摘要:

Quantitative culture of human immunodeficiency virus (HIV) was performed on 121 plasma samples from 76 HIV-infected individuals to determine the sensitivity of the assay at different stages of disease and to measure the effect of antiviral therapy on plasma viremia. Plasma virus was detected in 49 of 76 (64%) of patients, primarily those with AIDS and AIDS-related complex (36 of 38) versus asymptomatic subjects (13 of 38) (p< 0.001, X2). Similarly, plasma cultures were more often positive in patients with < 250 CD4+T cells per μl (38 of 40) than in those with > 250 CD4+T cells per μl (11 of 36) (p< 0.001, X2). Plasma virus cultures were also more likely to be positive in patients with detectable serum p24 antigen (24 of 26) than in those without detectable p24 antigen (25 of 50) (p= 0.0023, X2). An effect of zidovudine (ZDV) treatment on plasma viremia was seen in a comparison of treated and untreated patients with < 250 CD4+T cells per μl. Geometric mean titers of plasma viremia from 16 patients treated with ZDV for more than 3 months were significantly lower than titers from 24 untreated patients (101,3versus 102,1,p< 0.05. Student'sttest. A comparison of pre- and posttherapy titers in 33 patients receiving antiviral treatment showed that plasma virus was not detectable at either time in 17 patients; there was a fall in plasma virus titer in 12; and titers were unchanged or increased in 4. In patients with advanced disease, plasma viremia is a potential marker of antiviral drug activity.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We have used the polymerase chain reaction (PCR) to detect HIV proviral sequences in minute amounts of peripheral blood collected onto newborn screening blotters. Forty-three newborns, infants, and children of HIV-infected mothers were serially studied: dried blood spot (DBS) specimens were processed for PCR; serum was assayed for HIV antibodies, p24 antigen, and immunoglobulins; mononuclear cells were cultured and CD4 cells were quantitated by immunofluorescence. There was excellent agreement between the results of blood spot PCR, viral culture, and clinical and immunological indicators of HIV infection. Eighteen of 19 infected children tested positive by both PCR and culture, including six asymptomatic infants who were < 10 weeks of age. As expected, p24 antigen capture assays were insensitive, detecting only 13 of the 19 infected children. One infected infant tested positive by PCR, but negative by culture and antigen. This infant was seropositive at 27 months and had pronounced hypergammaglobulinemia in association with nonspecific symptoms. Twenty-four of the 43 infants were asymptomatic with normal immune profiles, declining antibody levels and no evidence of infection. These children tested repeatedly negative by PCR, culture, and p24 antigen assays. Our results indicate that DBS PCR is a sensitive, specific, and cost-effective alternative to viral culture for the early diagnosis (or exclusion) of perinatal HIV infection. DBS sampling opens the way for large-scale prospective studies to determine the exact rates of vertical HIV transmission in industrialized, as well as, nonindustrialized countries.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The antiviral drug zidovudine (ZDV) slows progression to AIDS and improves survival after AIDS diagnosis. Although clinical trials have demonstrated early improvement in CD4 lymphocyte number with ZDV, long-term effects of ZDV on CD4 in advanced and asymptomatic disease are not well known. The purpose of this study was to quantitate the effect of ZDV on the natural history of HIV infection, specifically the type and frequency of new AIDS cases, AIDS-free survival, survival after AIDS, and long-term change in an immunologic marker, CD4 number, in hemophiliacs. A cohort of 84 HIV(+) hemophiliacs for whom seroconversion dates and clinical outcomes are known was prospectively observed for the time to AIDS, pattern of primary AIDS diagnosis, rate of fall in CD4 lymphocyte levels AIDS-free survival, and survival after AIDS diagnosis. The frequency of new AIDS cases has slowed since 1989. withPneumocystis cariniipneumonia (PCP) less common (15 vs. 52%,p< 0.04) and non-PCP opportunistic infection more common (54 vs. 20%,p< 0.07) than prior to 1989. Patients treated with ZDV before AIDS was diagnosed (n = 39) experienced a longer AIDS-free survival than untreated patients (n = 45), as 25% progressed to AIDS by 8.2 years compared with 4.5 years, respectively,p= 0.0013. Median survival after AIDS among those untreated was significantly shorter than among those treated with ZDV either before or after AIDS was diagnosed, 0.5, 2.8, and 2.1 years, respectively,p= 0.0005. Despite these clinical advantages, there was little difference in the rate of fall in CD4 lymphocyte number between ZDV-treated and untreated groups. The use of ZDV is associated with a changing natural history of human immunodeficiency virus infection, with longer AIDS-free survival, improved survival after AIDS diagnosis, and a slowing in new AIDS cases. These clinical advantages are not strongly related to the rate of decline in CD4 lymphocyte number.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We have investigated plasma levels of endothelial cell products playing a role in hemostasis in 125 HIV-positive patients and 30 controls. Antigenic von Willebrand factor increased significantly with disease progression and was closely correlated with CD4+cell counts and β2-microglobulin levels. Tissue-type plasminogen activator was normal in CDC II/III and CDC IVC2 patients and was slightly increased in AIDS patients, whereas plasminogen activator inhibitor was increased in each group, the stage of the disease not having any effect. Mean total protein S levels were lower in HIV-positive patients and, in 27.2% of the cases, were associated with a decrease in free protein S levels. Such abnormalities could be responsible for a hypercoagulable state in these patients and could be explained by endothelial cell damage during HIV infection. Whether this injury is due to HIV itself remains to be further investigated.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To assess the importance of the autopsy in HIV-1 infection, we retrospectively reviewed the autopsy reports of 70 HIV-1-seropositive patients at Howard University Hospital. Of the 58 patients with AIDS, the diagnosis of AIDS was made after autopsy in 24 (41%) cases. The lung was the most common site of AIDS-diagnostic diseases, and was affected in 90% of patients.Pneumocystis cariniiinfection was the most common AIDS-diagnostic disease, and was present in 50% of the AIDS patients. Thirty-eight percent of AIDS diagnostic diseases were diagnosed antemortem, including 15 of the 29Pneumocystis cariniiinfections. Most of the AIDS-diagnostic diseases were disseminated at autopsy and two or more diseases were found in some organs. Overall,Pneumocystis cariniipneumonia was the most common cause of death, accounting for a mortality of 43% among AIDS patients. Bacterial infections were common and contributed to the mortality and morbidity of both AIDS and non-AIDS patients. Bacterial infection was the cause of death in 15 AIDS and 9 non-AIDS patients. The clinical cause of death concurred with the pathological cause in 53% of our cases.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We retrospectively assessed the efficacy of maintenance therapy with pyrimethamine alone in 38 patients with AIDS and central nervous system (CNS) toxoplasmosis. The diagnosis was based on clinical presentation and compatible CT scan abnormalities with subsequent response to therapy. Survival analysis was performed by the product limit method of Kaplan-Meier. Fourteen patients received maintenance therapy with 25 mg pyrimethamine per day (group 1), and 24 patients were treated with 50 mg per day (group 2). The median survival from initiation of maintenance therapy until death or end of the study for the entire study population was 32 weeks. Median survival in group 1 was 28 weeks, as compared with 36 weeks in group 2 (p = 0.34). Relapses occurred in 12 patients, six in group 1 and six in group 2. There was no significant difference in failure-free survival between the two treatment groups (p = 0.09). One patient in group 1 and two patients in group 2 experienced severe toxicity, requiring discontinuation of therapy. All three patients relapsed and died. Two patients in group 2 who stopped treatment on their own initiative also had relapses. Thus, all five patients who discontinued therapy had relapses. Five of 13 patients in group 1 and two of 20 patients in group 2 relapsed during continuous therapy with pyrimethamine (p = 0.13); these seven patients responded to reintroduction of combination therapy (n = 6) or treatment with 50 mg pyrimethamine per day (n = 1). The results of our retrospective analysis suggest that maintenance therapy with oral pyrimethamine, 50 mg per day, in AIDS patients with CNS toxoplasmosis is effective.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A hypothesis is presented in which the immunodeficiency and cell loss leading to acquired immune deficiency syndrome and the clonal deletion associated with immunologic tolerance occur through a common mechanism. In a previous publication we proposed that the interaction of human immunodeficiency virus (HIV) with CD4 delivers activation signals that disrupt immune system regulation. In this article, we compare the biology of HIV infection with recent discoveries concerning the “two-signal” molecular mechanism for thymic selection. We propose that two-signal activation is normally followed by clonal expansion and the programmed death of most or all daughter cells through mechanisms that are proportional to the strength and duration of the activation signals. In the thymus, self-reactive cells are trapped in the continuous presence of both antigen signals (signal 1) and costimulatory signals (signal 2), leading to clonal deletion. In mature lymphocytes, we propose that HIV infection contributes a chronic high-affinity signal 2, which shifts the equilibrium of antigen-activated T-cell populations further toward programmed death. This leads to incremental memory cell deficits and gradual clonal deletion at a rate dependent on the frequency of antigen exposure and the ability of an HIV quasispecies to induce signal 2.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A method is proposed for assessing the cumulative risk of various AIDS-defining conditions as the CD4 lymphocyte count declines in HIV-infected individuals. The method is analogous to survival analysis but is based on the CD4 lymphocyte count rather than on time. Thus, the level to which the CD4 lymphocyte count has declined, rather than the length of time since seroconversion, is considered as an individual'ssurvival interval.The survival interval may be censored (due to lack of follow-up) or treated as an interval to failure (if the individual develops AIDS). The Kaplan-Meier (product-limit) estimates, of the proportion of individuals developing AIDS before reaching a given low CD4 lymphocyte count, may be useful for determining when prophylactic treatment should begin.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We investigated the association between maternal antibodies to HIV-1 peptides in pregnant women and the acquisition of HIV-1 infection by their offspring. Pregnant HIV-1-infected Haitian women were tested for the presence of antibodies against peptides of 14–17 amino acid length from the V3 loop region of strains IIIb and MN. Antibody testing was performed in two separate laboratories by enzyme-linked immunosorbent assay (ELISA). Peptides from four regions of the V3 loop were synthesized in several different laboratories and the purity confirmed by high performance liquid chromatography (HPLC). The mothers of infants who acquired HIV-1 infections did not differ significantly from the mothers of uninfected infants in the prevalence or concentration of antibodies to any of the 15 peptides evaluated. Additional studies are indicated to determine if neutralizing antibodies or other immunologic parameters are associated with maternal-infant HIV-1 transmission.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Among 5.255 active duty United States Marines on permanent tour in Okinawa, Japan, screened for human T-cell leukemia/lymphoma virus type I (HTLV-I) seropositivity, 3 (0.06%) were confirmed by Western blot analysis to have core and envelope reactivity. All three seropositive individuals have a history of prolonged sexual contact with Okinawan women, and two of the three individuals are married to seropositive Okinawan wives. Two gave a prior history of gonorrhea, while all three were negative for syphilis (MHA-TP) and hepatitis B. No other risk factors associated with HTLV-I seropositivity in the United States were identified. A banked sample from one individual, obtained 8 months after initial sexual relations with his HTLV-I-seropositive Okinawan spouse and 20 months before being retested in the survey, showed a pattern suggesting seroconversion. Although based on small numbers, these data suggest that female-to-male transmission of HTLV-I occurs in the absence of other cofactors, e.g., ulcerative genital lesions.

ISSN:0894-9255    

出版商:OVID    

年代:1992

数据来源: OVID