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Can We Really Identify HIV-1 Long-Term Nonprogressors?
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Letter To The Editor
JAIDS Journal of Acquired Immune Deficiency Syndromes: Volume 37(1) 1 September 2004
Vento, Sandro MD*; Lanzafame, Massimiliano MD*; Malena, Marina MD†; Tositti, Giulia MD‡; Cainelli, Francesca MD*; Concia, Ercole MD*; Masiero, Giorgio MD§
*Section of Infectious Diseases
Department of Pathology
University of Verona
Verona, Italy
†Centre for Preventive Medicine
HIV Outpatient Clinic
ASL 20, Verona, Italy
‡Infectious Diseases Unit
S. Bortolo Hospital, Vicenza, Italy
§Infectious Diseases Unit
S. Maria della Misericordia Hospital
Rovigo, Italy
Since the early 1990s, numerous reports have described asymptomatic individuals whose CD4 cell counts remained higher than 500 cells/_L for longer than 10 years; they were defined as long-term asymptomatics, survivors, or nonprogressors (LTNPs). Their number is considered to be on the order of 2% to 10% of all HIV-1-infected subjects,4 but some of them might be slow progressors rather than real LTNPs. Because no virologic, immunologic, or genetic parameter is consistently able to predict those who will progress versus those who will not over a sufficiently long period of time, we have retrospectively reviewed the data of those individuals who were defined as LTNPs after 10 years of infection at 4 centers for HIV infection in Veneto (northeastern Italy) to determine how many continue to meet the definition nowadays.
We selected 31 (23 male and 8 female, median age = 39, range: 34-64 years) asymptomatic therapy-naive subjects who had been infected with HIV-1 (as demonstrated by the presence of anti-HIV antibodies in their serum) for at least 10 years and had a CD4 cell count higher than 500 cells/_L when first observed.
During a median follow-up of 67 months (range: 19-104 months), whereas 24 individuals continued to meet the definition of an LTNP, 7 subjects (29.5%, 1 female) no longer did so, having their CD4 count dropped to less than 500 cells/_L. Of these latter individuals, 3 started antiretroviral therapy, 1 developed Guillain-Barré syndrome, and 1 developed hepatitis C and alcohol-related cirrhosis with subsequent hepatocellular carcinoma. Of the 24 individuals still defined as LTNPs, only 1 was on antiretroviral therapy (which had been introduced because of a high viral load and not because of a CD4 cell count reduction).
Among the potential factors influencing (and eventually able to predict) progression of HIV-1 infection in our cohort, viral load seemed to be most important,5 because of 8 subjects with HIV RNA >5000 copies/mL at the first measure, 5 have progressed. Of the remaining 2 individuals with progressive HIV-1 disease, 1 subject had a viral load of 1911 copies/mL and HIV RNA had not been determined (the test was not available yet) in 1 subject when he met the definition of an LTNP. Age at infection, gender, CD8 cell number, CD4/CD8 ratio, intravenous drug use, sexual behavior, alcohol intake, smoking habits, and hepatitis B or C virus coinfections (data not shown) had no influence. Indeed, some of the oldest individuals surprisingly continue to be LTNPs.
Our results show that the definition of an LTNP is still elusive, because no factor can consistently predict whether an individual will maintain this status or not, and even a detectable viral load is not necessarily associated with progression of HIV-1 infection (although a level higher than 5000 copies/mL seems to be useful in predicting progression). In addition, in our cohort, we could not confirm the observations of Soriano et al,6 who found that a past history of intravenous drug addiction, male gender, and high alcohol intake were the variables statistically associated with LTNPs.
A more stringent definition needs to be used to predict nonprogression accurately, and the inclusion of HIV1 RNA values below detection seems to be mandatory.
Sandro Vento, MD*
Massimiliano Lanzafame, MD*
Marina Malena, MD†
Giulia Tositti, MD‡
Francesca Cainelli, MD*
Ercole Concia, MD*
Giorgio Masiero, MD§
*Section of Infectious Diseases, Department of Pathology, University of Verona, Verona, Italy
†Centre for Preventive Medicine, HIV Outpatient Clinic, ASL 20, Verona, Italy
‡Infectious Diseases Unit, S. Bortolo Hospital, Vicenza, Italy
§Infectious Diseases Unit, S. Maria della Misericordia Hospital, Rovigo, Italy
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