Symptomatic illness and low CD4 cell count at HIV seroconversion as markers of severe primary HIV infection.
BACKGROUND
The risk/benefit of initiating ART in primary HIV infection (PHI) is unclear. The benefits are more likely to outweigh the risks in patients with severe PHI. An accepted definition of severe PHI is, however, lacking.


METHODS
CASCADE patients with HIV test interval <6 months were classified as severe and non-severe PHI based on whether the following traits were recorded in the first 6 months following seroconversion: severe specific pre-defined symptoms, central nervous system-implicated illness, and ≥1, ≥2 CD4<350 (and <500) cells/mm(3). For each definition, we used Kaplan-Meier curves and Cox survival models to compare time to AIDS/death, censoring at the earlier of last clinic visit or 1/1/1997, when combination antiretroviral therapy (cART) became available.


RESULTS
Among 1108 included patients mostly males (85%) infected through sex between men (71%), 366 were diagnosed with AIDS/died. The risk of AIDS/death was significantly higher for individuals with severe symptoms, those with ≥1 CD4<350 cells/mm(3) or ≥2 CD4 <500 cells/mm(3) in the first 6 months [aHR (95% confidence interval) 2.1 (1.4,3.2), 2.0 (1.5,2.7), and 2.3, (1.5-3.5) respectively]. Median [interquantile range] survival for patients with ≥2, ≥1 and no CD4<350 cells/mm(3) within 6 months of seroconversion was 3.9 [2.7,6.5], 5.4 [4.5,8.4] and 8.1 [4.3,10.3] years, respectively. The diagnosis of CNS-implicated symptoms was rare and did not appear to be prognostic.


CONCLUSIONS
One CD4 count <350 or two <500 cells/mm(3) within 6 months of seroconversion and/or severe illness in PHI may be useful early indicators of individuals at high risk of disease progression.
Instituto de Salud Carlos III, Madrid, Spain.
Sara
S
Lodi
Martin
M
Fisher
Andrew
A
Phillips
Andrea
A
De Luca
Jade
J
Ghosn
Ruslan
R
Malyuta
Robert
R
Zangerle
Santiago
S
Moreno
Philippe
P
Vanhems
Faroudy
F
Boufassa
Marguerite
M
Guiguet
Kholoud
K
Porter
D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D018572:Disease-Free Survival; D005260:Female; D006679:HIV Seropositivity / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008297:Male; D008954:Models, Biological; D012720:Severity of Illness Index; D015996:Survival Rate
D015415:Biomarkers