Less than half of deaths at London HIV clinic due to AIDS since 1998

The annual mortality rate amongst patients attending one of the United Kingdom’s main HIV treatment centres fell by half between 1998 and 2003, according to a study published in the January 2 edition of AIDS. Doctors at the Royal Free Hospital also found that less than half of the deaths that occurred in their patients were AIDS-related and that there were several other notable causes of death.

“While mortality rates among HIV-infected individuals at our centre have fallen since 1988”, they write, “the deaths that do now occur are more diverse and are the result of a number of factors.” These include late presentation, delayed use of potent antiretroviral therapy, previous use of treatment combinations that would now be considered suboptimal, and resistance to anti-HIV drugs.

Effective antiretroviral therapy has dramatically cut illness and death amongst HIV-positive individuals, but between 200 and 400 patients die with HIV in the UK each year. The Royal Free doctors conducted an analysis of their database to see just how many of their patients had died since the use of potent combinations of antiretroviral drugs became widespread at their centre in 1998 and to see if any of these deaths could have been avoided.

Between early 1998 and the end of 2003 a total of 121 deaths were recorded amongst HIV-positive patients treated at the hospital. The death rate fell from 2 per 100 person years between 1998 and 2000 to 1 per 100 person years between 2000 and 2003.

AIDS (46%) was the single greatest cause of death, 22% of deaths were due to unknown causes, and 4% were attributed to the side-effects of anti-HIV therapy. Other studies have suggested an increase in liver-related mortality and cardiovascular disease in HIV-positive patients since potent antiretroviral therapy was introduced and the investigators found that 3% of deaths were attributable to hepatitis B or hepatitis C virus infection and 3% to cardiovascular disease. Other known causes unconnected to HIV infection accounted for the remaining 28% of deaths.

Antiretroviral therapy had been taken by almost three-quarters of individuals prior to death and 74 (62%) had taken a combination of potent antiretroviral drugs. The median duration of combination antiretroviral therapy prior to death in 1998 was 18 months, this increased to a little over three and a half years by the end of 2003.

Amongst patients who took potent combination anti-HIV therapy prior to death, 40% had started anti-HIV treatment before effective treatment was available. Only 10% of individuals who took combination antiretroviral therapy before death started this therapy less than three months before their death.

Patients who received potent antiretroviral therapy were highly treatment-experienced and had taken a median of seven individual drugs by the time they died, and 53% had taken drugs from the three main classes of antiretrovirals. The investigators noted that CD4 cell count fell from a median pretreatment level of 128 cells/mm³ to 68 cells/mm³ at the time of death, and that almost a third of patients who took combination therapy had a viral load below 400 copies/ml at the time of their death.

Anti-HIV therapy was stopped by almost two-thirds of patients an average of nine months prior to their death. A total of 47 patients died without ever taking antiretroviral therapy. These treatment-naive patients had a median CD4 cell count at the time of death of 167 cells/mm³ and 10% had a viral load below 400 copies/ml.

The investigators then looked at the 64 deaths which had occurred in patients who had taken at least six months of potent combination antiretroviral therapy. Median CD4 cell count at the time of death was 28 cells/mm³. Half of these deaths were HIV-related and 30% occurred in patients who had a viral load below 400 copies/ml at the time of death. The median number of anti-HIV drugs used by these patients was five. Three patients died of lymphoma and other deaths were due to malignancies and infections characteristic of late-stage HIV infection including disseminated Kaposi’s sarcoma and CMV.

A rebound in viral load after starting treatment was seen in 44 patients. Resistance tests were performed on 26 of these individuals, and it was found that 19 (73%) had at least one major resistance mutation.

Other tests revealed that patients who died had low haemoglobin (p = 0.009) and low albumin (p = 0.02).

The investigators comment that their findings further demonstrate the importance of “early diagnosis and timely initiation of” effective antiretroviral therapy.