Small number of UK HIV-positive patients at risk of exhausting treatment options

A small but growing proportion of HIV-positive patients in the UK may be in danger of exhausting current treatment options, according to the authors of a paper published online by the British Medical Journal on Friday. However, despite increased exposure between 1996 and 2002 to all three major classes of antiretrovirals, the HIV population as a whole have much improved CD4 counts and viral loads.

Investigators working together on the UK Collaborative HIV Cohort (UK CHIC) analysed immunological and virological data, as well the treatment history, of 16,593 adults who had attended one of six large HIV treatment centres in London and Brighton between January 1^st 1996 and December 31^st 2002. Most were male (80.6%), the majority were infected through gay sex (62.3%) or heterosexual sex (26.7%), the median age at first study visit was 34 years (interquartile range 29-39), 56% were white, 18% were African, 12.7% were of other ethnicities and ethnicity was unknown for 13.9%.

Overall, 10,207 of the 16,953 (61.5%) had ever been exposed to antiretroviral drugs; 10,176 (61.3%) to nucleoside reverse transcriptase inhibitors (NRTIs), 5657 (34.1%) to protease inhibitors (PIs), (41.3%) 6857 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 450 (2.7%) to the fusion inhibitor, enfuvirtide (T-20, Fuzeon).

By the end of 2002, patients had been exposed to an average of four drugs (range 0-16) and the proportion of patients exposed to any antiretroviral therapy had risen from 41.2% to 71.3%. Similarly, those exposed to PIs increased from 14% to 40.7% and NNRTI exposure increased from 3.8% to 53.5% over the study period.

The median CD4 count of the cohort as a whole rose each year – from 270 cells/mm³ in 1996 to 408 cells/mm³ in 2002. In addition, the proportion with moderate-severe immunosuppression (CD4 counts below 200 cells/mm³) fell from 38% to 13.3% over the same period. Viral load improved over time as well, from 4.34 log₁₀ copies in 1996 to 1.89 log₁₀ copies in 2002. Among patients who had ever received antiretroviral therapy, the proportion with a CD4 count below 200 cells/mm³ fell from 57.1% in 1996 to 15.3% in 2002.

The percentage of patients who had ever taken antiretroviral therapy and who had been exposed to all three main classes of drugs increased from 2.3% in 1996 to 38.3% in 2002. Between 1996 and 2000 the proportion of patients who experienced treatment failure with all three main classes of drugs increased from 0% to 15.4%. However in 2001 and 2002 the numbers remained steady at 15.8% and 15.3, respectively. Although a high percentage of this group had moderate-severe immune suppression (between 46-58% in the years 1997-1999), the immune systems of this group appeared to be improving over time; in 2002 32.5% had a CD4 count below 200 cells/mm³.

The authors believe that these findings “reflect the increasing number of new drugs that become available each year and the growing emphasis that is now placed on achieving good adherence, even in patients who have previously experienced problems when taking these drugs.

“However,” they continue, “the immunological and virological status of patients who have experienced three class failure remains relatively poor, showing that for a small number, treatment options are in danger of becoming exhausted.

“New drugs with low toxicity, which are not associated with cross resistance to existing drugs,” are urgently needed for such patients, the authors conclude.