ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:HIV-2 is less pathogenic than HIV-1. In contrast to HIV-1, many isolates of HIV-2, including primary isolates, can infect cells independently of CD4.Objective:To compare the sensitivity of CD4-dependent and CD4-independent isolates of HIV-2 to antibody-mediated neutralization.Methods:The neutralization sensitivity of CD4-dependent and CD4-independent molecular clones of HIV-2 to a panel of HIV-2-positive serum samples was tested. Monoclonal antibodies to various epitopes across the viral envelope were used to determine whether a specific epitope conferred neutralization sensitivity. Neutralization sensitivity of primary isolates of HIV-2 able to infect in the absence of cellular CD4 was also investigated. Antibody binding to sensitive and resistant envelopes was analysed using enzyme-linked immunosorbent assay and flow cytometry.Results:CD4-independent ROD B was highly sensitive to neutralization by HIV-2-positive sera compared with the CD4-dependent isolate ROD A. Induction of ROD A to infect CD4-negative cells by soluble CD4 rendered it equally sensitive to antibody neutralization. Similarly, primary X4, R5 or dual-tropic isolates of HIV-2 were significantly more susceptible to neutralization when utilizing a CD4-independent route of infection. Neutralization sensitivity was not epitope specific but several conformation-dependent antibodies accentuated this phenotype. Antibody binding to monomeric or oligomeric envelope did not correlate with neutralization sensitivity.Conclusions:HIV-2 isolates utilizing a CD4-independent route of infection are more sensitive to antibody-mediated neutralization. Cellular CD4 may protect HIV-2 from neutralization. This sensitivity to neutralization may, in part, explain the lower virus load and slower progression to disease in HIV-2-infected individuals.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:The majority of infants infected through maternal transmission acquire the virus during birth or postpartum through breastfeeding: mucosal exposure is considered to be a major route of infection.Objectives:To develop passive immunization with human neutralizing monoclonal antibodies (mAbs) against mother-to-child transmission of HIV during delivery and through breastfeeding.Design:An oral challenge model in newborn rhesus macaques mimicked peri- and postpartum virus transmission.Methods:Neonatal rhesus macaques were challenged orally with the highly pathogenic, chimeric simian–human immunodeficiency virus SHIV89.6P and given post-exposure prophylaxis with a quadruple combination of neutralizing human mAbs, IgG1b12, 2G12, 2F5, and 4E10, directed against conserved epitopes of HIV envelope glycoproteins. Control animals were virus challenged but left untreated. All infants were followed prospectively for signs of viremia and immunodeficiency.Results:Two out of four macaque infants treated with neutralizing mAbs showed no evidence of infection; the other two maintained normal CD4 T cell counts. In contrast, all control animals became highly viremic and had profound CD4 T cell losses; three out of four died from AIDS within 1.5–6 weeks of the challenge.Conclusions:Passive immunization with this quadruple neutralizing mAbs combination may represent a promising approach to prevent peri- and postnatal HIV transmission. Furthermore, the epitopes recognized by the four neutralizing mAbs are key determinants to achieve complete protection and represent important targets against which to develop active, antibody-response-based AIDS vaccines.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To examine the prevalence of and risk for anal human papillomavirus (HPV) infection and abnormal anal cytology in sexually active adolescents.Design:Prevalence data from adolescents aged 13–18 years with and without HIV infection and with a history of high-risk sexual behavior.Methods:HPV DNA was detected using amplification techniques. Abnormal anal cytology was defined as atypical squamous cell of undetermined significance or worse.Results:Prevalence of anal HPV infection was similar in HIV-infected [28/58 (48%)] and uninfected [9/25 (36%)] boys (P= 0.3). but greater in HIV-infected [59/183 (59%)] than in uninfected [11/82 (13%)] girls (P< 0.001). Perianal warts were a risk for anal HPV in both boys [odds ratio (OR), 15.5; 95% confidence interval (CI), 1.6–149] and girls (OR, 9.9; 95% CI, 1.9–51.3). In subjects without anal warts, HIV infection was significant for girls (OR, 2.3; 95% CI, 1.1–4.9) and homosexual/bisexual orientation was significant for boys (OR, 5.2; 95% CI, 1.3–20.6). Abnormal anal cytology was more common among boys [32/77 (41.6%)] than girls [38/230 (16.5%)] (P< 0.001) and in addition to anal HPV, independent risk factors were positive HIV status in boys (OR, 6.5; 95% CI, 1.5–11.9) and number of partners within the past 3 months in girls (OR, 4.2; 95% CI, 1.5–11.9).Conclusions:Strong risk factors for abnormal anal cytology were HIV infection and anal HPV in boys and anal HPV and higher number of sexual partners for girls. The results suggest that anal cytology screening should be considered in HIV infected homosexual/bisexual males.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objectives:To evaluate once or twice daily vaginal exposure to 2 and 4% PRO 2000 Gel, a naphthalene sulfonate polymer microbicide, in sexually active HIV-uninfected women to determine the highest tolerated frequency and concentration combination, and to assess this in sexually abstinent HIV-infected women.Methods:Sixty three women from Providence, Philadelphia, Durban and Johannesburg were enrolled after being screened to exclude pre-existing illnesses and were instructed to use the product once or twice daily for 14 intermenstrual days. They underwent colposcopy prior to product use and after 14 days of product use, with a pelvic examination at day 7.Results:The product was well tolerated, with no serious adverse events, even though 73% of the participants had at least one adverse experience: 82% of these were classified as mild, and over 90% of the findings and symptoms were localized to the genital tract. Women who used the 4% gel twice daily tended to have more adverse events than all the other groups. Three participants did not complete the study; one because of Herpes simplex virus cervicitis, the second because of epithelial disruption, and the third because she became be pregnant. The remaining participants adhered to the study protocol and indicated that they would use the product if it were shown to be effective.Conclusions:PRO 2000 Gel was safe and well tolerated in sexually active HIV-uninfected and sexually abstinent HIV-infected women, enabling the product to be considered for evaluation in efficacy trials.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:Plasma viral load monitoring is an integral part of the standard of care for HIV-infected patients in industrialized countries. In developing countries, viral load assay is either unaffordable or hindered by on-site maintenance and/or technical problems.Objectives:To evaluate a new and simple quantitative assay for plasma HIV reverse transcriptase (RT) activity; and to compare RT activity-based and RNA-based quantification in plasma samples from patients infected by different subtypes of HIV-1 group-M, HIV-1 group-O and HIV-2.Methods:The RT-based viral load assay involves separation of the virion-protected RT and quantification of its activity with an enzyme immunoassay. Plasma viraemia was quantified both by RT activity and by RNA copies in 322 samples from 236 HIV-1 group M-infected patients, including serial samples from 54 patients. Samples from 49 patients infected by HIV-1 group O or HIV-2 were also tested.Results:RT activity and RNA copies were detected in 70% of plasma samples; respectively 25% and 1% of samples contained detectable RNA copies or RT activity alone. Measured RT activity corresponded to 48%, 96% and 100% of samples with 1.7–4.0 log10, 4.1–4.8 log10and 4.9–6.7 log10RNA copies/ml, respectively. The values of the two assays correlated independently of the HIV subtype (P< 0.0001) and group/type (P< 0.03). Patient follow-up showed a similar pattern of viraemia with the two assays.Conclusion:Plasma RT activity assay is a simple, cheap and reliable alternative for HIV viral load determination. As such, it could be particularly valuable for diagnosis and treatment monitoring in developing countries.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To investigate the correlation between genotypic studies performed on blood leukocytes and phenotypic results obtained from the corresponding blood viral isolates in AIDS patients with relapsing cytomegalovirus (CMV) retinitis.Methods:Sequential blood samples were collected from patients failing intravenous or oral ganciclovir therapy. The CMV UL97 gene was amplified directly from leukocyte DNA extracts for assessing the presence of viral mutations using restriction fragment length polymorphism analysis and direct sequencing. Positive viral cultures from the same blood samples were also analyzed for their susceptibility to ganciclovir and their UL97 genotype was determined.Results:Discordant CMV genotypes between the clinical specimen and the viral culture were found in at least one blood sample from three of the four patients with relapsing CMV retinitis. Furthermore, some UL97 mutations at known resistance codons (592, 594) were associated with a drug-susceptible phenotype. In all four cases, genotypic analyses of blood samples better correlated with clinical progression than phenotypic analyses of viral cultures.Conclusions:The presence of mixed viral populations in blood samples of AIDS patients and the potential selection bias introduced byin vitrosusceptibility testing may underestimate the real impact of CMV resistance in patients failing antiviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients.Methods:Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200–550 × 106cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 × 106IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74.Results:CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 × 106cells/l, respectively;P< 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P< 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P< 0.0001) and natural killer cells (P< 0.001). In a logistic regression analysis, odds of being responders to recall antigensin vitrowas 8.5-fold higher in IL-2 recipients (P= 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively;P= 0.01).Conclusions:The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To evaluate the population effectiveness of highly active antiretroviral therapy (HAART) in HIV progression and determine the heterogeneity of the effect of HAART in GEMES (Spanish multicenter study of seroconverters).Design:Multicenter cohort study.Methods:Data from 1091 persons with well-documented HIV seroconversion dates from 1980s to January 2000 were analysed. Risk of AIDS and death in subjects with same duration of HIV infection were compared in different calendar periods; before 1992, 1992–1995 (reference), 1996–1997, 1998 and 1999 with Kaplan–Meier methods and Cox proportional hazards models, allowing for late entry, fitting calendar period as time-dependent covariate and adjusting for transmission category, age and gender.Results:Statistically significant reductions in the risk of AIDS were first observed in 1998 [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.35–1.01] becoming more pronounced in 1999 (HR, 0.45; 95% CI, 0.24–0.84). Reduction in the risk of death was seen in 1997, though only reached borderline significance in 1999 (HR, 0.53; 95% CI, 0.26–1.07). Progression to AIDS and death was slower in women (HR, 0.68; 95% CI, 0.46–0.99 and HR, 0.53; 95% CI, 0.33–0.87, respectively). Compared with men who have sex with men (MSM), intravenous drug users (IDU) had lower reductions in the risk of AIDS and death.Conclusions:Reductions in incidence of AIDS and death in GEMES are seen after 1998 and 1999, respectively, compared with 1992–1995, being more pronounced in MSM compared with IDU, the commonest category in Spain.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:Among treated patients with drug-resistant viremia, structured treatment interruptions often result in the re-emergence of drug-susceptible HIV-1. Theoretically, this may allow for a more durable response to salvage therapy. We therefore studied the long-term treatment outcome to antiretroviral therapy in a cohort of patients who had previously interrupted therapy, focusing on the determinants of treatment success versus failure.Design:A prospective observational study of the response to antiretroviral therapy in patients resuming therapy after a treatment interruption. Virological and immunological studies were performed every month for 3 months and then every 3 months.Results:Twenty-four patients underwent a structured treatment interruption and resumed therapy after a variable period of time (median 20 weeks). The median duration of treatment after the treatment interruption was 109 weeks. A transient virological response was observed in all patients who resumed a regimen containing no drug to which their pre-interruption virus was fully susceptible. Virus isolated during virological failure was genotypically and phenotypically identical to the pre-interruption virus, exhibited reduced replicative capacity, and replicatedin vivoat levels similar to the pre-interruption baseline. In contrast, durable viral suppression (< 200 copies/ml) was observed in patients who initiated a regimen containing only one drug to which their pre-interruption virus was fully susceptible. Despite viral suppression, the pre-interruption drug-resistant virus population remained detectable in two patients.Conclusion:Although drug-resistant HIV-1 persists at low levels during and after the interruption of therapy, durable suppression of this virus population may be achieved with a combination regimen containing only one fully active agent.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID