Discordant Immunological and Virological Response to Antiretroviral Therapy Linked to Higher Mortality

		SUMMARY: HIV positive people in Africa and South America who experienced viral load suppression without CD4 cell recovery, or vice versa, after starting antiretroviral treatment -- known as discordant response -- were more likely to die, researchers reported in the January 1, 2010 Journal of Acquired Immune Deficiency Syndromes. These results from resource-limited settings agree with previous findings from high-income countries.

By Liz Highleyman

Suely Tuboi from Universidade Federal Fluminense in Brazil and colleagues evaluated mortality associated with patterns of virological and immunological (increased CD4 count) response 6 months after starting combination antiretroviral therapy (ART).

The investigators evaluated 7160 HIV patients age 16 and older from resource-limited countries in Africa and South America who initiated ART between 1996 and 2007. Participants contributed a total of 15,107 person-years of follow-up.

Participants had at least 1 measurement of plasma viral load or CD4 cell count within 3-9 months after starting treatment. Response was categorized as complete (viral load suppression and CD4 cell recovery), discordant (either virological only or immunologic only), and absent (neither type of response).

In a multivariate analysis adjusted for age at ART initiation, year of ART initiation, baseline clinical stage, baseline CD4 cell count, and occurrence of an AIDS-defining condition within the first 6 months of treatment, the researchers found that either discordant or absent response to therapy were associated with increased risk of death.

"Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries," the investigators concluded.

In a study published in 2008, researchers from the University of Alabama found that 9% of patients achieved only virological response and 16% achieved only immunological response. Both types of discordant response were significantly associated with earlier progression to AIDS or death.

The African DART trial found that people in resource-limited settings can benefit from ART even without laboratory monitoring; however, a recent World Health Organization study showed that basing treatment decisions on CD4 count alone, without viral load monitoring, led to both missed cases of virological failure and unnecessary treatment switches when current drugs were suppressing viral load.

The results of the present study, the authors wrote, "support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings."

Departamento de Epidemiologia e Bioestatística, Universidade Federal Fluminense, Niterói, Brazil.

1/29/10

Reference
SH Tuboi, AG Pacheco, LH Harrison, and others. Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings. Journal of Acquired Immune Deficiency Syndromes 53(1): 70-77 (Abstract). January 1, 2010.