Update on the virologic and immunologic response to highly active antiretroviral therapy
Highly active antiretroviral therapy (HAART) delays clinical progression by suppressing viral replication, measured by a substantial reduction in HIV RNA, allowing the immune system to reconstitute, measured in most studies by an increase in CD4 cells. These virologic and immunologic consequences do not occur uniformly among HAART users. Markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while receiving HAART. In this report, we review studies describing the heterogeneous virologic and immunologic progression after the initiation of HAART, discuss methodologic concerns in the study of the response of biomarkers, and update findings obtained in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of antiretroviral therapy, and age at the time of initiation are independent determinants of response.
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References and Recommended Reading
- 6.Yamashita TE, Phair JP, Munoz A, et al.: Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study. AIDS 2001, 15:735–746. This is an earlier analysis of short-and long-term HIV RNA and CD4 cell count response to HAART in MACS, which showed that best response was seen among patients without experience to any component of HAART. Baseline CD4 cell count was a predictor of response, and age effects were restricted to early recovery of CD4 cells after HAART initiation.PubMedCrossRefGoogle Scholar
- 8.Le Moing V, Chene G, Carrieri MP, et al.: Clinical, biologic, and behavioral predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors. J Acquir Immune Defic Syndr 2001, 27:372–376.Google Scholar
- 43.Pakker NG, Kroon ED, Roos MT, et al.: Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group. AIDS 1999, 13:203–212. This is a report from the EuroSIDA Study Group showing that the increase in CD4 cell counts in the 3 years after HAART initiation occurred more rapidly among younger participants.PubMedCrossRefGoogle Scholar
- 44.Kaufmann GR, Perrin L, Pantaleo G, et al.: CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 2003, 163:2187–2195. This is a report from the Swiss HIV Cohort Study in which younger age was associated with better CD4 response among patients with advanced disease. A lack of sustained HIV-RNA suppression, treatment interruptions, and older age were associated with a poorer CD4 T-cell response within 4 years after HAART initiation.PubMedCrossRefGoogle Scholar
- 48.Deeks SG, Barbour JD, Grant RM, Martin JN: Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS 2002, 16:201–207. This is a clinic cohort study showing that among patients with virologic failure but good CD4 response after HAART initiation, approximately 50% of the participants experienced a subsequent decrease in CD4 cell counts to pretherapy levels by 3 years after virologic failure. Change in HIV RNA from pretreatment levels and discontinuing therapy were independent predictors of subsequent CD4 decline among these individuals with discordant responses.PubMedCrossRefGoogle Scholar