摘要:

Objective:To describe two cases of cryptococcal meningitis and one re-exacerbation ofCryptococcus-associated meningitis occurring in temporal association with commencement of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection (CD4 cells < 50 × 106/l), which suggests that partial immune restitution can facilitate development of clinically apparent meningitis in response toCryptococcusor its antigen.Design:All HIV-infected patients with culture-proven cryptococcal meningitis diagnosed at a tertiary referral centre specialist infectious diseases unit from 1 January 1996 to 31 December 1996 were reviewed to examine the clinical and immunological parameters prior to and after commencing antiretroviral therapy.Results:Three patients were diagnosed with clinically apparent meningitis within 7–39 days of changing or altering antiretroviral combination therapy consisting of zidovudine or stavudine, in combination with lamivudine and saquinavir. All patients had CD4 cell counts below 50 × 106/l at initiation of therapy. Following institution of HAART, evidence of immune restitution was suggested by the following: (i) significant increases (3.7–14-fold) in numbers of CD4 cells (all three patients), (ii) significantly reduced (> 2–4 log10reduction) HIV viral loads (two out of three patients), and (iii) prominent inflammatory changes in cerebrospinal fluid (white blood cells > 10 × 106/l) at diagnosis (two out of three patients).Conclusions:Our report suggests that in patients with advanced HIV infection, partial immune restitution induced by HAART can precipitate onset of clinically apparent meningitis in those patients with latent cryptococcal central nervous system infection or with residual cryptococcal antigen present in the cerebrospinal fluid.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:The aim of treatment for HIV disease is prolonging survival and improvement in health-related quality of life. Ritonavir is a potent, orally bioavailable HIV protease inhibitor with demonstrated impact on surrogate endpoints, AIDS-defining disease, and mortality.Objectives:To evaluate the effect of ritonavir combined with reverse transcriptase inhibitor therapy on patient functioning and well-being.Methods:An international, multicenter randomized placebo-controlled clinical trial of ritonavir was conducted in HIV-infected patients with CD4 cell counts ≤ 100 × 106/l. A total of 1090 patients were randomized to ritonavir and continued treatment with as many as two nucleoside agents (n = 543) or placebo and continued treatment with as many as two nucleoside agents (n = 547). Health-related quality of life was measured at baseline and after 3 and 6 months of treatment using the Medical Outcomes Study HIV Health Survey (MOS-HIV) and HIV-related symptoms scale. MOS-HIV contains 10 subscales and two summary scores (physical health and mental health).Results:The two treatment groups were comparable on baseline CD4 cell counts, demographic characteristics, and MOS-HIV and HIV symptom subscale scores. After 3 months, statistically significant differences (P< 0.03) favoring the ritonavir-treated patients were seen on the physical health summary, mental health summary, and general health perceptions, social function, mental health, and energy/fatigue subscales. After 6 months of ritonavir therapy, significant differences were observed on physical health and mental health summary scores (P< 0.001), and on measures of general health perceptions, physical function, role function, social function, cognitive function, mental health, health distress, energy/fatigue, and overall ratings of quality of life (P< 0.01). Ritonavir-treated patients reported fewer fever symptoms and neurologic symptoms than the placebo group after 6 months of treatment (P≤ 0.005).Conclusions:Ritonavir therapy, combined with other antiretroviral treatments, significantly contributes to maintenance of functioning and well-being over at least 6 months in patients with advanced HIV disease.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:Practice guidelines recommendingMycobacterium aviumcomplex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors.Objective:To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors.Design:Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin.Main outcome measures:Survival, quality of life, quality–adjusted survival, health care costs and marginal cost-effectiveness ratios.Results:Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233 000 to $239 800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44 300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41 500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54 300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 × 106cells/l per year, or the CD4 count was greater than 50 × 106cells/l.Conclusion:MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 × 106cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To compare the antiretroviral effect and safety of zidovudine (ZDV)–lamivudine (3TC) with that of stavudine (d4T)–3TC.Methods:In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts ≥ 200 × 106/l and plasma HIV RNA load ≥ 10 000 copies/ml were randomized to receive ZDV–3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T–3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported.Results:Forty-seven patients were treated (24 took ZDV–3TC; 23 took d4T–3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log10copies/ml (ZDV–3TC,P< 0.0001) and from 4.98 to 3.03 log10copies/ml (d4T–3TC,P< 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV–3TC and in 10 out of 22 patients with d4T–3TC. Median virus load at week 24 was 2.41 log10and 2.29 log10copies/ml (P= 0.14), respectively. Seventy-five per cent (15 out of 20; ZDV–3TC) and 95% (18 out of 19; d4T–3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV–3TC and 12/12 d4T–3TC). At week 12, CD4 cell counts had increased with a median of 110 × 106/l in the ZDV–3TC group (baseline, 315 × 106/l) and a median of 115 × 106/l in the d4T–3TC groupo (baseline 290 × 106/l). At week 24, the median increases were 90 and 120 × 106/l, respectively. Overall the increase of CD4+ cells was higher in the d4T–3TC group (P= 0.02).Conclusion:d4T–3TC is at least as effective as ZDV–3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T–3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To examine the effect of treatment with an inactivated, gp120-depleted, HIV-1 immunogen (Remune) in 30 Thai subjects infected with HIV-1 subtype E.Design:Sixty-week open-label study.Methods:Thirty HIV-positive volunteers with CD4 cell counts ≥ 300 × 106/l were given intramuscular injections of Remune into the triceps muscle on day 1 and then at weeks 4, 8, 12, 24, 36, 48 and 60.Results:Treatment with Remune was well-tolerated and augmented HIV-1-specific immune responses. Furthermore, subjects had a significant increase in CD4 cell count (P< 0.0001), CD4 cell percentage (P< 0.0001), CD8 cell percentage (P< 0.0001), and body weight (P< 0.0001) compared with pretreatment levels. Fourteen subjects with detectable viral load at day 1 showed a decrease at week 60 (P= 0.04). Retrospective Western blot analysis showed 23 subjects with increased intensity of antibody bands and 15 patients showed development of new reactivities to HIV proteins, especially towards p17 and p15.Conclusion:These results indicate that HIV-specific immune-based therapeutic approaches such as Remune should be further examined in countries with different clades of HIV-1 and where access to antiviral drug therapies is limited.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To prospectively study changes in the social networks of persons at presumably high risk for HIV in a community with low prevalence and little endogenous transmission.Methods:From a cohort of 595 persons at high risk (prostitutes, injecting drug users, and sexual partners of these persons) and nearly 6000 identified contacts, we examined the social networks of a subset of 96 persons who were interviewed once per year for 3 years. We assessed their network configuration, network stability, and changes in risk configuration and risk behavior using epidemiologic and social network analysis, and visualization techniques.Results:Some significant decrease in personal risk-taking was documented during the course of the study, particularly with regard to needle-sharing. The size and number of connected components (groups that are completely connected) declined. Microstructures (small subgroups of persons that interact intensely) were either not present, or declined appreciably during the period of observation.Conclusions:In this area of low prevalence, the lack of endogenous transmission of HIV may be related in part to the lack of a network structure that fosters active propagation, despite the continued presence of risky behaviors. Although the relative contribution of network structure and personal behavior cannot be ascertained from these data, the study suggests an important role for network configuration in the transmission dynamics of HIV.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To estimate the incubation-period distribution (time from seroconversion to AIDS) accounting for death before an AIDS diagnosis (DBAD) in a cohort of injecting drug users (IDU) in Amsterdam, The Netherlands and to compare these estimates with those previously obtained from a contemporaneous study of homosexual and bisexual men in Amsterdam carried out using the same facilities.Design:Participants in a cohort study begun in Amsterdam at the end of 1985 have scheduled follow-up visits every 4 months. All participants of Dutch nationality and who had two or more follow-up visits before January 1996 from which CD4 measurements were available were included in this study. Data concerning AIDS diagnosis and death were verified through review of national and municipal registries.Methods:Because time of seroconversion was unknown for study participants and because IDU are at substantial risk for DBAD, we used a Markov model with CD4-based stages that allows for DBAD. The parameters in this model were estimated using the method of maximum likelihood and confidence intervals were calculated using bootstrap methods.Results:A total of 173 IDU (134 seroprevalent, 39 seroincident) made 1829 visits. Nearly 10% of the visits were non-consecutive. Forty-five IDU developed AIDS and 25 died without an AIDS diagnosis. We estimated that 24% [95% confidence interval (CI), 17–25%] of IDU die before an AIDS diagnosis. As a result, the median time from seroconversion to AIDS (10.5 years; 95% CI, 9.1–10.7 years) is considerably longer than the median time from seroconversion to death (8.3 years; 95% CI, 7.9–8.5 years). Conditional on survival to an AIDS diagnosis, the median time to AIDS is 8.2 years (95% CI, 7.7–8.7 years). The median survival time after a diagnosis of AIDS is estimated to be 1.0 years.Conclusion:The high occurrence of DBAD in IDU has a considerable influence on estimates of the incubation-period distribution. Progression from seroconversion to death was faster in the IDU cohort than in a cohort of homosexual men in Amsterdam (median, 8.3 years and 9.6 years, respectively). However, progression to AIDS conditional on survival to an AIDS diagnosis seems to be similar in both the IDU cohort and in the cohort of homosexual men (median, 8.2 years and 8.3 years, respectively).

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection.Methods:Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors.Results:Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22–56] at < 7 days, 56 out of 58 (97%; 95% CI, 88–100) at 7–41 days, and 37 out of 39 (95%; 95% CI, 83–99) at 42–93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97–100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92;P= 0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%;P= 0.05).Conclusions:The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID