquired immune deficiency syndrome (AIDS) has begun in India, and an increase in AIDS-related hospitalizations and deaths is an anticipated challenge. We estimated the rates of hospitalization and inpatient care costs for HIV-1-infected patients. METHODS: Data were analysed on 381 HIV-1-infected persons enrolled in a HIV-1 discordant couples' cohort between September 2002 and March 2004. Inpatient care costs were extracted from select hospitals where the study patients were hospitalized and the average cost per hospitalization was calculated. RESULTS: A majority of the patients were in an advanced state of HIV-1 disease with the median CD4 counts being 207 cells/cmm (range: 4-1131 cells/cmm). In all, 63 participants who did not receive antiretroviral therapy required hospitalization, 53 due to HIV-1-related illnesses and the remaining 10 due to worsening of pre-existing conditions. The overall HIV-1-related hospitalization rate was 34.2 per 100 person-years (95% CI: 26.94-42.93). The median duration of HIV-1-related hospitalization was 10 days (range 2-48 days) and the median cost was Rs 17,464 (range: Rs 400-63,891). CONCLUSION: It is necessary to strengthen the inpatient care infrastructure and supporting diagnostic set-up, and work out economically optimized treatment algorithms for HIV-1-infected patients. Although this analysis does not cover all costs and may not be generalizable, these baseline data might be a useful reference while planning related studies accompanying the government-sponsored programme to roll out antiretroviral therapy to AIDS patients.

HIV testing and counseling among men attending sexually transmitted disease clinics in Pune, India: changes in condom use and sexual behavior over time.

OBJECTIVES: To describe changes in sexual behavior and condom use among male heterosexual clients at two public sexually transmitted disease (STD) clinics in Pune, after exposure to HIV testing, counseling, and condom promotion. DESIGN: From 13 May 1993 to 11 April 1997, 6819 heterosexual men were screened for HIV infection as part of the HIV Network for Prevention Trials study. A total of 1628 HIV-seronegative men agreed to return at 3-month intervals for repeated HIV counseling and testing. Counseling at each visit focused on reinforcing messages of monogamy, condom use with sexual partners, and provision of government-provided condoms. METHODS: Data were collected at baseline and at subsequent 3-month intervals, on demographics, previous STD diagnoses, medical history, sexual behavior, knowledge of HIV/AIDS, and practices related to the prevention of HIV. STD were assessed through physical examination and specimen collection, and blood was drawn for HIV-1 and HIV-2 antibody testing. RESULTS: The level of consistent condom use with sex workers increased proportionately with follow-up time: at 6 months men were 2.8 times more likely to consistently use condoms (P < 0.001), at 18 months they were 3.6 times more likely (P < 0.001), and after 24 months they were 4.7 times more likely to be using condoms every time. The risk of HIV seroconversion in men was lowest for those who reported 'always' using condoms (adjusted relative risk, 0.68; P = 0.42; HIV incidence, 4.0) compared with those who reported 'never' using a condom (adjusted relative risk, 2.94; P < 0.001; HIV incidence, 14.0). CONCLUSION: Ongoing counseling and testing was positively associated with risk-reduction behaviors amongst a large proportion of men recruited for this study.

The influence of alpha-thalassaemia on the haematological & clinical expression of sickle cell disease in western India.

We evaluated the clinical and haematological features of 29 sickle cell anaemia patients with associated alpha-thalassaemia and 22 sickle cell homozygotes with a normal alpha-globin genotype from western India. The presence of alpha-thalassaemia resulted in significantly higher haemoglobin (Hb), haematocrit (HCT), red blood cells counts (RBC) and haemoglobin A2 (HbA2) levels but lower mean cell haemoglobin (MCH) and mean cell volume (MCV). The clinical presentation in these patients was also milder with fewer episodes of painful crisis, chest syndromes, infections, requirement of hospitalization and blood transfusions. However, splenomegaly was more common as compared to the patients with a normal alpha-globin genotype. It is evident from the present study that alpha-thalassaemia could be an important genetic factor modulating the clinical expression and haematological severity of sickle cell anaemia in this region.

Evidence for high prevalence & rapid transmission of HIV among individuals attending STD clinics in Pune, India.

Prevalence and incidence of HIV-1 infection among persons attending two STD clinics in Pune between May 1993 and October 1995 are reported. On screening 5321 persons, the overall prevalence of HIV-1 infection was found to be 21.2 per cent, being higher in females (32.3%) than in males (19.3%). Analysis of behavioural and biological factors showed that old age, sex work, lifetime number of sexual partners, receptive anal sex, lack of circumcision, genital diseases and lack of formal education were related to a higher HIV-1 seroprevalence. The observed incidence rate of 10.2 per cent per year was very high, much higher in women than in men (14.2% and 9.5% per year respectively) and over three times higher among the sex workers. Females in sex work, males having recent contacts with female sex workers (FSWs) and living away from the family and persons with previous or present genital diseases had a higher risk of seroconversion. Condom usage was shown to have a protective effect in seroprevalence and seroincidence analysis. With limited available resources and lack of a suitable vaccine or a drug, long-term prevention policy of creating awareness in the community must be supplemented by strengthening STD control measures and promotion of condom use and safe sex. Factors related to availability and utilization of condoms must be carefully investigated.

Risk factors for HIV infection in people attending clinics for sexually transmitted diseases in India.

OBJECTIVE: To investigate the risk factors for HIV infection in patients attending clinics for sexually transmitted diseases in India. DESIGN: Descriptive study of HIV serology, risk behaviour, and findings on physical examination. SUBJECTS: 2800 patients presenting to outpatient clinics between 13 May 1993 and 15 July 1994. SETTING: Two clinics and the National AIDS Research Institute, in Pune, Maharashtra State, India. MAIN OUTCOME MEASURE: HIV status, presence of sexually transmitted diseases, and sexual behaviour. RESULTS: The overall proportion of patients infected with HIV was 23.4% (655/2800); 34% (184) of the women and 21% (459) of the men were positive for HIV infection. Of the 560 women screened, 338 (60%) had a reported history of sex working, of whom 153 (45%) were infected with HIV-1. The prevalence of HIV-1 infection in the 222 women who were not sex workers was 14%. The significant independent characteristics associated with HIV infection based on a logistic regression analysis included being a female sex worker, sexual contact with a sex worker, lack of formal education, receptive anal sex in the previous three months, lack of condom use in the previous three months, current or previous genital ulcer or genital discharge, and a positive result of a Venereal Disease Research Laboratory test. CONCLUSIONS: In India the prevalence of HIV infection is alarmingly high among female sex workers and men attending clinics for sexually transmitted diseases, particularly in those who had recently had contact with sex workers. A high prevalence of HIV infection was also found in monogamous, married women presenting to the clinics who denied any history of sex working. The HIV epidemic in India is primarily due to heterosexual transmission of HIV-1 and, as in other countries, HIV infection is associated with ulcerative and non-ulcerative sexually transmitted diseases.

PIP: During May 1994-July 1995 in India, health workers at two clinics for sexually transmitted diseases (STDs) in Pune provided HIV serological screening and a physical examination to 2800 patients who completed a questionnaire, so that researchers could identify risk factors for HIV-1 infection in this high-risk population. 60% of the female STD patients were sex workers. 90% of the men had contact with a sex worker within the last 3 months. 14% of all STD patients were women who were not sex workers. 82% of these were married and monogamous. 13% of the married and monogamous women tested positive for HIV-1. Overall, 23.4% of all STD patients tested positive for HIV-1. Only 24% of all STD patients had used condoms during the last 3 months. The leading clinical diagnosis was chancroid (33% for men and 20% for women). The logistic regression analysis showed that the risk factors for HIV-1 infection were: being a sex worker (odds ratio [OR] = 3.7; p 0.001), contact with a sex worker (OR = 1.71; p = 0.01), receptive anal sex (OR = 3.52; p 0.001), tattooed after 1985 (OR = 1.31; p = 0.01), current or previous genital ulcer (OR = 1.29; p = 0.01), and a positive result of a Venereal Disease Research Laboratory test (OR = 1.33; p = 0.01). Protective factors were some formal education (OR = 0.76; p = 0.02), and condom use (sometimes/always, OR = 0.75; p = 0.03). These findings indicate a need for comprehensive and national STD services in India to control STDs and a health education campaign on HIV/AIDS to reduce high risk behavior.

Adolescents living with HIV in India - the clock is ticking.

The term "Adolescence" literally means "to emerge" or "to attain identity" and is essentially the period of rapid physical and psychological development starting from the onset of puberty to complete growth. All adolescents go through a myriad of physical, psychological, neurobehavioural, hormonal and social developmental changes. Given the social taboos often surrounding puberty, the lives of millions of adolescents worldwide are at risk because they do not have the information, skills, health services and support they need to go through the enormous, rapid changes that adolescence brings. A HIV infected adolescent particularly presents enormous challenges in the current cultural and social context of India. The distinct groups of adolescents in the context of HIV are those who were infected at birth and survived and those who became infected during adolescence. Risk factors and situations for adolescents contracting HIV infection are life on streets, lack of adult love/care and support, extreme poverty, child trafficking, migrant population, exploitation in terms of sex and labor. HIV-infected adolescents with long standing HIV infection often face considerable physical challenges - delayed growth and development, late puberty, stunting/wasting, malnutrition, etc. Added to this are many other challenges related mainly to disclosure of HIV status, developmental delay, and transition from pediatric to adult care, including the choice of appropriate treatment regimens and adherence. Psychological and social factors deeply impact the ability to deal with the illness and must be addressed at all levels to encourage and support this vulnerable group.

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 rates of syphilis among STI patients are contributing to the spread of HIV-1 in India.

BACKGROUND: Recent syphilis outbreaks have raised concern regarding the potential enhancement of HIV transmission. The incidence of syphilis and its association with HIV-1 infection rates among a cohort of sexually transmitted infection (STI) clinic attendees was investigated. METHODS: 2732 HIV-1 seronegative patients attending three STI and one gynaecology clinic, were enrolled from 1993-2000 in an ongoing prospective cohort study of acute HIV-1 infection in Pune, India. At screening and quarterly follow up visits, participants underwent HIV-1 risk reduction counselling, risk behaviour assessment and HIV/STI screening that included testing for serological evidence of syphilis by RPR with TPHA confirmation. Patients with genital ulcers were screened with dark field microscopy. RESULTS: Among 2324 participants who were HIV-1 and RPR seronegative at baseline, 172 participants were found to have clinical or laboratory evidence of syphilis during follow up (5.4 per 100 person years, 95% CI 4.8 to 6.5 per 100 person years). Independent predictors of syphilis acquisition based on a Cox proportional hazards model included age less than 20 years, lack of formal education, earlier calendar year of follow up, and recent HIV-1 infection. Based on a median follow up time of 11 months, the incidence of HIV-1 was 5.8 per 100 person years (95% CI 5.0 to 6.6 per 100 person years). Using a Cox proportional hazards model to adjust for known HIV risk factors, the adjusted hazard ratio of HIV-1 infection associated with incident syphilis was 4.44 (95% CI 2.96 to 6.65; p<0.001). CONCLUSIONS: A high incidence rate of syphilis was observed among STI clinic attendees. The elevated risk of HIV-1 infection that was observed among participants with incident syphilis supports the hypothesis that syphilis enhances the sexual transmission of HIV-1 and highlights the importance of early diagnosis and treatment of syphilis.

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.