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

Abstract

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.

Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV

“…The meta-analysis of phases II and III randomized clinical trials by Adult AIDS Clinical Trials Group (ACTG) indicated that a mean gain of 30-40 CD4 cells above baseline was associated with high probability that there will be no progression to AIDS or death (Hughes et al, 1998). Similarly, the impact of combination therapies on reduction of new AIDS cases and death rates in Scotland was significantly associated (p < 0.001) with the median gain of 32 CD4 cells above baseline (Allardice et al, 1998). Thus, a V1-induced rise in mean or median CD4 cells, whether in absolute or percent terms, is likely to be clinically beneficial.…”

Adapting portfolio theory for the evaluation of multiple investments in health with a multiplicative extension for treatment synergies

“…For example, combination drug therapies have been demonstrated to be more effective than monotherapy in the treatment of HIV [8] and of unstable angina [9]. Thus a general model for the evaluation of multiple interventions should incorporate possible synergistic effects.…”

“…Var (A i B i ) depend on the joint distribution of A i and B i , but in the case where they are normally distributed it is possible to give formulae for these in terms of µ Ai , µ Bi , σ Ai , σ Bi and ρ i (see 'Appendix B').The total gain in health for the population will be given as: (7) with mean: (8) and variance: (9) …”

“…Hawe and Shiell [1] state that 'portfolio theory suggests that by deliberately diversifying the portfolio and including high-risk investments along with the safer bets, overall returns will be higher'. While this comment remains unsubstantiated, there is some evidence that the bundling of health interventions can increase the effect in terms of health gain beyond the linear combination of the parts [8,9,10].…”

Short-term physical and emotional health outcomes of public sector ART in the Free State province of South Africa

“…As has been observed in many industrialised countries, provision of ART via the public health system can transform AIDS from a fast, insidious killer into a more manageable, though still incurable, chronic illness [2][3][4][5][6][7][8]. By reducing the associated morbidity and mortality, ART has had a dramatic impact on the quality of life (QoL) of people living with HIV/AIDS (PLWHA), thus engendering numerous socio-medical studies [9][10][11][12][13][14][15].…”