SUMMARY: HIV positive people who receive timely antiretroviral therapy (ART) before they experience significant immune deficiency may be able to reach a normal lifespan comparable to that of the HIV negative general population, suggest results from the Dutch ATHENA and European COHERE studies, presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last month in San Francisco. But not everyone necessarily benefits equally, with women having poorer prognosis.

By Liz Highleyman

ATHENA

ATHENA is a long-term national observational study that has been following HIV positive people in the Netherlands since the dawn of the combination ART era.

The current analysis included 4612 participants enrolled from 1998 through 2007 who had not yet started ART 24 weeks after HIV diagnosis. Patients who presented later in the course of infection and experienced an AIDS-defining event or who needed to start combination ART within 24 weeks were excluded.

Most participants (80%) were men, about 45% each were under age 35 or age 35-50, about 60% were from Western countries, 15% were from sub-Saharan Africa, and 20% from other countries. They had well preserved immune function with a median CD4 count of 480 cels/mm3.

Investigators compared progression to death in the cohort compared with the age- and sex-matched general Dutch population. ART initiation after 24 weeks was not explicitly captured in the model, but was assumed to have started according to treatment guidelines, which during the study period recommended therapy when CD4 count fell below 350 cells/mm3.

Results

	During 17,580 person-years of follow-up (average 3.3 years per person), 118 deaths occurred, for a mortality rate of 6.7 per 100 person-years.
	This compared with 35 deaths that would be expected in the matched HIV negative population.
	Predictors of death included:
	Older age at 24 weeks after diagnosis; CDC stage B disease at 24 weeks (symptomatic but no AIDS-defining conditions); Coming from somewhere other than Western countries or sub-Saharan Africa.
	CD4 count at 24 weeks did not predict prognosis, which the researchers suggested was due to the fact that 75% participants had counts > 350 cells/mm3, and increments above this level are associated with only minor improvements.
	The expected median number of remaining years of life at age was 25 was 52.7 for asymptomatic HIV positive people, similar to the 53.1 for the general population.
	Asymptomatic HIV positive men diagnosed at age 25 had a life expectancy
	0.4 years (5 months) less than uninfected men; this increased to 1.3 years lost by age 55 (1.5 years for women).
	Men with CDC stage B disease, in contrast, lost about 6 years of life at age 55, rising to about 7.5 years for women.

Based on these findings, the ATHENA researchers concluded, "The life expectancy of asymptomatic HIV-infected patients who are still treatment-naive and have not experienced a CDC-B or C event at 24 weeks after diagnosis approaches that of age- and gender- matched uninfected individuals."

However, they added, "follow-up time was short compared to the expected years lived," and predictions depend on the continuing success of ART.

COHERE

COHERE is a collaboration of 25 European observational cohorts of people who started combination ART for the first time in 1998 or later. The present analysis included 80,642 participants. Again, most (70% were men), the median age at ART initiation was 37 years, and the median CD4 cell count was 225 cells/mm3.

Investigators compared age- and sex-specific death rates in HIV positive adults after initiation of combination ART with those of the general population, and their relation to current CD4 cell count and time spent with a CD4 count > 500 cells/mm3. Follow-up time was categorized into 4 CD4 count strata: < 200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and > 500 cells/mm3.

The median duration of follow-up was 3.5 years. Standardized mortality ratios (SMR) were estimated with reference to age- and sex-specific mortality rates in country-specific general populations.

Results

	A total of 3813 deaths (2979 among men, 834 among women) occurred during the follow-up period, encompassing 315,340 person-years.
	Standardized mortality ratios varied according to current CD4 count:
	< 200 cells/mm3: SMR 13.0; 3.9 deaths per 100 person-years (4.2 for men, 3.0 for women); 200-349 cells/mm3: SMR 3.0; 0.8 deaths per 100 person-years (0.9 for men, 0.7 for women); 350-499 cells/mm3: SMR 1.8; 0.5 deaths per 100 person-years (0.6 for men, 0.4 for women); > 500 cells/mm3: SMR 1.5; 0.4 deaths per 100 person-years (0.4 for men, 0.2 for women).
	Death rates among men with CD4 counts > 500 cells/mm3 reached those of the matched general population after at least 3 years on ART spent above that threshold.
	SMRs for men were 1.4 after 1 year, 1.0 (indicating no difference) after 3 years, and 1.1 after 5 years.
	However, death rates among women with CD4 counts > 500 cells/mm3 remained higher than those of the general female population even after 5 years spent above this threshold.
	SMRs for women were 1.9 after 1 year, 1.7 after 3 years, and 2.4 after 5 years.
	For both men and women, there was less difference between HIV positive and general population life expectancy after excluding current or former injection drug users.

As expected, the researchers concluded, "mortality rates dropped, and were closer to those of the general population as the current CD4 cell count increased, reaching 0.4 per 100 person-years in those with a CD4 count > 500 cells."

"While HIV-infected men who were successfully treated reached similar mortality rates to those in the general male population after 3 years, this was not the case among women," they continued. "Though our results might be partly explained by other differences between HIV-infected and uninfected populations, they point to the importance of treatment adherence and early initiation of treatment."

ATHENA: Stichting HIV Monitoring, Amsterdam, Netherlands; Academic Med Ctr, Univ of Amsterdam, Netherlands; Onze Lieve Vrouwe Gasthius, Amsterdam, Netherlands; Imperial Coll Sch of Med, London, UK.

COHERE: INSERM, Bordeaux, France; Univ Bordeaux 2, France.

3/5/10

References

A van Sighem, L Gras, P Reiss, and others. Life Expectancy of Recently Diagnosed Asymptomatic HIV-infected Patients Approaches That of Uninfected Individuals. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 526).

C Lewden and the Mortality Working Group of COHERE. Time with CD4 Cell Count above 500 cells/mm3 Allows HIV-infected Men, but Not Women, to Reach Similar Mortality Rates to Those of the General Population: A 7-year Analysis.

C Lewden and the Mortality Working Group of COHERE. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 527).