摘要:

ObjectiveTo examine changes in sexual activity and unprotected sexual intercourse among HIV-infected patients before and after the initiation of protease inhibitor therapy.DesignAn analysis of data from the SEROCO Study, a French prospective cohort.MethodsAll 191 patients who initiated protease inhibitor therapy after 1 January 1996, who were interviewed within one year before the initiation of therapy (Time 1), and who had at least 6 months of follow-up after therapy initiation (Time 2) were included. Patients provided information about sex partner characteristics and unprotected sexual intercourse.ResultsEighty-one (42%) were gay or bisexual men, 46 (24%) were heterosexual men, and 64 (34%) were women. No significant increases were found in either the number of patients reporting anal or vaginal sex or the number reporting unprotected sexual intercourse after protease inhibitor initiation. However, in matched pair analysis, gay or bisexual men were three times more likely to report having had unprotected sexual intercourse with partners who were of HIV-negative or unknown serostatus after protease inhibitor initiation [relative risk (RR) = 3.0, 95% confidence interval (CI) = 1.2–7.6]. Non-significant decreases in unprotected sexual intercourse among both heterosexual men and women were also observed. No relationship between plasma viral load after protease inhibitor initiation and unprotected sexual intercourse was found in these data.ConclusionsA relapse in sex risk practices among some HIV-infected gay or bisexual men cannot be ruled out and requires both continued monitoring and immediate secondary preventative intervention.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background90 K is a secreted human serum glycoprotein with immune modulatory activity.MethodsSerum 90 K levels were determined by an enzyme-linked immunosorbent assay in 19 HIV-1-infected mothers at the time of delivery, in their new-borns (11 HIV-1 infected and eight uninfected), in 26 HIV-1-uninfected mothers and in 86 new-borns of HIV-1-uninfected mothers.Results90 K levels in HIV-1-infected transmissive mothers (22.4 ± 13.9 μg/ml) were similar to those of HIV-1-uninfected mothers (21.1 ± 7.6 μg/ml;P= 0.715), but lower than those of HIV-1-infected non-transmissive mothers (45.5 ± 24.8 μg/ml;P= 0.019). The levels were higher in HIV-1-uninfected (47.6 ± 22.4 mg/ml) than HIV-1-infected (23.7 ± 15.6 μg/ml;P= 0.014) new-borns of HIV-1-infected mothers. The new-borns of HIV-1-uninfected mothers had lower levels (11.7 ± 5.3 μg/ml) than both HIV-1-infected and HIV-1-uninfected new-borns of HIV-1-infected mothers (all differences,P< 0.001).ConclusionThese results suggest that high 90 K protein serum levels in HIV-1-infected mothers and their new-borns are associated with lack of mother-to-child HIV-1 transmission.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo describe awareness and use of antiretroviral treatments, viral load monitoring, and post-exposure prevention; to assess changing concerns about HIV transmission; and to examine the effect of these advances on sexual behavior in HIV-serodiscordant heterosexual couples.MethodsCross-sectional analysis of a baseline sample of 104 couples (n = 208 individuals) from the California Partners Study II, an intervention trial for HIV-serodiscordant couples in California. Questions on sexual practices, viral load testing, HIV treatment, post-exposure prevention, and their effect on sexual behaviors, risk taking and transmission concerns were measured at intake.ResultsOver two-thirds of couple members surveyed reported unprotected sex with their partner in the past 6 months. Among seropositive respondents, 37% were taking protease inhibitor therapy, 92% had undergone viral load testing, and of those, 40% said it had ben undetectable at their most recent test. Most respondents, regardless of serostatus, said that viral load testing and awareness of post-exposure prevention had no effect on their condom use. In addition, perceiving that their partner had an undetectable viral load was associated with having protected sex among seronegative subjects (P< 0.05). Seropositive respondent taking protease inhibitors were 2.4 times less likely to report unprotected sex compared with those not taking protease inhibitors (P= 0.05). However, up to 33% of seropositive and 40% of seronegative respondents acknowledged decreased transmission concerns in the light of the new HIV treatments. In comparison with their seropositive partners, seronegative individuals were more likely to acknowledge increased risk taking and decreased HIV transmission concerns (P< 0.05).ConclusionsNew medical advances were not associated with unprotected sex in HIV-serodiscordant couples. However, new treatment options may decrease concerns about HIV transmission, particularly among seronegative partners. Providers should discuss the effect of antiretroviral treatments on sexual transmission risk with their patients. The inclusion of seronegative partners in counseling interventions may decrease risk taking in serodiscordant couples.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundAntibody responses to immunization are often compromised in patients infected by HIV-1, and the use of childhood immunization in affected children is controversial. We investigated whether multiple immunizations with a T cell-dependent neoantigen, bacteriophage ΦX174, induce selective immune attrition and post-vaccination viremia.MethodsSeventeen asymptomatic, antiretroviral therapy-naïve HIV-1-infected patients with a CD4 cell count of 450 cells/μl or greater were immunized in 1990/1991 with three intravenous doses of bacteriophage ΦX174. Group 1 received zidovudine (ZDV) during the primary and secondary immunization. Group 2 received ZDV exclusively during the tertiary immunization. Bacteriophage-specific antibodies of the IgM and IgG class, lymphocyte phenotypes (CD4+, CD8+, CD4+DR+, CD8+DR+, CD4+CD45RO+ and CD4+45RA+, CD4+CD45RO+DR+) and HIV-1 plasma viremia were measured sequentially.ResultsIn both patient groups the primary, secondary and tertiary antibody responses, as expressed by geometric mean antibody titres and IgM to IgG switch, were impaired. Booster immunizations resulted in a progressive attrition of specific antibody responses to bacteriophage. Antibodies to tetanus toxoid remained stable. The HIV-1 viral loads, which were evaluated in archived specimens from eight patients, increased after immunization but returned to baseline appoximately 4 weeks later. The humoral immune attrition and increases in plasma viremia were blunted by concomitant short courses of ZDV.DiscussionMultiple boosters of immunizations in asymptomatic treatment-naive HIV-1-infected patients may result in a specific immune attrition and vaccine-induced viremia. Short-term monotherapy with ZDV may have blunted these adverse effects. Hyperimmunization of HIV-1-infected patients may be detrimental unless accompanied by antiretroviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThe use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time.MethodsWe performed a cross-sectional analysis of whole-body, lumbar spine (L1–L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry.ResultsMen receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13–4.23) (P= 0.02). Subjects receiving protease inhibitors had greater central : appendicular adipose tissue ratios than the other two groups (P< 0.0001). There was no relationship between the central : appendicular fat ratio and the lumbar spine or proximal femur bone mineral densityt- orz- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART.ConclusionsOsteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death.DesignRetrospective analysis of HIV-2 cohort subjects.MethodsFifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used.ResultsThe mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10RNA copies/ml [95% confidence interval (CI), 0.81–2.7;P =0.0006;r= 0.46; n = 52] and 1.76 CD4% faster for every increase in log10DNA copies/105PBMC (95% CI 0.46–3.1;P =0.01;r= 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P =0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10increase in RNA load (95% CI, 1.3–3.5;P =0.0023) but only by 1.09 for each log10increase in DNA load (95% CI, 0.64–1.87;P =0.8).ConclusionThis longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo analyze the role of CD95/CD95 ligand (CD95L) expression and functionality in peripheral blood lymphocytes (PBL) during primary, acute HIV syndrome (AHS) and in the subsequent period.PatientsTwelve patients were studied during the acute phase of the viral infection and most were followed for some months.MethodsCell culture and cytotoxicity assays based upon51Cr release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow cytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELISA) for the determination of soluble CD95 and CD95L plasma levels, quantitative competitive (QC) reverse transcription polymerase chain reaction (RT-PCR) with an original RNA competitor for the analysis of CD95L mRNA expression and QC RT-PCR for determining plasma viral load.ResultsThe analysis of PBL during this phase revealed that almost all cells, including CD8 T cells with a virgin phenotype, B lymphocytes and natural killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal antibodies or binding to CD95L induced rapid apoptosis. However, CD95L mRNA was not expressed in PBL from these patients and was poorly inducible. Soluble CD95 was found in the plasma of all patients, but only in a few at high levels, even some months after seroconversion. In contrast, soluble CD95L was detected in only one patient, this occurring after the symptomatic period. For 10 of the 12 patients, expression of CD95 on the cell membrane or in the plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not altered by decreased lymphocyte activation or by efficient antiretroviral therapy.ConclusionsIn patients experiencing an acute, primary HIV infection, a prolonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogenesis of the disease. The hypothesis can be put forward that a complex balance exists between proapoptotic events (increase in CD95 expression), probably triggered by the host as a method to limit viral production, and antiapoptotic events (decrease in CD95L expression) probably triggered by the virus as a way to increase its production and survival.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy.Design and settingA cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels.ParticipantsThirty-four HIV-infected people with a median of 12 months of PI therapy.Main outcomesAdherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance.ResultsMedian adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36–65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P< 0.03).ConclusionA substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo investigate the effect of combination antiretroviral therapy on plasma HIV-1 RNA as measured by HIV RNA PCR and to assess their safety and tolerability.DesignA randomized, multicentre, double-blind, placebo-controlled trial.SettingMulticentre study in eight European countries, Australia and Canada.PatientsAntiretroviral naive patients (n = 103) with CD4 cell counts between 150 and 500 × 106/l.InterventionPatients were randomly assigned to zidovudine (ZDV; 200 mg three times per day) plus lamivudine (3TC; 150 mg twice per day) or to ZDV + 3TC + indinavir (IND; 800 mg q8h) for 52 weeks.Main outcome measuresDegree and duration of reduction of plasma HIV-1 RNA as measured by RNA PCR; Development of drug-related toxicities sufficiently severe to warrant dose modification, interruption or permanent discontinuation.ResultsZDV + 3TC + IND reduced plasma HIV-1 RNA (P< 0.001) and increased CD4 cell count significantly (P =0.01) more than ZDV + 3TC. The addition of IND to ZDV + 3TC as initial therapy markedly increased the proportion of patients with plasma HIV-1 RNA values < 500 copies/ml (31/52, 60%) or 20 copies/ml (24/52, 46%) as compared with ZDV + 3TC (9/50, 18% or 2/50, 4% respectively) at week 52 in an intention-to-treat, missing = failure analysis. Assessment of time to virological rebound (> 0.5 log10copies/ml above nadir) showed that patients who attained a minimum plasma HIV-1 RNA of ⩽ 20 copies/ml were less likely to rebound than those who did not reach this threshold. The addition of IND to ZDV + 3TC did not result in any significant increase in adverse experiences.ConclusionZDV + 3TC + IND resulted in a considerable improvement compared with the double combination, in reduction in plasma HIV-1 RNA, increase in CD4 cell count and proportion of patients with HIV RNA below the limit of detection. Despite an average 3 log10decrease in plasma HIV-1 RNA on triple therapy, however, maximal suppression (⩽ 20 copies/ml) was only attained in about one-half of the patients in an intent-to-treat analysis.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo compare the clinical features and T-cell subsets among 160 patients with acute HIV-1 infection not treated with antiretroviral agents from three different locations (Geneva, Seattle and Sydney).DesignPatients with documented acute HIV-1 infection were enrolled in four prospective studies: one randomized placebo controlled trial (RCT) and three observational cohort studies.SettingAll patients were diagnosed and followed in three university affiliated tertiary clinical care centers.MethodsThe chi-square test was used for comparing proportions and one way analysis of variance (ANOVA) for comparing continuous variables among these groups. Multiple regression analysis was used to identify the variables independently associated with the duration of acute HIV-1 infection. The differences in mean CD4 and CD8 load between centers were assessed using the random-effect models for the longitudinal data.ResultsMinor differences were noted in the frequency of symptoms among subjects enrolled at different locations. RCT patients reported a longer duration of symptoms (31 days) compared with that for observational patients (15 days;P< 0.0001). For the most common symptoms such as fever, skin rash, arthralgia, myalgia, and headaches, a longer duration was observed in the RCT group compared with that for observational patients (Prange, 0.001 to < 0.0001). T-cells subsets within 100 days of seroconversion did not statistically differ by centre or by mode of recruitment.ConclusionsThese results suggest a selection bias toward patients with longer symptomatic acute HIV-1 infection enrolled in the RCT. Data collected from RCT are not comparable to that collected in observational studies. However, data from collaborative international studies can be combined.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID