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Background:  Whether the relationship between the HIV RNA/CD4 count and risk of clinical disease continues to hold true for newer antiretroviral drugs is unknown because drugs licensed after 1997 have been approved on the basis of clinical trials assessing only short-term surrogate endpoints. We hypothesised that virologic and immunologic markers have the same meaning in terms of long-term clinical effect according to different drug regimens, rather than, for example, newer drugs having an additional effect leading to a higher or lower risk of AIDS or death for given HIV RNA/CD4 levels when compared with others.

Methods:  Analysis included patients taking combination-antiretroviral-therapy (CART) regimens containing 2 non-abacavir (ABC) nucleosides plus a third drug of a non-nucleoside reverse transcriptase inhibitor (NNRTI), a (possibly ritonavir-boosted [r]) protease inhibitor (PI) or ABC. We compared rate ratios of AIDS and death at given, latest HIV RNA and CD4 counts levels according to the nucleoside pair and specific third drugs patients received as antiretroviral therapy. In multivariate analysis we adjusted for latest CD4 count, HIV RNA, age, exposure group, prior AIDS, calendar year, time from starting CART, time on current combination.

Results:  Among a total of 9802 patients, 6814 were included in this analysis and contributed a total of 22,766.6 person-years of follow-up. Over follow-up, median CD4 count was 353 cells/µL, HIV RNA 199 copies/mL. Over follow-up, 889 events of new AIDS or death occurred, of which 125 were death. AIDS/death incidence rates for any given CD4 or HIV RNA category were similar regardless of specific drugs being used. Adjusted rate ratios for individual drugs compared with indinavir (IDV) (for which clinical endpoint trials are available) were all close to 1 and with relatively narrow 95% confidence intervals (CI) all overlapping 1; e.g., nelfinavir (NFV) rate ratios 0.99 (95% CI 0.76 to 1.28); efavirenz (EFV) rate ratios 0.83 (0.57 to 1.20); ABC rate ratios 1.01 (0.64 to 1.60); table. Results were similar for different nucleoside pairs with adjusted rate ratios overlapping 1 when compared with other.

Conclusions:  The results indicate that AIDS and death rates for given CD4 count and HIV RNA categories are similar, regardless of CART regimen being taken. This provides reassurance that HIV RNA- and CD4-values in individual patients receiving newer drugs have the same meaning in terms of AIDS/death risk, regardless of specific antiretroviral regimen.

Keywords: AIDS/death clinical endpoint; CD4/HIV-RNA surrogate markers; CART specific regimens