SUMMARY: Less than 1% of people infected with HIV for 15 years did not experience disease progression in the absence of antiretroviral therapy (ART), according to findings from the CASCADE cohort reported at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. Even at 5 years after seroconversion, all but 10% progressed to the point of requiring treatment, and only 0.25% were considered HIV controllers with sustained undetectable viral load.

By Liz Highleyman

Jannie van der Helm and fellow investigators with the CASCADE Collaboration estimated progression-free survival among cohort participants with accurate dates of HIV seroconversion. Most prior studies of long-term non-progression (LTNP) used a cross-sectional (single point in time) approach and seroconversion dates were often uncertain.

CASCADE is an ongoing natural history study of HIV seroconverters from more than 2 dozen clinical cohorts in Europe, Australia, and Canada followed since the widespread adoption of combination ART in the late 1990s.

This analysis included 6506 participants who potentially had 10 or more years of follow-up based on their presumed seroconversion date. Data were collected through December 2008. Most (77%) were men, the average age at the time of seroconversion was 28 years, about half were men who have sex with men, and about one-quarter were injection drug users.

The researchers classified participants according to LTNP status, defined as being HIV positive without progression for at least 10 years following seroconversion. They then identified the likelihood of and factors associated with disease progression, defined as CD4 cell count falling below 500 cells/mm3, ART initiation, or an AIDS-defining event, whichever came first.

Results

	The estimated likelihood of survival without disease progression after seroconversion was:
	5 years: 9.5%; 10 years: 1.9%; 15 years 0.5%.
	The median time until progression was 1 year.
	10 years after presumed date of seroconverson, 189 participants (2.8%) were classified as long-term non-progressors.
	Within this group, 30 were women and the average age at seroconversion was 27 years.
	108 (57%) of these LTNPs, however, subsequently experienced disease progression within the next 3.5 years (i.e., a median 13.5 years after seroconversion).
	38% of the 10-year LTNPs were still non-progressors at 15 years and 14% were at 20 years.
	16 participants (0.25%) were considered HIV controllers, having 5 or more consecutive undetectable viral load measurements without treatment.
	In an analysis adjusting for multiple factors, independent predictors of progression (or loss of LTNP status) were:
	Female sex: hazard ratio (HR) 1.8, or nearly twice the risk; Lower CD4 cell count 10 years post-seroconversion (vs > 942 cells/mm3):   - 500-613 cells/mm3: HR 3.1; - 614-760 cells/mm3: HR 2.5; - 761-941 cells/mm3: HR 1.5. Higher viral load 10 years post-seroconversion: > 9725 vs < 400 copies/mL: HR 2.6.
	HIV transmission route and hepatitis C coinfection did not predict LTNP status.

Based on these findings, the investigators concluded that progression-free survival is uncommon, with "gradual but inexorable loss of LTNP status over time."

Even those participants with immunological and clinical control of HIV during the first 10 years after seroconversion seemed to lose this control rapidly thereafter, they added.

Studies of individuals with long-term non-progression and durable viral control, they suggested, might contribute to the development of preventive and therapeutic HIV vaccines.

Investigator affiliations: Health Service Amsterdam, Research, Amsterdam, Netherlands; MRC Clinical Trails Unit, London, UK; Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Service d'Epidémiologie et de Santé Publique, Université Paris, Paris, France; Royal Free & University College Medical School, London, UK; Robert Koch Institute, Berlin, Germany; Università degli Strudi di Milano H.S. Paolo, Milan, Italy.

8/20/10

Reference
J van der Helm, I Jansen, K Porter, and others (CASCADE Collaboration). The characterization of long-term non-progression of HIV-1 infection since seroconversion. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract TUAC0106.

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