Using baseline CD4 cell count and plasma HIV RNA to guide the initiation of highly active antiretroviral therapy

Conflicting evidence regarding the impact of baseline plasma HIV RNA and CD4 cell count on survival after the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients has resulted in wide variability in the expert recommendations regarding the when to start therapy. Early initiation of HAART may result in avoidable toxicities and premature evolution of resistance, whereas delaying HAART may increase the risk of opportunistic infections and/or preclude a worse virological and clinical response to therapy. While there is widespread consensus that HAART can be delayed to a CD4 cell count of 0.350 x 10 9 cells/L, the range between this threshold and 0.200 x 10 9 cells/L remains controversial. Greater uncertainty surrounds the role of baseline plasma HIV RNA, with some guidelines recommending initiating HAART when this level rises above 55,000 c/mL regardless of baseline CD4 cell count. The following review examines the evidence in support of delaying the initiation of HAART to a CD4 cell count of 0.200 x 10 9 cells/L regardless of plasma HIV RNA levels and outlines supporting data from a Canadian prospective cohort study of antiretroviral naïve patients treated with HAART. KEY WORDS. Plasma viral load. Adherence. Viral load supression. Virologic failure. Survival.

La carga viral plasmática y el nivel de los linfocitos CD4+ en la sangre son marcadores biológicos de alto valor pronóstico, en lo que se refiere a la historia natural de la infección por HIV. Esto ha sido demostrado en forma terminante en pacientes no tratados. El impacto y valor relativo de dichos marcadores en el pronóstico de pacientes que inician terapia antirretroviral no está totalmente aclarado. Esto ha generado opiniones diversas en la literatura médica, especialmente en lo que se refiere a las recomendaciones para el inicio del tratamiento en pacientes asintomáticos. Existe acuerdo general que el inicio del tratamiento se puede demorar hasta que los linfocitos CD4+ están en un nivel de 0.350 x 10 9 cells/L. Nuestros resultados, basados en una cohorte prospectiva canadiense, demuestran que es aceptable demorar el inicio del tratamiento hasta que los linfocitos CD4+ están en un nivel de 0.200 x 10 9 cells/L sin importar el nivel de la carga viral plasmática.

Extent to which low-level use of antiretroviral treatment could cure the AIDS epidemic in sub-Saharan Africa

Despite growing international pressure to provide HIV-1 treatment to less-developed countries; potential demographic and epidemiological impacts have yet to be characterised. We modelled the future impact of antiretroviral use in south Africa from 2000 to 2005. methods: We produced a population projection model that assumed zero antiretroviral use to estimate the future demographic impacts of the HIV-1 epidemic. We also constructed four antiretroviral-adjusted scenarios to estimate the potential effect of antiretroviral use. We modelled total drug cost; cost per life-year gained; and the proportion of pe-person health-care expenditure required to finance antiretroviral treatment in each scenario. Findings: With no antiretroviral use between 2000 and 2005; there will be about 276000 cumulative HIV-1-positive births; 2;302;000 cumulative new AIDS cases; and the life expectancy at birth will be 46.6 years by 2005. By contrast; 110;000 HIV-1-positive births could be prevented by short ourse antiretroviral prophylaxis; as well as a decline of up to 1 year of life expectancy. The direct drug costs of universal coverage for this intervention would be US$54 million - less than 0.001of the per-person health-care expenditure. In comparison; triple-combination treatment for 25of the HIV