HAART patients at greater risk of severe side-effects than AIDS

Michael Carter
Published: 02 December 2003

HIV-positive individuals who take HAART are more likely to experience a serious or life-threatening treatment side-effect than develop an AIDS-defining condition, according to a US study published in the December 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The study investigators suggest that doctors should carefully assess their patients’ medical history and circumstances before prescribing anti-HIV therapy so they can avoid the use of drugs that could aggravate existing health conditions.

Investigators analysed the results from five US multi-centre HAART trials that had a common system of reporting adverse events, AIDS events and deaths between 1996 and 2001. Partial findings from the study were presented at the Ninth Conference on Retroviruses and Opportunistic Infections in 2002.

The investigators wished to establish the incidence and determinants of serious or life-threatening treatment side-effects, AIDS-defining illnesses and death.

Data were analysed from 2,947 patients who were followed for a median of 20.7 months, contributing 5,940 person-years of follow-up. At the time of enrollment to the studies, 53% of individuals were antiretroviral naïve, average age was a little over 39 years, 83% were male, 55% were gay men, 16% had a history of injecting drug use, the median CD4 cell count was 211 cells/mm3, and 40% had a previous AIDS diagnosis.

All the patients were prescribed anti-HIV therapy, and at the twelfth month of follow-up 89% were receiving HAART (70% a protease inhibitor and 19% a non-nucleoside-based regimen), 3% mono- or dual-nucleoside analogue treatment, and 8% had stopped anti-HIV treatment on either a permanent or temporary basis.

A severe or life threatening side-effect (grade 4 adverse-event) was experienced by 675 individuals (11.4 cases per 100 person years), 332 developed an AIDS-defining condition (5.6 cases per 100 person years), and 272 people died (4.6 cases per 100 person years).

The cumulative percentage of patients with a severe or life threatening side-effect at month twelve was 15.6%, at month 24, 23.7% and at month 36, 30.8%. The corresponding percentages for AIDS events were 7.3%, 10.8%, 16.5%, and the percentages for deaths were 3/9%, 7.9% and 13.1%.

Liver-related side-effects were the most frequently reported adverse events (148 patients, 2.6 per 100 person years).

When the investigators looked at the risk factors for the experience of severe or life-threatening side-effects, they found that the risk was lower in younger patients (hazard ratio [HR] 0.83 for every decade in years, p=0.0001), and patients who had never taken anti-HIV drugs before (HR=0.59, p=0.0001). The risks were increased for individuals with a history of injecting drug use (HR=1.41, p=0.0006), lower baseline CD4 cell count (for every 100 cells/mm3, HR=1.06, p=0.04), and a prior AIDS-defining illness (HR=1.22, p=0.03).

The investigators also found that women were at increased risk of experiencing severe or life-threatening neutropenia (HR= 1.76, p=0.03), whilst African Americans were at increased risk of neutropenia (HR=3.78, p=0.0001), anaemia (HR=2.46, p=0.008), and kidney-related events (HR=22.41, p=0.00250. People of Latino origin had an increased risk of neutropenia (HR=2.75, p=0.01).

Of the 272 people who died, 159 experienced both a grade 4 adverse reaction and an AIDS-defining illness.

Coinfection with hepatitis B (HR=5.97, p=0.0001) and hepatitis C (HR=2.74, p=0.009) were significantly associated with the risk of experiencing a severe liver-related side-effect.

The investigators note, “our principal finding is that the rate of grade 4 events is greater than the rate of AIDS events, and that the risk of death associated with these grade 4 events was very high for many events.”

They believe that their study has two important implications. Firstly, the procedure for collecting data of adverse events during clinical trials needs to be improved. Secondly, doctors need to carefully assess their patients for the existence of other medical problems, taking into account social and economic status and drug and alcohol use. “For example, patients at increased risk of cardiovascular events might benefit from being placed on a protease inhibitor-sparing HAART regimen. Similarly, patients with a history of severe depression may be better off with an efavirenz-sparing HAART regimen.”

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Reisler RB et al. Grade 4 events are as important as AIDS events in the era of HAART. JAIDS 34: 379 – 386, 2003.

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