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R C Bollinger

Publications and source records attributed to R C Bollinger.

35 records · Page 2Linked to original sources
PubMed1997

Risk factors and clinical presentation of acute primary HIV infection in India.

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. OBJECTIVES: 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. DESIGN AND SETTING: Nested case-control study in Pune, India. PARTICIPANTS: HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996. OUTCOME MEASURES: Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection. RESULTS: 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. CONCLUSIONS: 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.

AIDS Serodiagnosis↗
PubMed1997

Spread of HIV infection in married monogamous women in India.

CONTEXT: 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. OBJECTIVE: 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. METHODS: 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. MAIN OUTCOME MEASURE: Prevalence and risk determinants of HIV infection. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed1997

Characterization of a polyclonal cytolytic T lymphocyte response to human immunodeficiency virus in persons without clinical progression.

A total of 82 human immunodeficiency virus (HIV)-1-specific cytolytic T lymphocyte (CTL) clones were isolated and characterized from 5 HIV-infected subjects, utilizing multiple HLA class I alleles. B62-restricted, HIV-1 gag-specific CTL clones isolated from a single blood sample from 1 subject used four different Vbeta gene rearrangements. Multiple CTL clones could be isolated from the same time point directed against HIV-1 gag, nef, and env from 1 subject. A prospective analysis resulted in the isolation of CTL clones from 1 subject directed against multiple HIV-1 antigens, including the same highly conserved nef peptide, over a 1-year period, in the absence of detectable circulating viral plasma RNA. These data suggest that in some persons without clinical progression and low levels of circulating HIV-1, the CTL response is polyclonal, is directed against multiple HIV-1 proteins, including highly conserved peptides within these proteins, and is maintained over time.

Antigens, Viral↗
PubMed1996

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.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The human immunodeficiency virus epidemic in India. Current magnitude and future projections.

Since the first case of the human immunodeficiency virus (HIV) infection was documented in India in 1986, there has been an explosive increase in HIV transmission. In this review we describe the chronology of the HIV epidemic in India, preliminary information about the clinical presentation of the acquired immunodeficiency syndrome (AIDS), the biological and behavioral aspects of HIV transmission in the Indian setting, and projections regarding the future of the HIV epidemic in India. Using recent data obtained by searching the computerized literature and published abstracts, conference proceedings, and publications from the government of India, we show that India is experiencing a major epidemic of HIV transmission in high-risk populations of commercial sex workers, sexually transmitted disease clinic patients, intravenous drug users, and commercial blood donors. There is also evidence of recent spread of the epidemic from these high-risk groups to other risk groups in India, and from urban centers to rural populations. It is estimated that 1.6 million people are currently infected with HIV in India. At the present rate of transmission, India will have the largest number of HIV-infected individuals of any country in the world by the end of this decade, with more than 5 million infected individuals. Because limited data are available, comprehensive and well-designed epidemiologic surveys are urgently needed to adequately characterize the HIV epidemic in India and to help implement targeted and effective educational and prevention-oriented programs.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A novel method for detection and ex vivo expansion of HIV type 1-specific cytolytic T lymphocytes.

Studies have shown that cytolytic T lymphocyte (CTL) responses may be critical to the clearance of the early viremia in acute HIV-1 infection. It is likely that these cells play an important role in prolonging the asymptomatic phase of the infection. Although HIV-1-specific CTL activity can be detected in direct assays of freshly isolated peripheral blood lymphocytes (PBL) from some infected individuals, this method fails to detect CTL that are present at low frequency and resting, memory CTL. For these reasons, direct CTL assays on PBL from seropositive individuals may underestimate the level of CTL immunity. As part of ongoing investigations of CTL activity in HIV-1-infected individuals, we developed a novel strategy for the detection and ex vivo expansion of HIV-1-specific CTL. This technique involves selective stimulation of PBL from seropositive individuals with autologous Epstein-Barr virus (EBV)-transformed, B-lymphoblastoid cell lines (B-LCL) infected with vaccinia vectors expressing various HIV-1 genes. Prior to their use for in vitro stimulation, B-LCL are treated with psoralen and UV light to inactivate vaccinia virus. After 1 week of stimulation, CTL activity in stimulated cultures is measured in a standard 51Cr release assay. This ex vivo expansion method can selectively increase the bulk culture CTL activity against env, gag and nef, even in some seropositive individuals with low CD4 counts and little evidence of HIV-1-specific CTL in assays of freshly isolated PBL. These expanded CTL are predominantly of the CD8+ phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Separation↗
PubMed1993

Transporter-independent processing of HIV-1 envelope protein for recognition by CD8+ T cells.

CD8+ cytolytic T lymphocytes (CTL) identify virally infected cells by recognizing processed viral antigen in association with class I major histocompatibility complex (MHC) molecules on infected cells. Processing begins in the cytosol with the generation of peptides, possibly by a protease complex with MHC-encoded subunits, known as the proteasome. Transport of the resulting cytosolic peptides into the endoplasmic reticulum for association with class I molecules is essential and probably involves a heterodimer of the MHC-encoded proteins, Tap-1 and Tap-2. The site of processing of viral envelope proteins is uncertain. These proteins are not present in the cytosol because of cotranslational translocation into the endoplasmic reticulum. We show here that the HIV-1 envelope (env) protein is processed in infected cells by a novel Tap-1/Tap-2-independent pathway that seems to be localized to the endoplasmic reticulum.

Antigen-Presenting Cells↗
PubMed1993

Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes: effects on viral replication.

Cytolytic T lymphocytes (CTLs) specific for the human immunodeficiency virus (HIV-1) envelope glycoproteins have been cloned from HIV-1-seronegative human volunteers immunized with HIV-1 gp160-based candidate vaccines. Although vaccine-induced CTLs can potentially contribute to the antiviral response by direct lysis of infected cells, these CTLs may also produce cytokines that alter HIV-1 gene expression in other infected cells present in the microenvironment where CTL-target cell interactions occur. Vaccine-induced CTL clones were therefore examined for production of cytokines that affect HIV-1 gene expression in chronically infected T lymphocytic and promonocytic cell lines. Enhancement of HIV-1 gene expression was observed with supernatants from CD4+ CTL clones and with supernatants from a subset of CD8+ CTL clones. For each clone studied, upregulation of HIV-1 gene expression in chronically infected T cell lines resulted from the antigen-specific release by CTLs of tumor necrosis factor alpha (TNF-alpha). CD4+ and CD8+ CTLs that released TNF-alpha on antigen stimulation were also shown to express a biologically active 26-kDa transmembrane form of TNF-alpha, which was sufficient to induce upregulation of HIV-1 gene expression in chronically infected T cells placed in direct contact with the CTLs. Supernatants from antigen-activated, vaccine-induced CD4+ and CD8+ CTLs also caused upregulation of HIV-1 gene expression in chronically infected promonocytic cells. A subset of CD8+ CTL clones also produced a soluble factor(s) that inhibited HIV-1 replication in acutely infected autologous CD4+ blasts. Supernatants from CD4+ CTLs had no effect on HIV-1 replication in acutely infected CD4+ blasts. These results suggest that cytokine production as well as cytolytic activity should be evaluated in the analysis of the potential antiviral effects of vaccine-induced CTLs.

AIDS Vaccines↗
PubMed1992

Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines.

The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1-specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8+ CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120-specific, CD4+ CTL.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Vaccines↗
PubMed1992

Clonal analysis of T-cell responses to the HIV-1 envelope proteins in AIDS vaccine recipients.

Both CD4+ and CD8+ CTL responses specific for the HIV-1 envelope proteins can be elicited in seronegative humans by candidate AIDS vaccines. The phenotype of the responding CTL depends upon the nature of the vaccine, with CD8+ CTL being found exclusively in recipients of live virus vaccines. Both types of CTL are active against HIV-1-infected cells in vitro. However, the potential efficacy of vaccine-induced CTL in preventing infection in vaccinated individuals exposed to HIV-1 is unknown and is likely to be dependent upon complex factors including lytic activity against divergent strains, cytokines produced, and the lysis of noninfected CD4+ T cells.

AIDS Vaccines↗
PubMed1992

Acid dissociation increases the sensitivity of p24 antigen detection for the evaluation of antiviral therapy and disease progression in asymptomatic human immunodeficiency virus-infected persons.

Because the time from primary infection to symptoms in human immunodeficiency virus type 1 (HIV-1) infection is typically 8-10 years, the use of surrogate markers to monitor disease progression and therapeutic efficacy is of interest. An acid dissociation procedure that disrupts the p24 antigen-antibody complexes found in early HIV-1 infection has greatly increased the sensitivity of p24 detection assays. The utility of p24 antigen after acid treatment as a surrogate marker of disease progression and therapeutic effect in asymptomatic HIV-infected subjects receiving zidovudine (AZT) was determined. After acid treatment, the sensitivity of p24 antigen detection increased fivefold. The proportion of subjects who were antigenemic increased over the 48-week follow-up in the placebo group; approximately 50% of subjects who were p24 antigen-positive at entry and who received AZT showed clearance or a greater than 50% reduction in baseline p24 antigen levels at 16 and 32 weeks. Thus, acid treatment of plasma may allow the use of p24 antigen as a marker of disease progression and therapeutic response.

Cohort Studies↗
PubMed1991

Antibody-mediated clearance of alphavirus infection from neurons.

Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. Three monoclonal antibodies to two different epitopes on the E2 envelope glycoprotein mediated viral clearance. Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. Thus, antibody can mediate clearance of alphavirus infection from neurons by restricting viral gene expression.

Alphavirus↗
PubMedDate not supplied

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.

Acquired Immunodeficiency Syndrome↗