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C R Rinaldo

Publications and source records attributed to C R Rinaldo.

At least 73 records · Page 4Linked to original sources
PubMed1993

Random depletion of T cells that bear specific T cell receptor V beta sequences in AIDS patients.

A cross-sectional PCR analysis of the TCR V beta repertoires in HIV-1 seronegative controls and HIV-1 infected individuals with either clinically or immunologically defined AIDS [1] was performed to examine the proposed superantigen model for HIV-1 pathogenesis. In contrast to previous reports, we find neither uniform specific losses nor uniform clonal expansions of particular TCR V beta gene families in subjects with AIDS. Instead our study, which was designed specifically to qualitatively determine the presence or absence of TCR V beta families in both subject populations, indicates an overall diminution in the expression of TCR V beta gene families in HIV-1 infected individuals with AIDS compared with controls. This is commensurate with the decrease in CD4 T cells in the AIDS population. Our data are therefore not directly suggestive of a common superantigen model of HIV-1 induced T cell clonal depletion or anergy, but instead emphasize a broad decrease in signals throughout the TCR V beta repertoire in AIDS versus control groups. This random depletion in the TCR V beta repertoire is most likely caused by aspects of HIV-1 pathogenesis other than virus-encoded superantigens.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein.

Previously we reported that synthetic peptide homologs of an amphipathic region (designated the lentivirus lytic peptide, or LLP-1) near the carboxy terminus of HIV-1 transmembrane protein (TM) were toxic for both prokaryotic and eukaryotic cells when added exogenously to cell cultures. We postulated that these peptides may exert their toxic effects in much the same manner as natural cytolytic peptides such as magainins, cecropins, and melittin by forming pores through cellular membranes. Here we show the results of 51Cr-release assays and membrane flux measurements of peptide treated cells that support our hypothesis. We have also tested a limited panel of LLP-1 peptide analogs in these assays and found that relatively minor alterations in peptide charge or amphipathicity in the parent HIV LLP-1 sequence resulted in total loss of membrane perturbative properties. These results demonstrate that the peptide homolog of HIV-1 LLP-1 can indeed perturb membranes by forming pores of defined size in cytoplasmic membranes. Furthermore, the analog studies described here reveal that the amphipathy and high positive charge of this protein segment are required for the membrane perturbative properties.

Amino Acid Sequence↗
PubMed1993

Seroprevalence of HIV-1 and HIV-2 infection among children diagnosed with protein-calorie malnutrition in Nigeria.

Excessive weight loss due to protein calorie malnutrition (PCM) is a significant problem in Nigerian children. This syndrome may be difficult to differentiate from the wasting disease caused by human immunodeficiency virus type 1 (HIV-1) infection. We studied 70 children admitted to the Baptist Medical Center in Ogbomosho, Nigeria in 1990 with PCM for prevalence of antibodies to HIV-1 and HIV-2. The cohort was from low-risk mothers and had a median age of 25 months (range, 4 months-9 years) with a weight deficit of at least 20% of the theoretical weight for age. Two sera were positive for anti-HIV-1 by both ELISA and Western blot (WB). A high prevalence of samples negative for HIV-1 antibody by ELISA were repeatedly reactive (11%, 8/70) or indeterminate (46%, 32/70) by WB. None of the sera was positive for antibody to HIV-2. There was no correlation of ELISA positivity or extent of WB banding with successful recovery from malnutrition. These results indicate a relatively low but significant prevalence of HIV-1 infection in Nigerian children with PCM. The high prevalence of indeterminate reactions in WB assays for HIV-1 suggests that other procedures may be necessary for confirmatory diagnosis of HIV-1 infection in this African population.

Blotting, Western↗
PubMed1993

Changes in HIV rates and sexual behavior among homosexual men, 1984 to 1988/92.

Data were collected from 1614 homosexual and bisexual men in 1984 through 1985 and from 1988 to 1992 in Pittsburgh. Of the men entering the study since 1988, 16% reported engaging in unprotected anal receptive intercourse with more than one partner during the 6 months before their visit. Approximately 7% of the younger men and 18% of the men over 22 years of age in the recent cohort were already infected with the human immunodeficiency virus, the same rates as those described 8 years ago. Aggressive risk-reduction programs are needed in high schools and existing networks in the gay community.

Adolescent↗
PubMed1993

CD4+ lymphocyte response to zidovudine as a predictor of AIDS-free time and survival time.

It is unknown whether the early rise in CD4+ lymphocyte count seen in zidovudine-treated patients is associated with increased AIDS-free time and survival time. To determine the association of this and other changes in immunologic and hematologic markers with prognosis for time to AIDS and survival, we followed 747 AIDS-free patients from initiation of zidovudine therapy in the Multicenter AIDS Cohort Study (MACS). Participants were seen semiannually and had data collected on medication use, immunologic and hematologic variables, and clinical outcomes. AIDS was diagnosed in 216 participants and 165 died during the median follow-up period of 2.0 years. Duration of zidovudine use was categorized into 1-6 months (after 6 months of follow-up) and 7-12 months (12 months of follow-up). During the 6-month follow-up period in which zidovudine was first used, CD4+ lymphocyte levels rose by 17 cells/microliters compared with a mean decrease of 30 cells/microliters/6 months in untreated individuals (after adjusting for baseline CD4+ lymphocyte count). Baseline levels of CD4+ lymphocytes, platelets, and hemoglobin were significant predictors of AIDS and death. After 1-6 months with patients taking zidovudine and controlling for baseline (pretreatment) variables, change in markers after 6 months of follow-up and use of Pneumocystis carinii pneumonia prophylaxis and other antivirals, change in CD4+ lymphocyte count significantly predicted progression to AIDS [relative hazard (RH) = 0.71 for each 100 cell/microliters increase, p = 0.0001] and survival (RH = 0.78 per 100 cell/microliters increase; p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cell-mediated immunity and immunosuppression in herpes simplex virus infection.

Innate and adaptive forms of cellular immunity have important, interactive roles in host resistance to herpes simplex virus (HSV) infection. Hence, suppression of non-HSV specific and anti-HSV specific cellular immune responses can predispose the host to severe HSV infection. Studies using depletion and adoptive transfer of selected subpopulations of NK cells, macrophages, and CD4+ and CD8+ T lymphocytes indicate that each of these is of significance in protection against infection with HSV. Further evidence suggests that cytokines such as interferons alpha and gamma, interleukin 2 and leukocyte migration inhibition factor also have central roles in these cell functions during HSV infection. Of importance is that HSV itself can result in transient suppression of several innate and adaptive cellular immune responses during acute episodes of infection in normal adults. Mechanisms by which HSV may mediate this immune dysfunction include enhanced activity of suppressor T cells and soluble suppressor factors, decreases in cytokine production, decreases in expression of major and minor histocompatibility antigens and direct inhibition of cytotoxic effector cell function. Knowledge of anti-HSV cellular immunity and of the immunosuppressive properties of HSV are of importance in the development of appropriate treatment and vaccine strategies for this herpesvirus.

Animals↗
PubMed1992

Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.

The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The effects on survival of early treatment of human immunodeficiency virus infection.

BACKGROUND: Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. METHODS: We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS: After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). CONCLUSIONS: The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1992

A phase I study of ampligen in human immunodeficiency virus-infected subjects.

Ampligen, poly(I)n:poly(C12U)n, was administered intravenously to 39 human immunodeficiency virus (HIV)-infected subjects, asymptomatic or with early AIDS-related complex (ARC) and with CD4+ cell counts less than 500/mm3 in a phase I dose-escalation study. Six doses ranging from 10 to 570 mg/m2 were administered twice-weekly for 9-25 weeks to groups of 5-7 subjects. There was no significant effect on HIV as measured by serum p24 levels, the proportion of patients from whom HIV could be cocultured from blood, or the concentration of peripheral mononuclear cells positive for the virus. Although patients on 10 and 40 mg/m2 showed a significant decline in CD4+ cell counts, as would be expected in untreated patients, patients who received doses greater than or equal to 120 mg/m2 showed no significant decline in CD4+ cell counts. In addition, there was a significant increase in CD4+ cell counts with respect to dose of ampligen. This effect of ampligen and the fact that it has been shown to act synergistically with zidovudine against HIV in vitro suggest that the combination might be tried clinically in patients.

AIDS-Related Complex↗
PubMed1992

Frequent oropharyngeal shedding of Epstein-Barr virus in homosexual men during early HIV infection.

OBJECTIVE: To determine the frequency of Epstein-Barr virus (EBV) oropharyngeal shedding during HIV infection in homosexual men in the Multicenter AIDS Cohort Study. DESIGN: The cohort consisted of 210 men who were HIV-seronegative at their baseline study visit, 39 of whom seroconverted to HIV at a later date, and 73 asymptomatic and mildly symptomatic men with HIV infection of indeterminate duration. METHODS: EBV in throat washings was detected by transformation of newborn cord blood lymphocytes. RESULTS: EBV was isolated from 49% (35 out of 71) of the HIV-seropositive and 16% (33 out of 204) of the HIV-seronegative homosexual men tested at their baseline visit. Elevated EBV shedding frequency was noted 6 months before, as well as during the first HIV-seropositive clinic visit, in the men who seroconverted to HIV. Seronegative men who shed EBV at their baseline visit seroconverted to HIV within a shorter period than did non-shedders during 5 years of follow-up. Shedding of EBV was not significantly associated with either abnormal T-cell numbers, clinical symptoms or risk for development of AIDS. CONCLUSIONS: There is an increased rate of EBV shedding in HIV-seropositive homosexual men that occurs very early in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Enhanced shedding of cytomegalovirus in semen of human immunodeficiency virus-seropositive homosexual men.

Site-specific shedding of cytomegalovirus (CMV) was assessed in a longitudinal study of homosexual and bisexual men. At initial testing, CMV was cultured from the semen of 33% (19 of 58) of asymptomatic and mildly symptomatic men who were seropositive for human immunodeficiency virus (HIV) at the time of entry into the study, whereas it was cultured from the semen of 17% (10 of 58) of the men who were HIV seronegative. CMV was isolated much more frequently from semen than from urine or throat washing specimens, and it was rarely recovered from stool or blood, regardless of the subject's HIV serostatus. CMV was cultured from the semen of 31% (16 of 52) of the men relatively early after seroconversion to HIV (mean, 12.8 months). CMV was persistently isolated from the semen of a greater proportion of the HIV-seropositive men than from the semen of the HIV-seronegative men during a 4.5-year follow-up period (52 of 110 - [47%] and 15 of 58 [26%] men, respectively). There was an increased relative risk for shedding of CMV in semen in association with decreased CD4+ cell numbers and increased levels of serum immunoglobulin A. However, there was no association of CMV shedding with an increased risk for the development of AIDS.

Adolescent↗
PubMed1992

Guidelines for disclosing HIV-antibody test results to clients.

Because of new preventive therapies, HIV-antibody testing of asymptomatic individuals now has clear clinical benefits. Consequently, greater numbers of individuals are expected to seek testing. This article, based on the authors' experiences with disclosing HIV-antibody test results to a high-risk group of men, makes recommendations for how best to present HIV-antibody results. Disclosing HIV-antibody results provides an educational opportunity as well as a psychological challenge for clinicians. Some unusual client reactions are detailed in the case studies.

Adult↗
PubMed1991

Temporal trends in human immunodeficiency virus type 1 seroconversion 1984-1989. A report from the Multicenter AIDS Cohort Study (MACS).

The 5-year temporal trends in human immunodeficiency virus type 1 (HIV-1) seroconversion between 1984 and 1989 among homosexual/bisexual men participating in the Multicenter AIDS Cohort Study (MACS) are reported. Of 3,262 initially seronegative men, 368 (11.3%) had seroconverted by December 31, 1989. Although the incidence of seroconversion declined precipitously during the first 3 years of follow-up (from 4.1% to 0.9% per 6 months), no evidence for a further substantial reduction was noted after mid-1987, since 6-month incidence rates ranged between 0.5% and 1.2%. The Chicago cohort experienced an increase in HIV-1 seroconversion during both semesters of 1989; 2.1% and 1.6% per 6 months, respectively, became newly infected. Other MACS centers did not report such an increase. Center-specific differences were observed by race; black men were at higher seroconversion risk than white men in Baltimore/Washington (relative risk (RR) = 3.4) and Chicago (RR = 2.4), while Hispanic men were at higher risk than white men in Chicago (RR = 3.3). Younger age (less than 35 years) was also associated with HIV-1 seroconversion (RR = 1.5). It is disturbing to report an overall annual seroconversion rate of 1.2% for the 2 years prior to December 31, 1989, as well as evidence for a sustained recent increase in Chicago during 1989. Long-term maintenance of safe-sex behaviors should be the cornerstone of acquired immunodeficiency syndrome prevention among homosexual/bisexual men.

Age Factors↗
PubMed1991

Cytomegalovirus IgG and IgA serum antibodies in a study of HIV infection and HIV related diseases in homosexual men.

The significance of serum IgG and IgA antibodies to cytomegalovirus (CMV) at various stages of human immune deficiency virus (HIV) infection was studied in 175 homosexual men. Sera were obtained from 123 HIV seropositives [41 asymptomatic, 29 with lymphadenopathy associated syndrome (LAS), 22 with AIDS related complex (ARC), and 31 AIDS patients], 17 HIV seroconverters, and 35 HIV asymptomatic seronegatives. The sera were tested blindly for CMV IgA and IgG antibodies using the immunoperoxidase assay (IPA) and CMV infected human embryo cells. Cross-sectional analysis of CMV IgG antibodies at a titer of greater than or equal to 20 showed 87% and 100% prevalence in the HIV seronegative groups and in the HIV seropositive groups, respectively (P less than 0.05). CMV IgG antibodies at a titer of greater than or equal to 80 were present in significantly higher proportions among the HIV seropositive subjects of the various groups as compared with the HIV seronegative homosexual men. However, in the HIV seronegatives who later seroconverted to HIV, a significantly higher prevalence of CMV antibodies (35%) was detected before HIV seroconversion, as compared with the persistently HIV seronegative subjects (14.3%) (P less than 0.05). The HIV seronegatives pre-HIV seroconversion also exhibited a significantly higher geometric mean titer (GMT) of CMV IgG antibodies (62.17 +/- 0.64) as compared with the persistently HIV seronegatives (34.0 +/- 0.6) (P = 0.03). Significantly higher GMTs of CMV IgG antibodies were detected in all the HIV seropositive groups as compared with the persistently HIV seronegative group. CMV IgG antibodies were not detected in the HIV seronegative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV.

Antibodies, Viral↗
PubMed1991

Zidovudine use in AIDS-free HIV-1-seropositive homosexual men in the Multicenter AIDS Cohort Study (MACS), 1987-1989.

Zidovudine use data were examined in the Multicenter AIDS Cohort Study to determine (i) if the proportion of pre-AIDS participants (i.e., CD4+ cells less than 200/mm3 or AIDS-related complex) taking zidovudine is high enough to explain a slower than expected rise in AIDS incidence in U.S. homosexual men since mid-1987; (ii) which factors are associated with starting zidovudine and clinical trials of zidovudine; and (iii) if pre-AIDS patients, as a group, are being undertreated. Data on zidovudine use, clinical trial participation, and sociodemographic, clinical, and hematologic variables were collected every 6 months from 1,195 AIDS-free HIV-1-seropositive homosexual men from April 1987 to September 1989. Overall prevalence of zidovudine use rose from 3.6% in mid-1987 (visit 7) to 23% in mid-1989 (visit 11). Of those with less than 200 CD4+ lymphocytes/mm3, the prevalence of zidovudine use rose from 23% (24% if those taking zidovudine or placebo as part of a clinical trial are included) at visit 7 to 58% (69%) at visit 11. Of those with ARC, 20% (23%) were using zidovudine at visit 7 and 55% (65%) at visit 11. Although numbers were small, the advanced ARC participants (CD4+ cells less than 200/mm3 and two or more symptoms) reported the highest treatment rates (50, 78, 80, 60, and 74% at visits 7-11, respectively). By September 1989, 42% (31%) of those with CD4+ lymphocyte levels less than 200/mm3 were still not receiving zidovudine, suggesting that many high-risk, pre-AIDS individuals are being undertreated. To explore this finding further, we examined a range of sociodemographic, hematologic, and clinical variables to determine which factors best predicted initiation of zidovudine therapy outside of clinical trials. In multivariate analyses, CD4+ lymphocyte number was the most consistent predictor of initiation of therapy over all four study visits. For each 100 cells/mm3 deficit, the odds ratios were 2.3 (95% C.I. of 1.7-3.1) at visit 7 and 1.7% (95% C.I. of 1.4-2.0) at visit 11. Symptom status and education level were also associated with starting zidovudine, but not at all visits. The relatively low predictive power of the clinical variables raises and the possibility that nonclinical factors not measured in the MACS (drug cost, third-party insurance restrictions, and individual preferences) may play an important role in predicting zidovudine use. Finally, comparisons were made between seropositive participants starting clinical trials of zidovudine and the rest of the study population. No important differences were found in demographic or major clinical variables between clinical trial participants and zidovudine nonusers in this study.

AIDS-Related Complex↗
PubMed1990

Sexual transmission efficiency of hepatitis B virus and human immunodeficiency virus among homosexual men.

The relative sexual transmission efficiency of hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) was investigated by a prospective study of homosexual men in Pittsburgh, Pa, from the Multicenter AIDS Cohort Study. During the 30-month follow-up, 19.8% and 7.8% of the initially seronegative HBV and HIV-1 groups were estimated to seroconvert to HBV and HIV-1, respectively. The significantly higher cumulative HBV seroconversion rate occurred despite a much lower prevalence of hepatitis B carriers (7% were hepatitis B surface antigen positive) compared with HIV-1 carriers (22% were HIV-1 antibody positive). The sexual exposure profile of HBV and HIV-1 seroconverters was similar during the 6 months prior to seroconversion, supporting the link between anal intercourse and acquisition of either infection. However, insertive, not receptive, anal intercourse was the major risk factor identified for HBV seroconversion, suggesting that transurethral exposure is an important mode of transmission. These data suggest that HBV is transmitted 8.6-fold more efficiently than HIV-1 among homosexual men studied and underscore the benefits of both HBV immunization and use of condoms during intercourse to prevent HBV infection.

Cohort Studies↗