Some groups get more benefit from anti-HIV drugs than others

Some groups of patients appear more likely to derive a benefit from antiretroviral therapy in the first year of treatment than others, a study published in the November 18^th edition of AIDS has established. Investigators from the Antiretroviral Therapy (ART) Cohort Collaboration, which involves clinics in Europe and North America, found that the rate of new AIDS diagnosis declined more rapidly amongst gay men than other HIV risk groups and that individuals who had an AIDS diagnosis when they started anti-HIV therapy had the least rapid decline in new AIDS events.

The researchers suggest that patients from groups which experienced a less rapid decline in the incidence of new AIDS-defining illness after starting HIV therapy should receive close monitoring, even if they have a good increase in their CD4 cell count and fall in their viral load after six months.

Anti-HIV therapy has been shown to significantly reduce the incidence of AIDS and death; indeed earlier data from the ART investigators showed that new AIDS events fell by over two-thirds in the first three years of treatment with potent anti-HIV therapy.

However, earlier analyses did not examine whether the decline in new AIDS events applied equally to all the groups affected by HIV. The investigators therefore looked at the rate of new AIDS events amongst patients with different demographic and clinical characteristics and assessed whether the decline in AIDS events over the first year of treatment differed according to these characteristics.

AIDS-defining illnesses were divided according to whether they occurred in the first six months after HIV treatment was started or the next six months. The investigators gathered information on individuals’ sex, age when HIV treatment was started, HIV risk group, baseline CD4 cell count and viral load, type of anti-HIV regimen, and the year antiretroviral therapy was initiated.

A total of 22,217 patients were included in the investigators’ analysis. A quarter were women, 40% were gay or bisexual men, 36% were infected with HIV through heterosexual intercourse, and 16% by injecting drug use. AIDS had been diagnosed in 23% of patients prior to antiretroviral therapy being started.

The median age when treatment with potent anti-HIV therapy was started was 37 years. Median CD4 cell count at treatment initiation was 234 cells/mm³ and median viral load was 80,000 copies/ml. Two-thirds of patients started treatment with a regimen containing a protease inhibitor.

Over the first year of treatment, a total of 1521 new AIDS-defining events were recorded and 414 patients died. The overwhelming majority of these new AIDS events (1185) occurred during the first six months of treatment, with only 336 recorded during the second six month period of potent HIV therapy.

The overall incidence of AIDS was 8 per 100 person years of follow-up. However, this rate differed dramatically according to time period. The event rate in the first six months was 12 per 100 patient years, falling by 68% to 4 per 100 patient years in the second six months, a statistically significant decline (p = 0.0001).

Although AIDS events declined dramatically in all demographic groups, the decline was steeper in some groups than others. For example, the investigators noted that new AIDS events fell by 77% between the two six month periods in gay men, but by only 56% amongst injecting drug users.

Rates of decline were more rapid for gay men (p = 0.002), individuals who initiated anti-HIV therapy after 2001 (p = 0.03), patients who started HIV treatment with a CD4 cell count below 350 cells/mm³ and those who started taking anti-HIV drugs when their viral load was above 100,000 copies/ml (p = 0.0008).

By contrast, the rate of decline was significantly slower amongst patients who had an AIDS diagnosis at baseline (p = 0.0007).

The investigators offer several possible explanations for these findings. They suggest that adherence may have been better amongst groups with the steepest decline, but note that they did not record data on this. Another possible reason offered was social and economic differences between groups.

They comment, “although the rate of decline of AIDS events is dramatic in the first year after starting HAART, declines in incidence vary according to patients’ characteristics…in particular, homosexual men experience more rapid declines in incidence of AIDS than those from other risk groups and those with prior a prior diagnosis of AIDS experience less rapid declines in incidence.” They add, “to our knowledge, this is the first study to document different rates of decline in different patient groups.”

A study published in the same edition of AIDS has found that survival amongst individuals diagnosed with AIDS has increased significantly since 1984. Investigators analysed data from a cohort of over 1500 gay men and a separate cohort of 461 women. They found that in the period when their was either no anti-HIV therapy or only AZT monotherapy, within six months of receiving an AIDS diagnosis a quarter of patients died. However, by 2001 – 2003 (when the use of combinations of anti-HIV drugs was well established), the period required for 25% mortality amongst patients receiving an AIDS diagnosis was over five years.