Can early antiretroviral therapy fully restore health? Workshop on Pathogeneses and Management of Long-Term Complications of ART IAS Conference, Rome July.

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Presentation transcript:

Can early antiretroviral therapy fully restore health? Workshop on Pathogeneses and Management of Long-Term Complications of ART IAS Conference, Rome July 18, 2011

Trends in death rate in people with HIV: UK Source: Health Protection Agency Year Rate per 100 people Number of deaths in year Number seen for care in year

People on ART > 6 months: proportion with viral load > 50 copies/mL Royal Free clinic cohort. Smith C, Lampe F, Johnson M, unpublished

HIV and risk of non-AIDS diseases and death - HIV leads to increased risk of a variety of serious non-AIDS conditions - Such risk is generally associated with lower CD4 count - So what is the extent of ongoing increased risk of serious events associated with HIV if the CD4 count is high ? - Impossible to answer definitively, due to likely selection and confounding effects in studies comparing with HIV uninfected people.

Comparison of death rate in HIV positive and HIV negative people: FRAM 469 HIV infected, 280 sero-negative controls Hazard ratio* Overall 3.4 (95% CI: 1.35, 8.5); p = Current CD4 > (95% CI: ); p = 0.13 *adjusted for cardiovascular risk factors Cockerham et al; JAIDS 2011

Myocardial Infarction rates compared with general population: Kaiser-Permanante database Klein et al; CROI 2011 HIV +ve: 90,961 HIV –ve: 1,133,444 Relative 95% CIp-value rate MI overall <0.001 CHD overall <0.001 CD4 > 500, on ART CD4 > 500, not on ART

Death rates in ART naïve MSM with CD4 count above 350 cells/mm 3 compared with the general population Deaths Person- Death rateSMR (95% CI) years / 1000 pyrs , (1.06 – 1.58) Lodwick et al; Lancet 2010 CD4 count > 500/mm 3 : SMR 1.03 (0.76 – 1.37) Focus on MSM due to lesser potential for confounding

Lewden et al, COHERE, EACS Cologne, 2009 See also Zwahlen et at IJE, 2009 Death rate in ART-experienced MSM with CD4 count > 500, compared with the general population n ~ 28,000 MSM Previous AIDS No previous AIDS >60 Age 5 yrs 4 yrs 3 yrs 2 yrs 1 yr SMR Time with CD4 > 500 Current

SMRs for non-AIDS deaths in non-IDU in SMART and ESPRIT control groups compared with the general United States population - Viral load 350 in past 6 months Person-yrs 15,324 Observed deaths 62 Expected deaths SMR (95% CI) 0.99 ( ) Rodger et al, SMART and ESPRIT, unpublished

Conclusions The extent of any increased risk of of death due to HIV in those with current CD4 count > 500 remains unclear, but appears to be modest, particularly if: - viral load is suppressed - no history of AIDS / low CD4 count

Acknowledgements Investigators in the following studies: SMART ESPRIT Royal Free clinic cohort D:A:D CASCADE COHERE Health Protection Agency (HPA), UK