A Mocroft

Decline in the AIDS and death rates in the EuroSIDA study: an observational study

BACKGROUNDnSince the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible changes in these rates across Europe.nnnMETHODSnWe analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6-monthly periods and in three treatment eras (pre-HAART, 1994-1995; early-HAART, 1996-1997; and late-HAART, 1998-2002).nnnFINDINGSnThe incidence of AIDS or death fell after September, 1998, by 8% per 6-month period (rate ratio 0.92, 95% CI 0.88-0.95, p<0.0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/microL or less (0.43, 0.35-0.53, p<0.0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0.0001). In multivariate Coxs models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1.39; 95% CI 1.16-1.67, p=0.0004) and all deaths (1.29; 1.08-1.56, p=0.0065) in the pre-HAART era, and a reduced risk of AIDS (0.62; 0.50-0.77, p<0.0001) and all deaths (0.66; 0.53-0.82, p=0.0002) in the late-HAART era.nnnINTERPRETATIONnThe initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study.

ObjectivesThe causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths. MethodsAnalyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients. Incidence rates of pre-AIDS deaths were compared to overall rates. Factors relating to pre-AIDS deaths were identified using Cox regression. ResultsDeath rates declined from 15.6 to 2.7 per 100 person-years of follow-up (PYFU) between 1994 and 2001. Pre-AIDS incidence declined from 2.4 to 1.1 per 100 PYFU. The ratio of overall to pre-AIDS deaths peaked in 1996 at 8.4 and dropped to < 3 after 1998. The adjusted odds of dying following one AIDS defining event (ADE) increased yearly (odds ratio, 1.53;P < 0.001), conversely the odds of dying following three or more ADE decreased yearly (odds ratio, 0.79;P < 0.001). The proportion of deaths that followed an HIV-related disease decreased by 23% annually; in contrast there was a 32% yearly increase in the proportion of deaths due to known causes other than HIV-related or suicides. Injecting drug users (IDU) were significantly more likely to die before an ADE than homosexuals (relative hazard, 2.97;P < 0.0001) and patients from northern/eastern Europe (relative hazard, 2.01;P < 0.0001) were more likely to die pre-AIDS than southern patients. ConclusionsThe proportion of pre-AIDS deaths increased from 1994 to 2001; however, the incidence of pre-AIDS deaths and deaths overall declined. IDU and subjects from northern/eastern Europe had an increased risk of pre-AIDS death. HIV-positive patients live longer therefore it is essential to continue to monitor all causes of mortality to identify changes.

CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients.

We investigated the relationship between three prognostic markers, CD4 lymphocyte count, serum beta2-microglobulin (beta2M) levels, and CD8+,CD38+ lymphocyte percent, and the association with the rate of development of AIDS. The markers were measured regularly throughout follow-up in 224 patients. The risk of developing AIDS during follow-up was investigated using Cox proportional hazards models. Time-updated values of the prognostic markers were used, which modelled the risk of AIDS according to the latest measurement of the marker rather than using a single value of the marker at baseline. During a median follow-up period of 13.6 months (range 0.5-31.9 months), 34 cases of AIDS occurred. In a univariate analysis, all three markers predicted the development of AIDS; a 10% increase in the percentage of CD8+ T cells expressing CD38+ resulted in an 88% increase in the risk of AIDS (95% confidence interval: 53-130%; p < 0.0001). After adjustment for the current CD4 count and beta2M, a 10% increase in the CD8+,CD38+ population was associated with a 37% increase in the risk of AIDS (95% confidence interval: 4-81%; p = 0.02). Thus, the percentage CD8+,CD38+ level predicts the development of AIDS independently of the latest CD4 count and beta2M. This assay is therefore potentially useful in conjunction with blood CD4 counts and serum beta2M levels in patient management and clinical trial design.

Predictors of Immunological Failure after Initial Response to Highly Active Antiretroviral Therapy in HIV-1-Infected Adults: A EuroSIDA Study

BACKGROUNDnFactors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined.nnnOBJECTIVEnOur aim was to investigate predictors of immunological failure after initial CD4(+) response.nnnMETHODSnData were from EuroSIDA, a prospective, international, observational human immunodeficiency virus (HIV) type 1 cohort.nnnRESULTSnOf 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value). The incidence of failure was 11.6 incidences/100 person-years of follow-up (95% confidence interval [CI], 10.2-13.4) during the first 12 months and decreased significantly over time (P<.0001). Independent predictors of immunological failure were pre-HAART CD4(+) cell count (per 50% higher; relative hazard [RH], 2.05; 95% CI, 1.83-2.31; P<.0001), time-updated virus load (per 1 log(10) higher; RH, 1.77; 95% CI, 1.64-1.92; P<.0001), and HIV-1 risk behavior (P=.047 for a global comparison of risk groups).nnnCONCLUSIONnThe risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use.

STAGING SYSTEM FOR CLINICAL AIDS PATIENTS

Although there are wide differences in prognosis between patients with AIDS they are often thought of as a single homogeneous group. We think a simple staging system that accounts for important prognostic factors including type and number of AIDS diseases and the CD4 lymphocyte count is required. We followed 363 AIDS patients at the Royal Free Hospital and reported the occurrence of 680 AIDS-defining diseases (ADDs). We measured CD4 counts at approximately monthly intervals. Severity of AIDS diseases was defined a priori on the basis of survival in the AIDS in Europe study of 6578 AIDS patients: mild-oesophageal candidiasis, Kaposis sarcoma (cutaneous), Pneumocystis carinii pneumonia, extrapulmonary tuberculosis; severe-all other ADDs except lymphoma; very severe-lymphoma. The risk of death increased by 15% (p = 0.08) for each mild condition experienced, by 89% (p < 0.0001) for each new severe condition and by 535% (p < 0.0001) when a lymphoma developed. Estimates from the Cox model were used to derive a score reflecting the risk of death. Patient experience was divided into three categories. Patients in AIDS Grade I had an average death rate of one per 10.1 years, compared with one per 2.8 years in AIDS Grade II and one per 1.1 years in AIDS Grade III. Similar rates were seen in an independent validation study on 1230 AIDS patients at different hospital. Our grading system should be useful for patient management, clinical trial design, surveillance, and resource management.

Assessing the cost‐effectiveness of HAART for adults with HIV in England

1 Royal Free Centre for HIV Medicine, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK, 2 NPMS‐HHC, St. Stephens Centre, Chelsea and Westminster Hospital, London, UK, 3 Global Health Outcomes, Glaxo Wellcome R and D, Greenford, Middlesex, UK, 4 Royal Free Centre for HIV Medicine, Department of Thoracic Medicine, Royal Free Hospital, London, UK and Joint Departments of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada

Cervical Abnormality and Sexually Transmitted Disease Screening in Human Immunodeficiency Virus-Positive Women

Objective To determine the incidence of genital tract infections and cervical abnormalities in 185 human immunodeficiency virus (HIV)-positive outpatients with a view toward establishing an effective policy for gynecology screening. Methods Gynecology results were reviewed for 185 HIV-positive women seen as outpatients at the Royal Free Hospital in London. All subjects underwent screening for cervical abnormalities (smear and colposcopy) and sexually transmitted disease (STD) at 6-month intervals for 6 years. The STD prevalence was calculated, and the relationship between the occurrence of STDs and the demography and sexual lifestyle of the women was examined to determine whether these factors were predictive for women at risk for STDs. The incidence of cervical intraepithelial neoplasia (CIN) was determined. We reviewed the use of colposcopy in addition to cytology as a primary screening test to see whether it improved the detection rate of CIN. Results Sixty-five (35.1%) women had a history of previous STDs, and new STDs were detected in 18 women at their first visits. None were detected at subsequent visits. Sexual lifestyle details did not predict women at risk for STDs. Ninety-eight (53%) cervical smears were reported as normal at the first visit, but there was a 3.1% (95% confidence interval 0, 6.6) false-negative rate when compared with colposcopy and directed biopsy. Five of fifty women (10%) with CIN 1 had progressed to higher-grade lesions by 6-month follow-up. Conclusions Given the low prevalence of STDs detected, except for initial screening at presentation, regular, repeat STD screening of HIV-positive women appears to be unnecessary. Because of the high incidence of cervical abnormalities, screening for cervical disease is important, and colposcopy with directed biopsy improved the detection rate of cervical abnormalities.

Participation in clinical studies among patients infected with HIV-1 in a single treatment centre over 12 years

Objectiveu2003 To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV‐positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow‐up visit were included.

Does European or non-European origin influence health care and prognosis for HIV patients in Europe?

Background Previous studies, especially in North America, have shown that socio‐economic factors may influence the prognosis for patients with HIV. This study was performed in order to determine if European or non‐European origin influence provision of health‐care and survival among HIV patients in Europe.

Regional differences in presentation of AIDS in Europe.

Data were collected on 6578 patients diagnosed with AIDS at 52 clinical centres in 17 European countries during an 1-year period from 1979 to 1989. The centres were divided into four regions, North, Central, Southeast, and Southwest. Differences in the incidence of most AIDS-defining opportunistic infections and malignancies were found. After adjusting for known possible confounders, statistically significant differences between regions remained. Pneumocystis carinii pneumonia (PCP) was more common in Northern Europe, Kaposis sarcoma and toxoplasmosis in Central Europe, cytomegalovirus retinitis in South-eastern Europe, and extrapulmonary tuberculosis in South-western Europe. These differences we attribute primarily to different degrees of exposure to the respective underlying pathogens. The prevalence of these and other micro-organisms will determine the clinical course of HIV infections in parts of Eastern Europe and elsewhere where the virus now is spreading.