More evidence from UK of improvements in prognosis since advent of HAART, but concern over late diagnosis

The risk of death for individuals seroconverting with HIV in the UK has fallen by 97% since the introduction of potent antiretroviral therapy in 1996, according to a study published in the January 2^nd 2008 edition of AIDS. The study also showed that 94% of individuals newly infected and diagnosed with HIV in the UK can now expect to be alive ten years later.

Injecting drug users had a worse prognosis than other risk groups, even though they have a good virological response to treatment when they access it. The investigators mainly attribute injecting drug users' increased risk of death to coinfections such as hepatitis B virus and hepatitis C virus.

Although the investigators are generally optimistic about their findings, and believe they represent the best-possible outcomes that currently available anti-HIV drugs can achieve, they nevertheless express concern at the high levels of undiagnosed HIV in the UK. They note that over 10% of patients newly-diagnosed with HIV have been diagnosed so late they have already progressed to AIDS.

When potent anti-HIV therapy became available in 1996 it transformed HIV in the UK (and similar countries) from being an illness associated with a short prognosis to a manageable illness with long-term survival.

The extent to which potent antiretroviral therapy was revolutionising the long-term outlook for HIV-positive individuals was realised as early as 2001, when it was estimated that 87% of HIV-infected individuals could expect to be alive ten years after infection.

Since 1996 there have been significant advances in the management of HIV-positive patients, and newer, more potent, less toxic, and easier to take drugs have been developed. But it is unclear if this progress will translate into an improvement in prognosis because of drug resistance and the serious long-term treatment side-effects of some antiretroviral drugs such as cardiovascular disease.

A small number of HIV-positive patients are diagnosed very soon after they are first infected with the virus. These individuals provide a unique opportunity to assess long-term changes in the prognosis of HIV-infected individuals.

Investigators from the UK Register of HIV Seroconverters therefore performed a study to provide survival estimates and changes in the risk of death over time for a cohort of 2263 patients followed in the UK from their seroconversion.

These patients had a median age of 30 years. Sex between men was the HIV risk activity for 81% of individuals, but the proportion of patients infected due to heterosexual sex increased from 8% before 1996 to 19% in 2004 – 06.

Between the establishment of the cohort in 1994 and 2006, 444 (20%) patients died.

Compared to the period before potent anti-HIV therapy became available, the risk of death in the 1996- 97 period was 0.63 (95% confidence interval [CI], 0.48 – 0.81) and decreased in each succeeding two year calendar interval to a risk of 0.03 in 2004 – 06 (95% CI, 0.02 – 0.06).

Older age at seroconversion (hazard ratio [HR], 1.49 for each ten year increase; 95% CI, 1.34 – 1.66, p

There was no difference in the risk of death for patients infected through sex between men and heterosexual sex.

Although there was no significant difference in prognosis between individuals infected through injecting drug use and those infected through sex between men in the era before effective anti-HIV treatment, this changed over time. By 2004 – 06, injecting drug users had a much greater risk of death (HR, 7.45, 95% CI, 4.26 – 13.05) than gay men. The investigators found that only 45% of injecting drug users had initiated anti-HIV therapy five years after diagnosis compared to 57% of gay men, but when anti-HIV therapy was used, injecting drug users and gay men spent equal amounts of time with a viral load below 1000 copies/ml. The investigators believe that injecting drug users had a higher risk of death because of coinfection with hepatitis B or hepatitis C virus.

Before 1996, the proportion of patients expected to live for five, ten and 15 years following infection with HIV was 87%, 50% and below 28% respectively. By 2000 – 2006 the proportions had increased to 99%, 94% and 89% respectively. Survival improved across all age groups, but was particularly marked in the over-45s.

The proportion of deaths directly attributable to AIDS fell from 31% before 1996 to 15% in 2000-2006.

Unsurprisingly, the use of potent antiretroviral therapy increased over time from less than 2% before 1996 to 58% in 2004 – 06. When the investigators restricted their analysis to patients seroconverting after 2000, they found that the median time from diagnosis to initiation of potent anti-HIV therapy was 3.9 years. A wider analysis of the entire cohort showed that there was a significant shortening of time between seroconversion and starting anti-HIV therapy (p = 0.001). They think that this could be either because patients were receiving treatment during primary infection or because doctors were initiating therapy earlier than British treatment guidelines recommend.

In the 1996 – 97 period most patients (62%) starting anti-HIV therapy did so with a regimen based upon an unboosted protease inhibitor. From 1998, NNRTI use dominated (56% in 1998, 74% in 2004 – 06), but by 2004 – 06, 20% of patients were taking therapy based upon a ritonavir-boosted protease inhibitor.

“We found that survival following HIV seroconversion has continued to improve over calendar time with a 97% reduction in the risk of death in 2004 – 2006 compared with the pre-1996 cohort”, write the investigators, “this is extremely encouraging and it remains to be seen how much further reduction in the risk of death is possible for infected individuals.” Concern is however expressed about the continuing high levels of late diagnosis in the UK, and the investigators conclude, “further provision of HIV testing should be encouraged so that diagnosis can be made as early as possible and therapy initiated when the full benefits can be realised.”