摘要:

Objectives:To investigate the factors related to viral load becoming undetectable among patients from Southern Alberta who started a protease inhibitor for the first time, and to determine the factors related to subsequent re-emergence of detectable viral load amongst those patients whose viral load initially became undetectable.Subjects and methods:A total of 243 patients from the Southern Alberta Clinic had started a protease inhibitor for the first time and had been followed up for a median time of 32 weeks. Standard survival techniques including Kaplan-Meier techniques and Cox proportional hazards models were used to determine which factors were related to viral load becoming undetectable.Results:At 24 weeks after first exposure to a protease inhibitor, 52.8% of the patients [95% confidence interval (CI), 45.2–56.6] had achieved an undetectable viral load. In a multivariate analysis, those with a higher initial viral load were less likely to become undetectable [relative hazard (RH), 0.50; 95% CI, 0.35–0.70;P< 0.0001], whereas those starting more new drugs (RH per new drug, 1.54; 95% CI, 1.01–2.11;P= 0.048) were significantly more likely to achieve an undetectable viral load. Amongst 111 patients whose viral load became undetectable, Kaplan-Meier analysis indicated that 15.5% of patients experienced re-emergence of detectable viral load at 24 weeks after the first undetectable viral load. A higher CD4 cell count was associated with a lower risk of viral load becoming detectable (RH, 0.73; 95% CI, 0.53–1.00;P= 0.049), as was treatment with indinavir (versus any other protease inhibitor RH, 0.17; 95% CI, 0.03–0.86;P= 0.033).Conclusions:A significant proportion of patients in a routine clinic setting achieved an undetectable viral load measurement after first starting a protease inhibitor; viral load in patients with a higher CD4 cell count was more likely to become and stay undetectable. There was no evidence that patients who were drug-naive experienced significantly worse virological effects than drug-experienced patients, as long as the same number of new drugs was started at the date of first exposure to a protease inhibitor. Further follow-up of these patients is warranted to study the longer term effects of treatment with protease inhibitors.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To assess the efficacy and safety of all-trans-retinoic acid (ATRA), a retinoid with antitumour activity that inhibitsin vitrothe growth of Kaposi's sarcoma cells, in patients with low-risk AIDS-associated Kaposi's sarcoma.Design:Non-randomized phase II study, using a group sequential procedure to determine whether the response rate to ATRA was above 10%.Setting:Nine referral French centres.Patients:Twenty HIV-seropositive men with CD4 cells ≥ 200 × 106/l, low-risk Kaposi's sarcoma [T0I0S0according to the classification of AIDS Clinical Trials Group (ACTG)] not previously treated with systemic anti-Kaposi's sarcoma agents, and with at least four measurable lesions were included.Interventions:ATRA was given orally 45 mg/m2daily for 12 weeks.Main outcome measure:Tumour response evaluated according to ACTG criteria.Results:Nineteen patients were evaluated for response: partial response, stabilization and progression were found in eight (42%), seven (37%), and four (21%) patients, respectively. Gradual flattening and lightening of lesions was observed in responders after at least 2 months of ATRA. All patients with partial response at week 12 pursued ATRA for another 15 ± 7 weeks. Further improvement was observed in six patients. Median duration of response was 332 days. Cheilitis, transient headaches and skin dryness were the main toxicities noted. No significant changes in HIV viral burden or serum interleukin-6 pathways were observed.Conclusions:ATRA is well tolerated and effective enough in Kaposi's sarcoma patients to warrant further evaluation. © 1998 Lippincott Williams & Wilkins

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To determine the impact of HIV infection onStreptococcus pneumoniaebacteraemia in adults and children by analysing the prevalence and clinical features of such diseases and determining the prevalent serotypes/serogroups and susceptibility patterns of isolates.Design:Patients were identified prospectively from January to October 1996.Setting:Chris Hani Baragwanath Hospital, Soweto, a tertiary referral hospital treating adults and children, in an urban district near Johannesburg, South Africa.Patients and methods:All patients withS. pneumoniaeisolated from blood culture by the Microbiology Department, Chris Hani Baragwanath Hospital were studied. Clinical and microbiological features were recorded.Results:A total of 178 patients withS. pneumoniaewere investigated as part of the study; 49 were aged < 13 years. HIV seroinfection was present in 25 (51%) children and 58 (45%) adults. The incidence ofS. pneumoniaebacteraemia was 36.9-fold increased in HIV-seropositive children and 8.2-fold increased in HIV-seropositive adults compared with HIV-seronegative individuals. Both adult and paediatric HIV-seropositive patients withS. pneumoniaebacteraemia were significantly younger than HIV-seronegative patients. Pneumonia was a significantly more common presentation in HIV-seropositive children, otherwise the spectrum of disease and outcome were similar in HIV-seronegative and positive groups. Serotype 1S. pneumoniaeisolates were significantly less common in HIV-infected individuals (both adults and children). Resistance to penicillin was increased inS. pneumoniaeisolates from HIV-infected patients (significant in adults). Patients with penicillin-resistant isolates did not have a poorer outcome. The potential coverage of serotypes/serogroups included in the proposed nine-valent conjugate pneumococcal vaccine was 88% in HIV-seronegative children and 83% in HIV-seropositive children. The potential coverage of the currently available 23-valent pneumococcal vaccine for adults was 98.2 and 100% for HIV-infected and HIV-uninfected adults, respectively.Conclusion:The burden of bacteraemia due toS. pneumoniaein HIV-seropositive individuals admitted to our hospital is considerable. Differences in theS. pneumoniaeserotypes/serogroups in HIV-infected patients have been demonstrated with resultant differences in antibiotic susceptibility patterns. Excellent potential for vaccine coverage was demonstrated for both HIV-seronegative and HIV-seropositive individuals. Further studies are necessary to test the clinical efficacy of pneumococcal vaccination of HIV-seropositive adults and children as a potential preventative measure against this prevalent disease.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To assess the potential discrepancies in reported changes in plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomized controlled clinical trial.Design:Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and nevirapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initially. All PVL values less than 500 copies/ml were retested with a more sensitive assay with a lower quantification limit of 20 copies/ml.Methods:Several summary measures for assessing change in PVL were calculated using three different methods to adjust for PVL values less than the quantification limit of the assay. The differences between these measures were evaluated.Results:We found that the magnitude of the discrepancy between summary measures used to report changes in PVL depended on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data analysis, and the relative difference between the quantification limits of the conventional and more sensitive assay.Conclusion:The lack of consensus in reporting of PVL data in the literature makes the interpretation of published trial results difficult. In the absence of agreement on the most appropriate summary measure of PVL data, we recommend that all summaries include information on the quantification limit of the assay used, the proportion of observations at or below the quantification limit and how these observations were handled in the data analysis.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:The efficacy of highly active antiretroviral treatment (HAART) in HIV-1 disease may vary between nucleoside-naive and experienced patients as well as between patients with different viral phenotypes and in different stages of disease.Objective:To investigate variables of importance for successful long-term viral suppression by analysing virological, clinical and immunological characteristics at initiation of protease inhibitor treatment on suppression of HIV RNA over 1 year.Design:An open, non-randomized, observational clinical study.Setting:Venhälsan, Department of Dermatovenereology, Söder Hospital, Stockholm, Sweden.Patients:A total of 147 unselected advanced patients with known HIV-1 infection for a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996.Interventions:All patients received HAART with at least two nucleoside analogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analogues for a mean of 39 months.Measurements:CD4+ lymphocyte count, plasma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at baseline. Viral load and CD4+ lymphocyte count were determined every 3 months.Results:Patients were analysed on an intention-to-treat basis. The mean CD4+ lymphocyte count at baseline was 170 × 106/l and the median viral load was 68 600 copies/ml. Heterozygosity for the Δ32 deletion of theCCR-5gene (Δ32/wt) was found in 27%. MT-2 positive virus (syncytium-inducing) was isolated in 46%. Logistic regression revealed that nucleoside analogue experience and baseline log10HIV-1 RNA were the only factors independently related to plasma HIV-1 RNA levels below 500 copies/ml after 1 year of treatment, which was found in 69%.Conclusion:The virological outcome after 1 year of HAART was strongly correlated to prior treatment history and baseline viral load, whereas CD4+ lymphocyte count,CCR-5genotype and viral biological phenotype had less influence. The long-term antiviral efficacy of HAART was lowest in individuals with previous nucleoside analogue treatment and a high baseline viral load. In these individuals an even more aggressive treatment should be considered. © 1998 Lippincott Williams & Wilkins

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world.Methods:For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars.Results:The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined.Conclusion:Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To examine the implications of variation in maternal infectivity on the timing of mother-to-child HIV transmission through breastfeeding.Design and methods:A mathematical model of mother-to-child HIV transmission was developed that incorporates two main features: (i) the fetus/child potentially experiences a series of exposures (in utero, intrapartum, and via breastmilk) to HIV; and (ii) variation in maternal infectivity. The model was estimated from different sources of epidemiological data: a retrospective cohort study of children born to HIV-1-infected women in Sao Paulo State, Brazil, the International Registry of HIV-Exposed Twins, and the AIDS Clinical Trials Group 076 trial, which assessed the effectiveness of zidovudine in preventing mother-to-child HIV transmission.Results:Variation in maternal infectivity results in higher average risk of breastfeeding-related transmission in the early stages of breastfeeding than in the late stages, even in the absence of a direct relationship between transmission risk and the age of the child. However, the available data were unable to resolve the quantitative importance of this mechanism.Conclusions:Our model has helped identify a previously unrecognized determinant of the timing of breastfeeding-related HIV transmission, which may have adverse implications for the effectiveness of certain interventions to reduce mother-to-child HIV transmission such as maternal antiretroviral therapy in breastfeeding populations and the early cessation of breastfeeding.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To accurately measure AIDS-related mortality relative to other causes and its impact on life expectancy in Brazzaville, Congo.Design:Investigation of all deaths during a 1-month period in Brazzaville.Methods:From 10 July to 9 August 1996, all bodies handled by Brazzaville's three morgues were examined by a physician. Relatives were interviewed on the circumstances of death, while additional clinical data were gathered from hospital files. Blood samples were systematically drawn from the bodies in two of the three morgues and tested for HIV antibodies.Results:Amongst the 756 bodies examined at the three morgues, 149 (19.7%) AIDS cases were identified. HIV-1 prevalence was 26.2% (38 out of 145) amongst the subjects in the two morgues where HIV serology was systematically performed. AIDS was the leading cause of death in adults (age ≥ 15 years), with 25.1% (122 out of 487) of the adults diagnosed with AIDS. The proportion of adult female AIDS cases was significantly higher than the proportion of male cases (30.2 versus 21.0%;P< 0.05). Moreover, female AIDS cases were significantly younger than male cases (median age, 32 versus 42 years;P< 0.00001). Overall AIDS mortality rate amongst adults was 2.8 per 1000 for men and 3.2 per 1000 for women. The impact of AIDS on life expectancy at birth is 4.3 years for women and 3.3 years for men.Conclusion:Our study provides a direct measure of AIDS contribution to mortality relative to other causes, using a rapid, low cost, reliable and replicable method. Clearly, the impact of AIDS is strongest on female life expectancy.

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