The introduction of highly active antiretro-viral therapy (HAART) in 1997 dramatically changed the treatment of patients with human immunodeficiency virus (HIV) infection. Before HAART, the median survival after HIV seroconversion was approximately 12.5 years in patients 15 to 24 years of age and 7.9 years in those 45 to 54 years of age. Since HAART was introduced, several reports have documented striking improvements in survival and reductions in the progression to acquired immunodeficiency syndrome (AIDS). However, the overall picture remains unclear because of incomplete understanding of issues such as treatment failure, inadequate adherence to treatment, toxicity associated with HAART, and coinfections, especially with hepatitis C. The Concerted Action on Sero-Conversion to AIDS and Death in Europe (CASCADE) collaboration studied large cohorts of patients for whom reliable dates of seroconversion were available to assess the impact of HAART on progression to AIDS and survival and to identify risk factors for unsuccessful HAART treatment.

CASCADE investigators analyzed data from 22 cohorts including 7,740 people in Europe, Australia, and Canada. The risk of death or progression to AIDS was analyzed in terms of treatment, sex, age at seroconversion, exposure category, and acute presentation. Patients presenting before 1997 were compared with those who presented after the introduction of HAART. The proportion of person-time on HAART increased from 22 percent in 1997 to 57 percent in 2001.

Risk of progression to AIDS declined substantially: compared with the hazard ratio before 1997, the ratio was 0.46 in 1997 and 0.13 in 2001. The pattern of decline was a sudden initial drop in 1997 followed by moderate linear decreases every year thereafter.

Before 1997, age had a marked effect on prognosis, with more rapid progression in older patients. This effect has diminished since 1997; by 2001, there was little evidence of a difference in risk based on age. Before 1997, injection drug users had a lower risk of progression to AIDS than men infected sexually. After 1997, the risk of progression was higher in injection drug users than in other groups.

The decrease in the risk of death followed the same pattern as the decrease in disease progression. A sharp initial decline was followed by slower sustained annual reductions. The hazard ratio for death fell precipitously to 0.47 in 1997, and then to 0.16 in 2001. After 1997, mortality was higher among injection drug users than among other risk groups.

The authors conclude that HAART has had a significant impact on disease progression and mortality in HIV-infected patients, and that this treatment has altered the significance of age and exposure category. They speculate that poorer outcomes in injection drug users reflect reduced access to HAART or problems with compliance.

editor's note: The authors of this study point out that improvements in the rates of progression to AIDS and survival have been leveling off for several years, raising concerns about viral resistance, other causes of treatment failure, and enhanced vulnerability to other causes of mortality. They note the possibility that mortality could start to rise again.

Supporting patients during a lifetime of HAART requires special skills. Even if patients attend specialized clinics for HIV therapy, family physicians frequently are involved in the daily struggles that patients and their loved ones face in dealing with HIV infection. Some patients wear out and decide not to continue therapy. Others are overtaken by the disease or complications of treatments in spite of lives almost completely dedicated to medical regimens.

Although mortality rates have improved, HIV infection remains a burden on all concerned. One of the most terrifying comments I heard recently was from a young teenager who quipped that HIV infection now could be cured with pills. One of the saddest stories I have heard involved a woman in her 60s who was infected with HIV during a holiday romance. Can we use HAART to give hope to infected patients without encouraging recklessness in vulnerable patients of all ages?—a.d.w.