[Show abstract][Hide abstract] ABSTRACT: To determine if the early immunological and virological events of HIV infection are unique in a setting with limited access to health care and HIV-1 subtype C infection, we undertook a prospective cohort study to characterize the early natural history of HIV viral load and CD4(+) T lymphocyte counts in individuals with recent HIV seroconversion in India. CD4(+) T lymphocyte counts were prospectively measured for up to 720 days in 46 antiviral drug-naive persons with very early HIV infection, documented by HIV antibody seroconversion. HIV viral RNA levels were measured subsequently on reposited plasma samples from these same time points. The median viral load "set point" for Indian seroconverters was 28,729 RNA copies/ml. The median CD4(+) cell count following acute primary HIV infection was 644 cells/mm(3). Over the first 2 years since primary infection, the annual rate of increase in HIV viral load was +8274 RNA copies/ml/year and the annual decline in CD4 cell count was -120 cells/year. Although the viral "set point" was similar, the median trajectory of increasing viral load in Indian seroconverters was greater than what has been reported in untreated HIV seroconverters in the United States. These data suggest that the more rapid HIV disease progression described in resource-poor settings may be due to very early virological and host events following primary HIV infection. A rapid increase in viral load within the first 2 years after primary infection may have to be considered when applying treatment guidelines for antiretroviral therapy and opportunistic infection prophylaxis.
AIDS Research and Human Retroviruses 12/2002; 18(16):1175-9. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the prevalence and incidence of hepatitis B virus (HBV) infection among patients attending three STD clinics in Pune, India, and to identify associated risk factors.
Of the 2098 patients screened at STD clinics in Pune during 1996, 497, who returned for at least one follow up visit, were screened for various markers of HBV infection (HBsAg, anti-HBs, anti-HBc), HIV antibody, and VDRL.
Of the 497 participants 3.6%, 26.5%, and 43.2% were positive for HBsAg, anti-HBs, and anti-HBc respectively. Tattooing (AOR 1.64, 95% CI 1.03 to 2.64) was found to be independently associated with presence of core antibody. Additionally, history of being in commercial sex work and history of a genital ulcer were independently associated with a positive anti-HBc antibody test (AOR 12.45, 95% CI 5.58 to 27.82 and AOR 1.70, 95% CI 1.09 to 2.66, respectively). 72 out of 497 (14.5%) participants were HIV positive at baseline. HIV-1 antibody positive patients were more likely to have a positive anti-HBc test (69.4% v 39.0%, p<0.001). 30 out of 282 participants, negative for anti-HBc antibody at enrolment, seroconverted subsequently, resulting in an incidence of 10.86 per 100 person years (95% CI 7.2%, 14.5%) (mean and accumulated follow up of 11.7 months and 276.17 person years, respectively).
A high prevalence and incidence of HBV infection, seen in STD clinic attendees underscore the need to provide HBV vaccine to commercial sex workers and their clients in India.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Objective: To develop a pooling method for detection of viral RNA for diagnosis of acute HIV infection and estimation of HIV-1 incidence.
Methods: Sera from 700 consecutive seronegative patients attending sexually transmitted disease clinics in Pune, India, were screened individually for p24 antigen, and pooled into seven pools of 100 for detection of HIV-1 RNA by reverse transcriptase-polymerase chain reaction. HIV-1 incidence was calculated by the traditional cohort method, the p24 antigen method, and a multistage pooling method in which RNA-positive pools were re-analyzed in smaller pools.
Results: Sera from 700 individuals were grouped into seven pools of 100, of which four were positive. These four positive pools were subdivided into eight pools of 50, of which seven were positive. The seven positive pools were subdivided into 35 pools of 10, of which 10 were positive. Based on the 10 RNA-positive pools, the point estimate of HIV-1 incidence was 19.9% per year [95% confidence interval (CI), 7.3-31.8%]. Of the 700 samples analyzed for p24 antigen, eight were positive, resulting in a point estimate of incidence of 18.5%/year (8.0-36.5%). In contrast, the incidence rate based on the traditional cohort method of follow-up was lower at 9.4%/year (4.8-16.4%) due to a low follow-up rate. Testing of individual samples from the 10 RNA-positive pools identified 10 individuals with acute primary HIV-1.
Conclusion: The multistage pooling method for detection of HIV-1 RNA was more sensitive than the p24 antigen method, and was five-fold less expensive than the p24 antigen assays. Pooling samples for RNA detection was effective in estimating current incidence rates with cost savings that would be practical for use in developing countries.
AIDS 11/2000; 14(17):2751-2757. · 6.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The envelope glycoprotein of the human immunodeficiency virus (HIV) utilizes CD4 as a receptor and CCR5 and/or CXCR4 as coreceptor to gain entry into the cell. The CCR5-tropic viruses, observed early in infection, could be important in transmission and the CXCR4-tropic viruses, observed late, may play an important role in disease progression. Viruses from 40 HIV-positive, asymptomatic or symptomatic individuals in India were isolated. Of 40 isolates 39 used CCR5. Thirty-three isolates were subtype C, 3 isolates were subtype A, and 4 isolates were HIV-2. Only 1 HIV-2 isolate, from a symptomatic individual, was dualtropic. Therefore, a majority of isolates from India belonged to subtype C and all the isolates utilized CCR5 exclusively irrespective of HIV disease status.
[Show abstract][Hide abstract] ABSTRACT: 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.
The Indian Journal of Medical Research 07/2000; 111:195-8. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two HIV-2 strains were isolated from peripheral blood mononuclear cells of two HIV-2 seropositive patients with pulmonary tuberculosis by co-cultivating the cells with phytohaemagglutinin-P stimulated heterologous normal lymphocytes. Biological characterization of the isolates indicated that both isolates were syncytium inducing and induced cytopathic effect in the form of giant cells and syncytia formation in four T lymphoid cell lines. The isolates differed in their replication pattern. The isolates were confirmed as HIV-2 by nested PCR using HIV-1 and HIV-2 specific oligonucleotide primers from the env region and by supplementary tests like indirect immunofluorescence assay, syncytium inhibition assay using reference and HIV-2 reactive patients' sera, western blot and electron microscopy. Neutralization of one isolate (TB1) with two Senegal reference sera also indicated that the isolate may be related to the Senegal strain. To our knowledge, this is the first report of isolation of HIV-2 in India.
The Indian Journal of Medical Research 05/1999; 109:123-30. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
Journal of Virology 02/1999; 73(1):152-60. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:: To determine the etiology of genital ulcer disease (GUD) among patients attending sexually transmitted disease (STD) clinics in Pune, India, and to examine the relationship to HIV infection and compare the clinical diagnosis of GUD with the results of a multiplex polymerase chain reaction (M‐PCR) assay for Treponema pallidum, herpes simplex virus (HSV), and Hemophilus ducreyi infection.
Methods:: Between June 20, 1994, and September 26, 1994, 302 patients with a genital ulcer were evaluated. Clinical etiology of GUD was based on physical appearance and microbiologic evaluations which included darkfield microscopy and serology for syphilis. Swabs of each genital ulcer were tested for HSV antigen by enzyme immunoassay (Herpchek; Dupont, Wilmington, DE) and processed in a multiplex PCR assay (M‐PCR; Roche, Branchburg, NJ) for simultaneous detection of HSV, Treponema pallidum, and Hemophilus ducreyi.
Results:: Two hundred seventy‐seven men and 25 women with a median age of 25 were evaluated. The seroprevalence of HIV was 22.2%. The etiology of GUD as determined by M‐PCR was HSV (26%), H. ducreyi (23%), T. pallidum (10%), and multiple infections (7%); no etiology was identified in 34%. HIV seroprevalence was higher among those patients positive for HSV compared with other etiologies (OR = 2.1, CI: 1.2‐3.7; p = 0.01). When compared with M‐PCR, the Herpchek test was 68.5% sensitive and 99.5% specific. Darkfield detection for T. pallidum was 39% sensitive and 82% specific, in contrast to rapid plasma reagin and fluorescent treponemal antibody absorption test, which was 66% sensitive and 90% specific. Clinical diagnosis alone or in combination with basic laboratory tests showed poor agreement with M‐PCR.
Conclusions:: The etiology of GUD among STD patients in India is multifactorial with a predominance of herpes and chancroid infections. Herpes was more common among HIV‐positive individuals, possibly reflecting underlying immunosuppression. These data demonstrate that clinical diagnosis is not dependable for identification of GUD etiology especially in HIV seropositive cases. In areas where diagnostic tests are limited, a syndromic approach using antibiotics directed against both syphilis and chancroid, and where prevalent, lymphogranuloma venereum and donovanosis is recommended for patients with GUD.
Sex Transm Dis 12/1998; 26(1):55–62. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the light of the diversity of HIV, matching the genotype of candidate HIV vaccines with the transmitted genotype may be required. Alternatively, matching the immunotype of HIV vaccines and transmitted subtypes may be the best option. Since studies of cross-subtype HIV-1 immunity are limited, subtype B specific cytolytic T lymphocyte (CTL) responses were measured in subtype C infected individuals. HIV-1 subtype B-specific CTLs, plasma viral load and absolute CD4 and CD8 lymphocyte numbers were measured in six HIV-1 subtype C infected individuals within a year of seroconversion. HIV-1 subtype B env. gag and nef-specific CTL precursor frequencies were measured by limiting dilution analysis. Three of the six subjects had demonstrable CTL directed at more than one HIV-1 subtype B antigens. One individual demonstrated CTL directed against all three HIV-1 subtype B antigens, while two individuals did not demonstrate CTL against HIV-1 subtype B antigens. The frequencies of CTL precursor were not associated with plasma viral load or absolute CD4 cell counts in peripheral blood. These findings suggest that some individuals recently infected with subtype C HIV-1 generate cross-reactive CTL that are directed against HIV-1 subtype B.
The Indian Journal of Medical Research 09/1998; 108:35-41. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV infection status was determined in 302 consecutive patients with genital ulcer disease (GUD) presenting to two sexually transmitted disease (STD) clinics in Pune, India. Of the 71 (24%) individuals with HIV infection, 67 (94%) were HIV antibody-positive, and 4 (6%) were HIV antibody-negative but p24 antigen-positive at the time of presentation. HIV-1 DNA was detected in 24 (34%) specimens. The genital ulcers of all four acutely infected p24-antigenemic subjects were HIV-1 DNA-positive by polymerase chain reaction (PCR) assay, compared with 20 of 67 (30%) seropositive patients (p = .01). Presence of chancroid, GUD symptoms for > 10 days, and concurrent diagnosis of cervicitis or urethritis were significantly associated risk factors for HIV-1 DNA shedding in ulcers. Early GUD diagnosis and aggressive treatment of HIV-infected patients may significantly reduce secondary transmission of HIV to other sex partners.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 07/1998; 18(3):277-81.
[Show abstract][Hide abstract] ABSTRACT: Surveillance of the different HIV-1 subtypes has important implications for developing candidate vaccines and understanding the dynamics of HIV transmission in various populations. In this study, HIV-1 viral subtypes were determined for homologies in the V3-V5 region by heteroduplex mobility assay (HMA) in 46 patients with sexually transmitted diseases (STD) in Pune, India. Proviral DNA from peripheral blood mononuclear cells (PBMCs) from 20 recent sero-coverters and 26 HIV seropositive individuals were analyzed. Of the 46 samples analyzed, 44 (96%) were HIV-1 subtype C and one each of subtypes A and B. Further analyses revealed that 29 (66%) of the C subtype samples had maximum homology to the C3-Indian reference strain, while 15 (34%) were most homologous to the C2-Zambian strain. The C3 genotype prevailed in the majority (80%) of the seropositive individuals. Most of the C3 (Indian) strains were closely homologous to each other, while more nucleotide sequence divergence was seen in C2 samples. A higher quasispecies complexity was observed in the samples collected from seropositive individuals. These findings may have important implications for the design and testing of effective candidate HIV-1 vaccines for India.
The Indian Journal of Medical Research 01/1998; 107:1-9. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses a risk for spread of infection to other populations.
To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs.
Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed.
Prevalence and risk determinants of HIV infection.
Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (P<.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs.
Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India.
JAMA The Journal of the American Medical Association 12/1997; 278(23):2090-2. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias.
To apply a method based on measurement of prevalent HIV-1 p24 antigenemia for identification of risk factors for newly acquired HIV infection and to describe the signs and symptoms of acute HIV infection.
Nested case-control study in Pune, India.
HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996.
Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection.
Of 3874 HIV antibody-negative persons tested, 58 (1.5%) were p24 antigen positive at initial presentation to the clinics. Unprotected sexual contact with a commercial sex worker (CSW) was reported by 39 (77%) of the 51 p24 antigenemic men, compared with 131 (51 %) of 255 control men (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.2-9.6; P=.02). The presence of an active genital ulcer at the time of screening was found in 46 (79%) of the 58 p24 antigenemic men and women, compared with 137 (47%) of the 290 control subjects (AOR, 4.2; 95% CI, 2.0-9.0; P<.001). Signs and symptoms independently associated with p24 antigenemia in HIV antibody-seronegative persons included fever, which was reported by 28 (48%) of the 58 p24 antigenemic subjects, but only 52 (18%) of the 290 control subjects (AOR, 4.7; 95% CI, 2.4-9.0; P<.001). Joint pain was reported by 10% of subjects recently HIV infected, compared with 2% of the control subjects (AOR, 6.5; 95% CI, 1.7-24.8; P=.006). Night sweats were reported by 9% of the p24 antigenemic, but only 1% of the control subjects (AOR, 9.1; 95% CI, 1.7-47.6; P=.009). Overall, fever, joint pain, and/or night sweats were reported in 27 (47%) of the 58 subjects with recent HIV infection.
This systematic case-control study of p24 antigen screening in HIV-seronegative patients attending STD clinics in India identified unprotected sex with a CSW and a genital ulcer as independent risk factors associated with newly acquired HIV infection. In addition, p24 antigen positivity identified recent fever, night sweats, and arthralgias as symptoms that may be predictive of recent HIV infection. In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection.
JAMA The Journal of the American Medical Association 12/1997; 278(23):2085-9. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 4618 tuberculosis patients attending the TB clinic at the Sassoon General Hospitals, Pune between 1991 and 1996 were screened for anti-HIV antibodies. Of these 694 were found reactive in enzyme immuno assay (EIA) and 624 were further confirmed by a second test, either rapid EIA or Western blot. HIV-1 reactivity was predominant among tuberculosis patients with HIV-2 reactivity appearing only in 1995. HIV-2 seroreactivity accounted for 0.54 and 1.02 per cent of all HIV reactive samples in 1995 and 1996. HIV-1 and HIV-2 dual reactivity accounted for 1.63 and 2.04 per cent of all infections in 1995 and 1996. The overall seroprevalence of HIV among newly diagnosed tuberculosis patients rose from 3.2 per cent in 1991 to 20.1 per cent in 1996.
The Indian Journal of Medical Research 10/1997; 106:207-11. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The Indian Journal of Medical Research 01/1997; 104:327-35. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context.
—Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias.
JAMA The Journal of the American Medical Association 01/1997; 278(23):2085-2089. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the risk factors for HIV infection in patients attending clinics for sexually transmitted diseases in India.
Descriptive study of HIV serology, risk behaviour, and findings on physical examination.
2800 patients presenting to outpatient clinics between 13 May 1993 and 15 July 1994.
Two clinics and the National AIDS Research Institute, in Pune, Maharashtra State, India.
HIV status, presence of sexually transmitted diseases, and sexual behaviour.
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.
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.
BMJ Clinical Research 08/1995; 311(7000):283-6. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rodrigues JJ, Mehendale SM, Shepherd ME, Divekar AD, Gangakhedkar RR, Quinn TC, Paranjape RS, Risbud AR, Brookmeyer RS, Gadkari DA, et al. Risk factors for HIV infection in people attending clinics for sexually transmitted diseases in India. BMJ. 1995;311:283- 6
BMJ Clinical Research 01/1995; 311:283-6. · 14.09 Impact Factor