HIV-positive patients who take antiretroviral treatment reduce their mortality risk by 50%, an international team of investigators report in the January 2010 edition of AIDS. Especially substantial reductions in mortality risk were seen amongst those who started taking HIV treatment when their CD4 cell count was below 100 cells/mm3.
The study also showed the value of starting HIV treatment at higher CD4 cell counts. Patients with a CD4 cell count of 100 cells/mm 3 or below when they started HIV treatment were significantly more likely to die over five years than those who initiated antiretroviral therapy when their CD4 cell count was 500 cells/mm3 or above.
Study background
The introduction of effective, combination antiretroviral treatment in 1996 transformed the outlook for HIV-positive individuals. There is now a substantial corpus of research literature showing that therapy with anti-HIV drugs lowers viral load, increases CD4 cell count and extends AIDS-free survival.
However, non-HIV-related diseases are becoming an increasingly important cause of illness and death in patients with HIV. Therefore, it is important to understand the impact of HIV treatment on overall survival amongst individuals with the virus.
Earlier studies that have attempted to examine this issue have been limited by a number of factors.
Importantly, they have often lacked sufficient numbers of antiretroviral-naïve patients to accurately determine the effect of starting HIV treatment on all-cause mortality. Moreover, earlier research often did not take into account possible confounding factors such as baseline CD4 cell count and viral load and HIV transmission group.
Investigators from the HIV-CASUAL Collaboration therefore wished to gain a better understanding of the initiation of HIV treatment on the overall mortality risk for patients with HIV.
They studied the records of 62,760 patients who, between 1996 and 1998, were enrolled in twelve different cohort studies in Europe and the US. None of the patients had taken HIV treatment before their inclusion in these studies.
The investigators compared the mortality risk for patients who started treatment with those who did not. Mortality trends were also monitored over a five year period according to whether anti-HIV drugs were taken. The effect of baseline CD4 cell count and factors including HIV transmission group were also taken into account.
Results
HIV treatment was started by 26% of patients within the three months of entering a cohort study and by 55% of individuals by the end of follow-up (2003-2007).
The average duration of follow-up was 3.3 years.
A total of 2039 patients died, providing an overall mortality rate of 10 per 1000 person-years.
Overall, the risk of death from any cause was reduced by 52% for patients who started antiretroviral therapy.
Starting HIV treatment was especially beneficial for patients with a very weak immune system, the risk of death being reduced by 71% for those who initiated antiretroviral therapy when their CD4 cell count was below 100 cells/mm3.
Benefits were also apparent for individuals with CD4 cell counts that are considered “normal. Those who started HIV treatment when their CD4 cell count was 500 cells/mm3 or more had their risk of death from any cause reduced by 23% compared to those of a similar CD4 count who remained treatment-naïve.
Next, the researchers calculated the probability of surviving for five years for patients who initiated antiretroviral therapy and those who did not.
The overall survival probability was 96% for those who took treatment compared to 92% for those who did not.
Once again, these results varied according to CD4 cell count, with the greatest benefits seen for those with the weakest immune systems.
The five-year survival probability for those who started HIV treatment when their CD4 cell count was 100 cells/mm3 or below was 89% compared to only 43% for those with a CD4 cell count of this level who did not initiate antiretrovirals.
Starting HIV treatment also increased survival probabilities at higher CD4 cell counts. Patients who initiated therapy when their CD4 cell count was between 200 – 350 cells/mm3 were 6% more likely to be alive than those who did not (97% vs. 91%).
A slight survival benefit was also seen amongst patients who started taking antiretroviral drugs when their CD4 cell count was above 350 cells/mm3 (97% vs. 94%).
HIV risk group also affected the chances of survival even when HIV treatment was taken. Individuals who acquired HIV as a consequence of heterosexual sex, or through sex with another man were much more likely to be alive five years after starting antiretroviral therapy than those who acquired HIV through injecting drugs (97% vs. 97% vs. 83%).
“We estimated that combination antiretroviral therapy halved the mortality rate of HIV-infected individuals in developed countries, and that the absolute reduction in mortality was stronger for those with worse prognosis at the start of follow-up”, write the investigators.
However, they emphasise that such a finding does not argue for delays in starting HIV treatment.
Indeed they conclude that the five-year mortality risk of treated individuals with less than 100 cells/mm3 at baseline (11%) was almost four times greater than that of treated individuals with more than 500 cells/mm3 (3%).”
The HIV-CASUAL Collaboration. The effect of combined antiretroviral therapy overall mortality in HIV-infected individuals. AIDS 24: 123-37, 2010.