ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective To determine whether passive transfer of a monoclonal antibody specific for the principal neutralizing determinant in the V3 region of HIV-1IIIBgp120 can protect mice with severe combined immunodeficiency (SCID) transplated with normal human peripheral blood leukocytes (hu-PBL), designated hu-PBL-SCID mice, from subsequent challenge with the homologous viral strain.Design and methods: hu-PBL-SCID mice were given intraperitoneal injections of an anti-HIV-1 neutralizing murine monoclonal antibody (BAT123), its mouse-human chimeric form (CGP 47 439), or a control murine antibody (PNTU), at a dose of 40 mg/kg. The mice were then challenged intraperitoneally with 10 mouse infectious doses of HIV-1IIIB. Three weeks later the mice were killed, and spleen cells and peritoneal lavage collected for determination of infection by coculture for viral isolation and by detection of HIV-1 DNA using polymerase chain reaction (PCR).Results: All three antibodies had similar serum half-lives of 9–12 days. No toxicity was observed in the animals. HIV-1 was recovered by coculture from five out of the six mice given PNTU, and by PCR from two out of the six mice given PNTU, but was not recovered by either technique from any of the 12 mice given BAT123 or CGP 47 439.Conclusion: BAT123 and CCP 47 439, which are specific for the principal neutralizing determinant of HIV-1IIIBprotect hu-PBL-SCID mice from infection by this viral strain. Our findings support the use of the hu-PBL-SCID mouse as anin vivomodel for studying protection against HIV-1 infection by passive immunization with anti-HIV-1 neutralizing antibodies.AIDS 1993, 7:15–21

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To gain molecular insights into different HIV-1 strains present in two different states of India, nucleotide sequences derived from the env region of four HIV-1 strains were analysed.Design: HIV-1 was isolated from high-risk patients from the states of Maharashtra (city of Bombay) and Goa. The molecular analysis of the env region encompassed all variable domains of the external glycoprotein, gp120.Methods: Genomic DNA from cultured cells infected with each of the four Indian HIV-1 strains independently was amplified by polymerase chain reaction (PCR). PCR fragments were cloned and sequenced and a phylogenetic tree constructed.Results: All four Indian HIV-1 sequences were closely related to each other. The closest related sequence to them was from a South African isolate, HIV-1NOF, with a homology of 85–87%. In the phylogenetic tree, the Indian and the South African HIV-1 sequences cluster together and constitute a subtype different from the North American/European, Central African, Uganda/Rwanda and Northern Thailand subtypes. Interestingly, the viruses of this subtype are characterized by an additional potential N-glycosylation site C-terminal to the CD4-binding domain.Conclusion: The low variation between the HIV-1 sequences from randomly chosen individuals from high-risk cohorts in two Indian states suggests a rapid and recent spread of HIV and, possibly, introduction of the virus by the same route, most probably heterosexual transmission. The rapid spread of HIV-1 variants in India, which form a subgroup of their own together with a South African strain, necessitate consideration of thse strains in vaccine development.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To evaluate the correlation between seroreactivity to peptides corresponding to the V3 loop of the major envelope glycoprotein from different HIV-1 strains and the risk of heterosexual HIV-1 transmission.Methods: Sera from 39 infected individuals (16 transmitters and 23 non-transmitters) were tested for reactivity against synthetic peptides representing sequences of the V3 loop apex from HIV-1 strains MN, SC, WMJ2, RF and IIIB.Results: A skewed distribution in seroreactivity to RF and IIIB peptides was observed between the two groups: reactivity was more prevalent in sera from non-transmitting than from transmitting individuals. Reactivity to the MN, SC and WMJ2 peptides was very frequent and there were no differences between the two groups.Conclusion: These data suggest that antibodies reactive with a larger set of V3 apex peptides (i.e., cross-reactive antibodies) could play a role in the prevention of heterosexual transmission.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To assess the value of concentrations of soluble receptors for tumour necrosis factor (sTNFR) as markers for disease progression in HIV infection.Design: We measured concentrations of sTNFR in the serum of 32 HIV-infected male patients in various stages of disease and in 12 healthy male control subjects. Correlations between the levels of sTNFR and CD4+ lymphocyte counts were calculated.Results: Serum levels of sTNFR p55 and p75 were elevated in parallel with severity of clinical stage. sTNFR p55 levels were higher at later stages of HIV infection (Centers for Disease Control stage IV) with or without concurrent illness, whereas sTNFR p75 was already elevated in asymptomatic carriers, compared with controls. There was an inverse correlation between sTNFR concentrations and CD4+ lymphocyte counts.Conclusions: Our results suggest that sTNFR concentrations could be potential markers for disease progression in HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To investigate changes in the expression of complement receptor 2 (CR2) on B-cells from HIV-infected individuals. CR2 is the C3d/Epstein-Barr virus receptor and has been implicated in B-cell activation. Changes in its level of expression may therefore be associated with B-cell dysfunction.Design: Cross-sectional study of HIV-infected adults and age-matched control donors.Methods: The percentage expression and mean fluorescence intensity of CR2 (and three additional markers: CD19, CD69, and a standard antigen designation: HLA-DR) was measured on CD20 + B-cells using a two-color flow cytometric assay.Results: This study demonstrated a highly significant (P= 0.0001) decrease in the percentage co-expression of CR2 on CD20 + B-cells in HIV-infected individuals, compared with control donors. The mean percentage of CD20 + cells co-expressing CR2 was 71% (s.d., ± 15%) in the HIV-seropositive patients and 94% (s.d., ± 4%) in the control group. The pattern of CR2 expression in a number of the patients suggested a decrease in antigen density on the cells. Decreased expression of CR2 did not correlate with disease stage (asymptomatic, AIDS-related complex, or AIDS), nor with CD4 + T-cell percentage or absolute count, in the seropositive group.Conclusions: The evidence for a role for CR2 in B-cell activation suggests that its decreased expression, which we have demonstrated in HIV-seropositive individuals, may be associated with the B-cell dysfunction observed in HIV infection. Our finding that expression of this marker is decreased even in asymptomatic patients is consistent with reports of early B-cell defects in such individuals. Further investigation of this possible association may shed some light on both the increased incidence of bacterial infections in HIV-infected adults and children and their impaired responses to certain immunizations.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To examine and quantify the association between anal squamous intraepithelial lesions (ASIL), anal human papillomavirus (HPV) infection and immunosuppression among HIV-seropositive and HIV-seronegative homosexual men.Design: Cross-sectional study among homosexual men presenting at a community-based clinic for HIV serologic screening.Results: Anal HPV DNA was detected in 55 and 23% of 285 HIV-seropositive and 204 HIV-seronegative men, respectively, by Southern transfer hybridization (STH) [odds ratio (OR), 4.0; 95% confidence interval (Cl), 2.7–6.2], and in 92 and 78% by polymerase chain reaction (PCR) (OR, 3.1; 95% Cl, 1.6–5.8). ASIL was noted in 26% of HIV-seropositive men and in 8% of HIV-seronegative men (compared with men with negative cytologic findings: OR, 5.6; 95% Cl, 3.0–10.5), with high-grade lesions noted in 4% of HIV-seropositive and in 0.5% of HIV-seronegative men. Among HIV-infected men, ASIL, detection of specific anal HPV types, and detection of high levels of anal HPV DNA (i.e., levels of HPV DNA detectable by both STH and PCR) were all associated with immunosuppression. Nevertheless, HIV-seropositive men with CD4 counts>500 × 106/Ihad a higher prevalence of both anal HPV and ASIL than men without HIV infection. Overall, detection of HPV at high levels was associated with ASIL. However, after adjustment for level of detectable HPV DNA, the risk of ASIL among HIV-seropositive men with CD4 counts < 500 × 106/I was increased 2.9-fold (95% Cl, 1.4–6.2) over that of HIV-seropositive men with CD4 counts>500 × 106/I.Conclusion: Given the high rates of ASIL in HIV-seronegative and both immunosuppressed and non-immunosuppressed HIV-seropositive homosexual men, natural history studies are now needed to assist in the development of strategies for the detection and management of such lesions. The increased prevalence of ASIL seen among immunosuppressed HIV-seropositive men may be the result of both a non-specific increase in productive HPV infection and HIV-induced immune alterations of HPV-related neoplasia.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To determine whether at the time of HIV-1 seroconversion rapid progressors to AIDS and a low CD4 + count can be distinguished by the clinical presentation of primary HIV-1 infection and serological and immunological characteristics.Design: Prospective cohort study on HIV-1 infection in homosexual men.Setting: The Municipal Health Service, Amsterdam, The Netherlands.Subjects: One hundred and eight men who seroconverted for HIV-1 during follow-up.Main outcome measures: Progression to AIDS and progression to a CD4 + lymphocyte count < 200 × 106/I.Results: Symptomatic primary HIV infection with fever and skin rash, absence of anti-HIV core and transient HIV p24 antigenaemia were independent predictors of progression to AIDS at the time of HIV-1 seroconversion. A low CD4 + count immediately after seroconversion and the calendar year were independent predictors of progression to a low CD4 + count at the time of HIV-1 seroconversion.Conclusions: Even in the earliest stage of HIV-1 infection a small group of individuals at high risk for rapid progression to AIDS can be recognized by the clinical presentation of primary HIV infection, the presence of HIV p24 antigenaemia and the absence of a serological response to HIV core protein.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes ofPneumocystis cariniipneumonia (PCP) in HIV-infected patients.Design: An open randomized clinical trial.Patients and methods: HIV-infected patients (n = 331) with CD4 cell counts < 200 × 106/I or with AIDS but without a history of PCP or cerebral toxoplasmosis (CD were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment.Results: The mean follow-up was 313 days (range, 30–670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (Cl), 0.9–10.3], 3% (95% Cl, 0–6.3) and 8.3% (95% Cl, 2.8–13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P>0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P< 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P< 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies toToxoplasma gondii.Conclusions: Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences>15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective: This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX.Design: A prospective, open study.Setting: A tertiary referral hospital.Patient: Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX.Interventions: Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100mg, respectively, twice a week).Main outcome measures: That rechallenge is more likely to be successful in those with advanced HIV disease.Results: Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4 + cell count < 20 × 106/I than in those with a CD4 + cell count>20 × 106/I (31 versus 85%;P= 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred.Conclusions: Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4 + lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID