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Second-line Regimens Twice as Likely to Fail as Initial Therapy

Treatment failure is twice as likely with second-line antiretroviral regimens compared with initial therapy, according to a study presented at the recent 9th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland.

Colette Smith and colleagues analyzed treatment outcomes among patients at the Royal Free Hospital in London who were antiretroviral-naive when they started their first HAART regimen consisting of at least 3 drugs.

A total of 166 participants subsequently experienced virological failure on their first regimen (at least 1 viral load > 400 copies/mL after more than 4 months of continuous therapy), started second-line antiretroviral therapy (defined as at least 1 new PI or NNRTI and/or at least 2 new NRTIs), and experienced virological failure a second time.

Time to virological failure -- defined as the first of 2 consecutive viral loads > 400 copies/mL more than 4 months after starting the second-line regimen -- was calculated using survival analysis.


• At the time the second regimen was started, the median CD4 count was 256 cells/mm3 and the median viral load was about 4 log copies/mL.

• 15% of patients started a second-line regimen that included 1 new drug they had not previously used, 29% started 2 new drugs, and 56% started 3 or more new drugs.

• Compared with those starting a second-line regimen containing only 1 new drug, adjusted hazard ratios for treatment failure were 0.56 for those starting 2 new drugs and 0.50 for those starting 3 or more new drugs (P = 0.001).

• Each additional year from first virological failure to the start of second-line therapy was associated with a 19% reduced hazard of treatment discontinuation (P = 0.04).

• 29% of patients starting a second regimen experienced virological failure by 12 months, and 44% did so by 36 months.

• In comparison, 14% of patients starting a first-line regimen experienced virological failure by months, and 27% did so by 36 months.

• In a multivariate analysis, the following factors were independently associated with virological failure:

• Fewer new antiretroviral drugs in the second-line regimen (HR 0.1 for 2 drugs compared to 1; HR 0.26 for > 3 new drugs) (P = 0.01);

• Lower CD4 count (HR 0.73 per 100 cells/mm3; P = 0.03);

• Higher viral load when starting the second-line regimen (HR 2.56 per 1 log; P = 0.005).

Based on these findings, the investigators concluded, "The median time to making at least one antiretroviral switch on a second-line regimen was comparable to that seen on first-line regimens."

"Although virologic failure appeared more common on second-line than on first-line regimens, perhaps because this is a group who are more predisposed to virologic failure," they continued, "response rates were still excellent."

University College Medical School, London, UK; Royal Free Hospital, London, UK.



CJ Smith, FC Lampe, M Youle, and others. Treatment discontinuation and virological failure amongst HIV-positive individuals starting second-line combination antiretroviral therapy (cART). 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1):O333. November 10, 2008.