Showing papers by "Alexander J. McNeil published in 1996"
TL;DR: It is found that HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users, from 1985 through March 1994.
Abstract: Summary We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% Cl 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, Cl 0.1 -0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p=0.0 2 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p=0.0 4 and p< 0.005).
146 citations
TL;DR: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities, and the clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3, while HLA B27 was associated with slower loss ofCD4 cells.
Abstract: Objective : To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. Design and methods : From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group. Main outcome measures : The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution ; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. Results : The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1,B8,DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years ; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found : A1,B8,DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage IF = 0.01). Conclusions : Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.
65 citations
TL;DR: Results indicate re-elevation of square root of CD4 level is associated with treatment but the effect, though significant, is mostly of small magnitude and is possibly transient; models neglecting consideration of treatment fit the checking data almost as well.
Abstract: We fit a class of random effects linear growth curve models for the square root of CD4 count to serial marker data from 164 HIV-positive individuals with known (or accurately estimated) dates of seroconversion and at least 10 CD4 measurements each (median 16). We do so by adopting a Bayesian viewpoint and using the Markov chain Monte Carlo technique Gibbs sampling. In particular, we examine the effect of the antiretroviral treatment zidovudine on the square root of CD4 series for the 136 patients who took the drug. Treatment effects are modelled by positing recoveries in square root of CD4 level proportional to current immuno-competence and changes in slope proportional to current rate of square root of CD4 loss. Both fixed and random treatment effects are considered and models are criticized and compared using Bayesian predictive methodology and checking data which comprise 424 new observations. Results indicate re-elevation of square root of CD4 level is associated with treatment but the effect, though significant, is mostly of small magnitude and is possibly transient; models neglecting consideration of treatment fit the checking data almost as well. Best overall model estimates mean rate of square root of CD4 loss per annum to be 2.1 (standard error 0.12); mean seroconversion value of square root of CD4 is 28.4 (SE 0.65). The estimated variance of individual slopes is 1.9 (SE 0.28), there being considerable individual variation in rate of CD4 loss, and a recovery in level of 0.047 (SE 0.014) times current square root of CD4 level is estimated at treatment uptake.
18 citations