Decline in mortality rate amongst people with HIV has slowed in recent years

A study conducted by US investigators has found that although mortality has declined significantly in HIV-positive patients since the introduction of effective anti-HIV therapy, the rate of this decline has slowed in recent years. Their study, published in the October edition of AIDS also showed that noninfectious diseases, like heart and liver disease, are an increasingly important cause of death in HIV-positive patients.

Effective anti-HIV therapy became widely available in 1996 and brought about an immediate and dramatic fall in AIDS-related deaths. Improved treatment for opportunistic infections, the development of new antiretroviral drugs, and the evolution of HIV treatment guidelines have further contributed to falling mortality amongst HIV-infected patients.

Some recent studies have suggested that illnesses which are not normally considered HIV-related are an increasingly important cause of death in people with HIV. The side-effects of some anti-HIV drugs are also thought to be contributing to the overall burden of illness and death observed in HIV-infected patients.

Previous studies looking at mortality since the advent of effective anti-HIV treatments have often been limited either because they were restricted to a single site, had a small sample size, or only collected data for the period between 1996 and 2000.

Investigators from the US therefore analysed data provided by Adult/Adolescent Spectrum of HIV Disease (ASD) project. This project ran from 1992 to 2004. The investigators looked at the “perimortal” conditions (i.e. diagnosed conditions described on a death certificate or present at the time of death entered in medical records) occurring in HIV-positive patients in three distinct time periods: 1992 – 1995, the era before effective antiretroviral therapy; 1996 – 1999, the period of early potent HIV treatment; and 2000 – 2003, the era of contemporary anti-HIV treatment.

As well as using these data to track trends in mortality and causes of death, the investigators also analysed demographics, HIV transmission category, use of anti-HIV drugs, and CD4 cell counts to see if they could detect any changes in the characteristics of patients dying in the three periods of analysis.

Between 1992 and 2003, a total of 13,895 deaths occurred, but the investigators restricted their analysis to the 9,225 for which specific perimortal conditions were recorded.

Of these deaths, 5,407 (59%) occurred in the period before effective HIV therapy was available, 30% between 1996 and 1999, and 11% in the era of contemporary HIV treatment.

Over the three periods of analysis, the sex, race, and lowest CD4 cell count of patients who died changed significantly. The investigators noticed that patients dying were less likely to be male, less likely to be gay men, more likely to be black, more likely to be aged 55 or over, and more likely to have a lowest ever CD4 cell count of 100 cells/mm³ or above (all p

Between 1992 and 2003, the number of deaths caused by liver disease, viral hepatitis, high blood pressure, and alcohol increased significantly, whereas the mortality attributable to PCP pneumonia, nontuberculous mycobacterial disease and CMV all fell significantly.

The investigators then calculated that the standardised mortality rate dropped from a high of 488 per 1000 person years in 1995 to a low of 101 per 1000 person years in 2002. The annual mortality rate saw its sharpest drop during the early years of effective antiretroviral therapy (risk ratio [RR] 0.71; 95% CI, 0.69 – 0.97), with smaller falls seen in the period of contemporary anti-HIV treatment (RR: 0.93; 95% CI, 0.89 – 0.97).

Of the 36,000 patients entered in the ASD, 76% received anti-HIV therapy of any kind. Unsurprisingly, the proportion of patients receiving antiretroviral drugs increased sharply from approximately 60% in 1995 to approximately 80% in 1997.

“This analysis from a large cohort of HIV-infected patients in care during 1992 – 2003 demonstrated significant changes in the proportionate mortality of several perimortal conditions and a decline in annual mortality rates. Specifically, overall trends in proportionate mortality for many infections and AIDS-defining opportunistic infections decreased significantly”, comment the investigators.

However, the investigators noticed that infectious diseases were still an important cause of death in the most recent era. They believe that this was because of the “comparative youth of the cohort, since their deaths are less likely to be associated with chronic non-infectious diseases, which increase in prevalence among older populations.”

The investigators also comment upon the slowing of the decline in mortality in recent years. Although they write that “identifying the reasons for this are beyond the scope of this study” they suggest that it could be due to the late diagnosis of HIV in some patients, treatment side-effects, poor adherence and drug-resistant HIV.

Observed increases in mortality caused by diabetes, heart disease and high blood pressure could, the investigators believe, be due to the side-effects of anti-HIV therapy.