Identification of Severe Primary HIV Infection through Clinical, Immunological, and Virological Definitions
Sara Lodi*1,2, M Fisher3, A Phillips4, A De Luca5, J Ghosn6, R Malyuta7, R Zangerle8, S Moreno9, K Porter2, and CASCADE Collaboration in EuroCoord
1Inst de Salud Carlos III, Madrid, Spain; 2MRC Clin Trials Unit, London, UK; 3Brighton and Sussex Univ Hosp NHS Trust, Brighton, UK; 4Univ Coll London, UK; 5Univ Hosp of Siena, Italy; 6Univ Paris Descartes, France; 7Perinatal Prevention of AIDS Initiative, Odessa, Ukraine; 8Innsbruck Med Univ, Austria; and 9Hosp Ramon y Cajal, Madrid, Spain
Background: Treatment in primary HIV infection (PHI) is optional, but could be beneficial in patients with severe PHI. An accepted definition of severe PHI is lacking however. We aim to explore what clinical, immunological, and virological factors measured early in HIV infection best predict poor long-term prognosis.
Methods: CASCADE patients with interval <6 months between last negative and first positive HIV antibody test dates were classified as severe and non-severe PHI based on 3 definitions: clinical—symptomatic seroconversion (SC) illnesses with brain and neurological involvement; immunological—at least 1 CD4 <350 cells/mm3 in first 6 months; and virological—at least 1 HIV RNA>1 million copies/mL in first 6 months. For each definition, Kaplan-Meier curves and log-rank tests were used to compare survival (all-cause mortality) for severe and non-severe PHI with cART-naïve follow up ending at the earliest of death, last clinic visit, or 1 January 1997.
Results: Five thousand nine hundred and forty-six individuals with test interval <6 months had a median (IQR) age of 30 (35 to 36) years and CD4 count 551 (396 to 750) cells/mm3 at HIV SC. They were mostly males (79%), infected through sex between men (58%). Of 2019 individuals with test interval <6 months and information on SC illness, 98 (5%) had severe PHI based on the clinical definition. Median (IQR) survival time was 9 (7 to 15) and 10 (6 to 15) years for severe and non-severe, respectively. There was no significant difference in survival between patients with and without reported severe SC illness (p = 0.667). Among 3878 individuals with test interval <6 months and recorded CD4 count, 919 (24%) had severe PHI based on the immunological definition. There was strong evidence of difference in survival by severity of PHI (p <0.001) with median (IQR) survival times of 7 (5 to 10) and 13 (7 to -) years for severe and non-severe, respectively. Of 2334 individuals with test interval <6 months and at least one recorded HIV RNA within 6 months, 244 (10%) were classified as severe PHI according to the virological definition. Median (IQR) survival times were 8 (6 to 9) years for severe, lower than 9 (7 to -) years for non-severe PHI with no evidence of difference in survival between the two groups (p = 0.338).
Conclusions: A low initial CD4 cell count, rather than presence of severe clinical SC illness or high HIV RNA, may be a useful indicator for identifying patients who are likely to experience more rapid HIV disease progression.