SUMMARY: African-Americans had a 40% greater likelihood of virological failure on antiretroviral therapy even after controlling for known risk factors, according to a meta-analysis of ACTG trials presented at CROI 2011.

By Liz Highleyman

Several studies over the course of the HIV/AIDS epidemic have found that blacks (and perhaps also Hispanics/Latinos) do not respond as well as whites to antiretroviral therapy (ART).

Some analyses have indicated that this disparity is attributable to socio-demographic factors and less access to care, but others suggest such differences remain even when researchers try to control for these factors.

At the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston, Heather Ribaudo from Harvard School of Public Health presented findings from an analysis of racial differences in treatment response among participants in 5 studies conducted by the AIDS Clinical Trials Group (ACTG) between 1998 and 2005.

The analysis included 2495 previously untreated non-Hispanic white (n = 1344) and black (n = 1151) participants who initiated ART in these 5 trials. Studies were mostly done in the U.S. and each included 30%-40% black enrollees. Most participants (about 80%) were men and the average age was 37 years. About two-thirds used 3-drug ART regimens containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a protease inhibitor.

Ribaudo and colleagues looked at rates of virological failure, or inability to achieve and maintain undetectable viral load on combination ART, after adjusting for a variety of factors thought to influence treatment response, including age, sex, disease status, co-morbidities, mode of HIV transmission, depression, education level, alcohol use, "self-efficacy," and perceived social support.

Results

	Overall, 45% of black participants and 32% of white participants experience virological failure, defined as viral load > 1000 copies/mL at week 16-24 or > 200 copies/mL after 24 weeks.
	In an intent-to-treat analysis, black participants had a significantly higher risk of virological failure compared with white patients (hazard ratio 1.6, or 60% greater risk).
	This difference was consistent across different types of ART regimens.
	The difference was reduced after adjusting for known potential confounders, but blacks still had a significant 40% higher risk of virological failure (hazard ratio 1.4).
	Results were similar in an as-treated analysis looking at actual -- rather than assigned or intended -- treatment regimen.
	In addition to race, other factors associated with increased risk of virological failure included:
	Younger age; Lower baseline CD4 T-cell count; Higher baseline HIV RNA level; Less education; Hepatitis C coinfection; Recent non-adherence.
	Unlike some past studies, this analysis saw no association between virological failure and sex or alcohol use.
	Despite increased risk of virological failure, however, black participants showed greater CD4 cell gains over 96 weeks (though not at 24 or 48 weeks).
	After adjusting for other factors including baseline CD4 count, blacks gained an average 33 cells/mm3 more than white participants.

Based on these data, the researchers concluded, "In these ACTG studies, black race was associated with a 40% higher risk of virological failure on initial ART regimens than white race."

"This finding did not appear to be explained by recent adherence and potential confounding demographic, medical, or social factors that were measured," they continued.

At a CROI press conference Ribaudo noted that link between black race and poorer treatment was response was "very robust" and "very consistent," even when attempting to control for factors associated with treatment access. However, she noted, this analysis was not able to address all factors related to access to care, nor did it analyze genetic differences.

"We were not able to capture some key social factors that might be a measure of more challenging life situations that patients might face, such as housing status, income level, and the number of dependents in a family," Ribaudo said.

Differences in virological failure rates were observed across a broad range of regimens, making it less likely that differences are due to pharmacogenetic associations, she added.

Investigator affiliations: Harvard School of Public Health, Boston, MA; Rush Univ Medical Ctr, Chicago, IL; Harvard Medical School, Boston, MA; Johns Hopkins Univ, Baltimore, MD; Univ of California, San Diego, CA; Univ of Miami Miller School of Medicine, Miami, FL; Univ of Pittsburgh, PA; Weill Cornell Medical College, New York, NY.

3/25/11

Reference
H Ribaudo, K Smith, G Robbins, et al. Race Differences in the Efficacy of Initial ART on HIV Infection in Randomized Trials Undertaken by ACTG. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 50.