摘要:

SummaryA major problem impeding development of an effective HIV vaccine is the rapid antigenic variability that is characteristic of several envelope glycoprotein epitopes. Frequent mutations alter the composition of the most immunogenic regions of the envelope glycoprotein. We have prepared a synthetic immunogen representing the evolution of the major hypervariable epitopes on the envelope glycoprotein (gp120) of HIV-1. Five synthetic constructs, representing each of the HIV-1 gp120 hypervariable epitopes were tested for recognition by antibodies from patients infected with HIV-1 from different geographic regions worldwide. An HIV-1 human plasma panel provided a representation of the antibodies recognizing subtype-specific epitope sequences prevalent at different parts of the world. The vaccine construct was recognized by antibodies from HIV-1–positive individuals infected with subtypes A, B, C, D, E, and F. Antibodies in pooled HIV-1 patient sera from San Francisco also recognized all five constructs. This complex immunogen was recognized by antibodies in sera from individual HIV-1–positive and AIDS patients from Puerto Rico and Canada, with a strong binding to the complete vaccine and the V3 component. Altogether, our results demonstrate that antibodies from seropositive patients infected with different HIV-1 clades recognize and bind to the HIV hypervariable epitope construct vaccine preparation and its individual components.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryThe HIV-1 subtype distribution was determined in 41 HIV-positive women (∼8% of all HIV-infected women in Denmark) belonging to different risk groups. HIV p17gagandenvgene subtypes were determined by DNA sequence analysis. Five different HIV subtypes were detected across all patients. Most HIV-1–positive women of Danish origin carried subtype B viruses, and a minority had virus belonging to subtypes A or C. All injecting drug users (IDUs) were infected with HIV subtype B viruses, whereas all non-B subtypes were present in cases linked to heterosexual transmission. In contrast, all women of African origin carried non-B HIV subtypes (subtypes A, C, D, or G) regardless of transmission mode. Of these women, 21% infected with non-B HIV subtypes appeared to be infected by subtype chimeric viruses and 7% were jointly infected with viruses belonging to two different subtypes (A and C). Data demonstrate a preferential representation of non-B HIV subtypes in women infected through heterosexual contact, as well as a high degree of recombination between viruses derived from endemic areas in which several HIV subtypes predominate. Combined with the increased incidence of heterosexual transmission of HIV, the results imply that an increased subtype diversity can be anticipated in newly infected individuals.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the prevalence of human herpesvirus 8 (HHV-8) infection in men treated for HIV-1 infection in Denver, Colorado.DesignCross-sectional analysisMethodsBlood samples were obtained from 216 HIV-1–infected men. Antibody to latency-associated nuclear antigen (LANA) was detected by an immunofluorescent assay and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC) was detected by polymerase chain reaction amplification.ResultsAmong HIV-1–infected men who did not have Kaposi's sarcoma (KS), prevalence of HHV-8 infection was 46% (95% confidence interval [CI], 0.39–0.52). LANA seropositivity was common both among subjects with KS and subjects without KS (69% versus 42%;p= .06), but detection of HHV-8 DNA in peripheral blood was strongly associated with a diagnosis of KS (44% versus 10%;p= .001). In a univariate analysis of study subjects without KS, neither the odds of LANA seropositivity nor detection of HHV-8 DNA in PBMC was significant for CD4+lymphocyte count, HIV-1 virus load, the use of three drug antiretroviral regimens or the prior occurrence of non-KS AIDS-related conditions.ConclusionAlthough antibodies to HHV-8 are common among HIV-1–infected men, detection of HHV-8 DNA in PBMC is uncommon and is associated with a diagnosis of Kaposi's sarcoma.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryDelayed-type hypersensitivity (DTH) responses to intradermal recombinant HIV envelope glycoprotein (rgp160) may assess cell-mediated immune responses to HIV envelope. In three studies, DTH and lymphocyte proliferation responses to rgp160 were obtained in a total of 106 HIV-seropositive subjects with CD4+counts >400 cells/mm3. Several subjects participated in more than one study. Before immunization, DTH responses were seen in 5 of 56 (9%) of HIV-infected study subjects. After immunization with an alum-adjuvanted experimental rgp160 vaccine, DTH responses were seen in 46 of 52 (89%). Using in vitro lymphocyte proliferation activity (LPA) to rgp160 as an indication of cellular immune response, skin testing has a sensitivity of 0.75 (95% confidence Interval [CI], 0.59–0.88) and a specificity of 0.84 (95% CI, 0.72–0.92). Biopsy samples of skin that had tested positive confirmed the presence of a DTH reaction with a predominance of CD4+T cells in the perivascular, inflammatory infiltrate. Skin testing before and after immunization with candidate AIDS vaccines could provide a simple method in the field to assess new cell mediated immune responses.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryTo evaluate the effectiveness of low-dose oral &agr;-interferon (&agr;-IFN), 247 HIV-infected study subjects received placebo, Alferon LDO, Veldona, or Ferimmune in a randomized, double-blind trial. Subjects had CD4+counts between 50 and 350 cells/mm3and HIV-related symptoms at entry. Study subjects rated the severity of eight symptoms using a symptom burden index (SBI). Study endpoints included changes in SBI, weight, CD4+count, and Karnofsky score between baseline and the 24-week visit. The SBI outcome and weight were measured in 99 and 106 study subjects, respectively, at both the baseline and 24-week visits. Baseline SBI scores ranged from 5.4 to 7.9 in the four arms. No clinically important or statistically significant differences were found among the four arms with regard to SBI or weight change over the 24-week period. There were also no significant differences among the arms for CD4+cell count and Karnofsky score. Few adverse reactions were noted in any arm, and there were no significant differences between arms. Although the trial was designed to enroll 560 study subjects and was prematurely terminated because of slow accrual and discontinuations of participants, the small differences among the arms in the primary and secondary endpoints do not support claims of efficacy for the measures studied.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryIndinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1–positive patients (97% male; mean age, 46.7 ± 9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/&mgr;l or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (−93,325 ± 147,911 copies/ml) and elevations in CD4+(111 ± 103 cells/&mgr;l) and CD8+(225 ± 338 cells/&mgr;l) T cell counts. Adherent patients with baseline CD4 counts <100 cells/&mgr;l were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/&mgr;l. Adherent patients with CD4 counts <100 cells/&mgr;l did not show evidence of immune “exhaustion” because they were equal to those with CD4 counts >200 cells/&mgr;l in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryPatterns of antibody response to recombinant transactivator protein (HIV-1 tat) in serum samples from HIV-1–negative persons (n= 60), HIV-1–infected asymptomatic persons (n= 20), HIV-1–infected people with Kaposi's sarcoma (n= 25) and of people with Kaposi's sarcoma without HIV-1 infection have been analyzed. None of the healthy people had anti-tat IgG in their serum. All asymptomatic patients with HIV-1 infection were anti-tat IgG-positive. Epitope mapping revealed that these sera have anti-tat IgG to all the functional domains of tat protein. Four of the 25 HIV-1–infected patients with Kaposi's sarcoma were anti-tat IgG-positive; however, epitope analysis revealed that IgG to functional domains of tat protein, in particular to TAR-binding site, were absent. All patients with Kaposi's sarcoma without HIV-1 infection were anti-tat IgG-negative. Presence or absence of anti-tat IgG, and prevalence of different antibody profiles in different groups of patients suggest the pathophysiologic role of tat protein. Thus, a passive immunization with anti-tat IgG could be a useful strategy to influence the pathophysiologic state of the disease.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundConcerns have been raised that intravenous drug users may be less likely to start highly active antiretroviral therapy (HAART) and that adherence to therapy may be poor among this group of patients. Given the decreased mortality and incidence of AIDS-defining illnesses among patients with HIV who start HAART, this may lead to a poorer prognosis among intravenous drug users.PurposeTo compare homosexual men, intravenous drug users, and heterosexuals in EuroSIDA, a prospective European cohort of 7331 patients with HIV in terms of starting a HAART treatment regimen, immunologic and virologic response to therapy, and survival.Methods6645 patients were included in this analysis. Logistic regression and Cox proportional hazards models were used to investigate the factors associated with use of HAART regimens and survival following recruitment to the EuroSIDA study.ResultsIn a multivariate logistic regression model, intravenous drug users were significantly less likely to be receiving HAART at recruitment to EuroSIDA (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.37–0.62;p< .0001) when compared with homosexual men. Similarly, during follow-up, intravenous drug users were at a 27% reduced risk of starting HAART, after adjustment for other factors related to starting HAART (relative hazard [RH], 0.73; 95% CI, 0.64–0.82;p< .0001). There were no differences between heterosexual and homosexual patients, and similar results were found within regions of Europe (South, Central and Northern). Among those patients who started HAART, there were no significant differences between exposure groups in CD4 lymphocyte count response to HAART or virologic response to HAART. After adjustment for factors related to survival, intravenous drug users were at a small, but nonsignificant increased risk of death compared with homosexuals (RH 1.16; 95% CI, 0.99–1.38;p= .074).ConclusionsIntravenous drug users were significantly less likely to start HAART, but among those who did, response to therapy was similar to that of other exposure groups. There were no differences in risk of death. If intravenous drug users continue to use HAART less commonly than other exposure groups, it may result in a poorer prognosis, a different spectrum of AIDS-defining illnesses, and differential long-term clinical needs.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryProspective follow-up of 172 HIV-infected pregnant women and their infants was conducted at Mulago Hospital, Kampala, Uganda during 1990 to 1992. Information was collected on maternal immune status (CD4 counts or clinical AIDS), and concurrent infections with sexually transmitted diseases. Infants were observed on a follow-up basis to determine HIV infection, using polymerase chain reaction (PCR) under 15 months of age and enzyme immunoassay/Western blot for those older than 15 months. Placental membrane inflammation (chorioamnionitis and funisitis), and placental villous inflammation (villitis, intervillitis, and deciduitis) were diagnosed by histopathology. Mother-to-child HIV transmission rates were assessed, and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of transmission were estimated using women with no placental pathology or evidence of immune suppression as a reference group.ResultsThe overall mother-to-child HIV transmission rate was 23.3%. Women with no placental membrane inflammation or immune suppression had a transmission rate of 11.3%; compared with 25.5% in women with placental inflammation and no immunosuppression (adjusted OR, 2.87; 95% CI, 1.04–7.90), and 37.0% in immunosuppressed women (OR, 3.07; 95% CI, 1.42–6.67). We estimate that 34% of HIV transmission could be prevented by treatment of placental membrane inflammation in nonimmunocompromised women. Transmission rates were 40.9% with genital ulcer disease (OR, 3.57; 95% CI, 1.28–9.66). Placental villous inflammation and artificial rupture of membranes did not increase transmission rates and cesarean section was associated with a nonsignificant reduction of risk (OR, 0.70; 95% CI 0.24–2.06).ConclusionPlacental membrane inflammation increases the rate of mother-to-child HIV transmission.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesTo study weight patterns among HIV-positive men and associations of baseline HIV RNA, CD4+lymphocyte count, and serum levels of neopterin and &bgr;2-microglobulin with subsequent weight loss prior to AIDS.MethodsA cohort of 1558 homosexual men from the Multicenter AIDS Cohort Study comprised the main study population. Marker values obtained using samples from a baseline visit in 1984 to 1985 were associated with weight patterns and risk of weight loss events over 10 years of follow-up. To investigate the impact of protease inhibitor (PI) therapy on weight patterns, a separate analysis was conducted for men who initiated such therapy in 1995 to 1996.ResultsIn general, HIV-positive men demonstrated a striking tendency toward weight loss, with a rate of decline that increased over time. Distinct variations in this pattern were observed according to baseline HIV RNA levels. Each marker considered was independently predictive of weight loss events. Following use of PIs, 68 men showed a tendency toward increased weight, compared with men who did not use PIs.ConclusionsAlthough baseline virologic, immunologic, and immune activation markers all predicted weight loss events in AIDS-free HIV-positive men, HIV RNA displayed the best discrimination. Shifts in weight patterns observed in this cohort after PI therapy call for further attention to nutritional and body changes as the duration of therapy increases.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID