UK patients risk treatment exhaustion

The proportion of HIV-infected individuals receiving highly active antiretroviral therapy (HAART) has steadily increased in the UK since 1996, but a 'substantial proportion' of these patients may be in danger of running out of treatment options, researchers say (BMJ 2005; 330:695-699.)

Around 40% of patients under follow-up have been exposed to all three of the main classes of antiretroviral drugs, and so are potentially at risk, epidemiologist Caroline Sabin of the Royal Free and University College Medical School told AIDS. But a very small percentage of patients, less than 5%, are actually showing signs of treatment exhaustion.

Sabin and colleagues came to their conclusions after analysing the clinical records of 16 593 HIV-positive individuals, mostly men, who received medical care between 1996 and 2002 at six large HIV treatment centers in southeast England. Overall, 10 207 of the patients, or 61.5%, had received some form of antiretroviral therapy, with the percentage increasing from 41.2% in 1996 to 71.3% in 2002. Not surprisingly, the researchers found the average CD4 cell count and HIV RNA burden of patients under follow up had improved each year, changing from 270 × 10⁶ cells/l and 4.34 log₁₀ copies/ml in 1996 to 408 × 10⁶ cells/l and 1.89 log₁₀ copies/ml, respectively, in 2002.

But the proportion of patients who had been exposed to all three of the main classes of HAART drugs - nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors - and, thus, were at risk of exhausting treatment options, rose each year as well. By 2002, 3060 out of 7987 HIV-positive individuals under treatment, or 38.3%, had been exposed to all three classes of anti-HIV drugs. Of these patients 467 (15.3%) had previously experienced virological failure on all three drug classes, and some of these 'at risk' patients were showing signs of treatment exhaustion. Specifically, 150 patients (1.9%) had CD4 cell counts below 200 × 10⁶ cells/l, and 210 individuals (2.6%) had HIV RNA measurements greater than 2.7 log₁₀ copies/ml.

However, the UK researchers found that the incidence of triple-class antiretroviral drug failure has remained fairly stable since 2000. That finding adds to conflicting conclusions of two other recent studies. Late last year, researchers with the EuroSIDA Study Group reported an increase in virological failure in a longitudinal study of 3496 HIV-positive patients. And at the Twelfth Conference on Retroviruses and Opportunistic Infections in February, Danish researchers reported that the risk of triple-class antiretroviral drug failure was on the decline in Denmark based on the clinical data of all HIV-positive individuals receiving antiretroviral therapy in that country. One thing is consistent, though, Sabin says about the studies the incidence of triple class failure seems to be pretty low at the moment.