Random effects models for HIV marker data: practical approaches with currently available software.

The analysis of marker data from HIV positive patients has been the motivation for many new developments in applied statistics. As well as reviewing these methods, this paper considers the extent to which programs to implement them are available in current software. Particular areas of development have been the joint modelling of markers and survival outcomes, non-linear random effects models that are of particular relevance for studying the efficacy of treatments and the use of Bayesian computational methods for inference from marker data. The package WinBUGS is recommended as being particularly well suited to the analysis of marker data.

Effect of combination therapy on immunologic progression of human immunodeficiency virus at a population level.

There is accumulating evidence from clinical trials and cohort studies that highly active antiretroviral combination therapy is effective at halting immunologic and clinical progression of human immunodeficiency virus (HIV). Its impact at a population level is less well known because the regimes may be difficult to tolerate and compliance poorer. The authors make use of population data for almost all of the HIV-infected people in Scotland in 1997 who were under clinical care and monitor their response to therapy during the first year when these effective treatments became widely available. More than two thirds of the HIV-positive patients were on some form of antiretroviral therapy during the year. The authors show that all treated groups, even those who were on changing regimes, showed net improvement in immunologic status during the year. For the group of patients on triple or quadruple therapy, there was an average increase of more than 100 CD4 cells/mm(3) over the year, with other treatment groups showing more modest, but significant, increases.

The impact of British and US guidelines for initiating combination antiretroviral therapy on estimating national treatment requirements for HIV-positive patients. Collaborating Immunologists and the Scottish HIV and AIDS Group.

This paper uses comprehensive national data on HIV positive patients in Scotland to carry out a needs assessment exercise for combination antiretroviral therapy. The objective of this study was to estimate the numbers of HIV positive patients in Scotland who would be eligible for combination antiretroviral therapy under current British and US guidelines and to demonstrate the impact of these different guidelines on the resources required. The proportion of the Scottish population that would be eligible for combination therapy ranged from 76% to 91%, under different guidelines for initiating therapy. We thus estimate that for countries such as Scotland, including western Europe and the United States, where a large proportion of the HIV population became infected in the early to mid-1980s, the majority of patients will be eligible for combination therapy, regardless of the guideline.

The recent impact of antiretroviral combination therapy on CD4 counts, AIDS and death in HIV-infected persons: routine HIV surveillance in Scotland.

Our aim was to investigate if the clinical benefits of combination antiretroviral therapy recently reported from clinical trials are reproduced in a population-based HIV surveillance scheme. This surveillance scheme is estimated to cover 90% of the HIV-positive population currently under immunological monitoring in Scotland. Our results showed a considerable reduction in new AIDS cases among this group from 107 in 1995 to 59 in 1996 and an estimated 58 in 1997 (allowing for reporting delay). There was a similar fall in deaths from 75 in 1995 to 59 in 1996 and an estimated 24 in 1997. These observations are temporally associated with increasing prescription of antiretroviral therapy in Scotland throughout 1996 and 1997. Examination of those individuals monitored in both 1996 and 1997 showed that from their first CD4 count in 1996 to their first count in 1997 there has been a median gain of 6 CD4 cells/mm3 (95%CI 0-12) compared with a median fall of 27 CD4 cells/mm3 (95%CI -35, -17) for those monitored in both 1995 and 1996. Highest median gains in CD4 cell counts from 1996 to 1997 were seen in those receiving triple or quadruple therapy (median gain 32CD4 cells/mm3). These results are further strengthened by the results of a separate longitudinal analysis showing a highly significant (P < 0.001) effect of treatment on CD4 cell loss with the highest mean CD4 gains being seen in those in triple or quadruple therapy. Our results indicate that the benefits of combination antiretroviral therapy previously seen in clinical trials are being reproduced at a population level. It remains to be seen if these benefits can be sustained in the long term.

Deaths, HIV infection, abstinence, and other outcomes in a cohort of injecting drug users followed up for 10 years.

OBJECTIVE: To trace, follow up, and interview a group of patients known to be injecting drug users in order to establish current drug taking and other features related to drug use over 10 years. DESIGN: Descriptive follow up study of a cohort of injecting drug users established between 1982 and 1985. SETTING: General practice based patient population study initially, with later tracing of subjects throughout the United Kingdom through NHS Central Registries and current general practitioners. SUBJECTS: 203 injecting drug users recruited up to December 1985. MAIN OUTCOME MEASURES: Survival, cause of death, abstinence, or continued drug use; HIV status; and demographic variables. RESULTS: Of the 203 injecting drug users recruited into the study, over half were known to be HIV positive and 42 died of various causes (increasingly AIDS). From the start of follow up in 1990, 163 (91%) of the 180 survivors were traced, of whom 116 (71%) were interviewed. Dramatic changes had occurred in drug taking, with a move away from injecting towards oral drug use. A few patients, however, continued to inject. 90 (78%) of those interviewed had been in prison, of whom 37 (41%) had injected drugs while in prison. CONCLUSIONS: The pattern of deaths had changed from being largely due to overdose in the early 1980s to predominantly AIDS related in later years. The reduction in deaths due to overdose may have been connected with but was not always causally related to a new approach by legal, social, and medical services. Drug use continues in a modified form in a large proportion of patients followed up. As a group, drug users require long term support for a multiplicity of problems.