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Severe Seroconversion Symptoms Predict Faster HIV Disease Progression


People who experience more severe symptoms or who have lower CD4 T-cell counts when they first become infected with HIV are more likely to experience faster disease progression later on, according to an international study described in the November 14, 2013, edition of PLoS Medicine.

A majority of people experience some flu-like symptoms when they first contract HIV, a period known as primary HIV infection. These may include fever, fatigue, sore throat, swollen lymph nodes, rash, and muscle or joint aches. This acute retroviral syndrome or seroconversion illness is generally mild, but some people experience more severe symptoms, such as thrush (oral candidiasis), indicating rapid immune suppression.

Sara Lodi from Instituto de Salud Carlos III in Madrid and fellow investigators with the CASCADE Collaboration looked at symptoms during primary HIV infection and their association with future disease progression.

The risks and benefits of starting antiretroviral therapy (ART) during primary HIV infection are not yet clear, the researchers noted as background. Some research suggest this may lead to lower viral load set-point and even viral suppression after stopping treatment in a small percentage of patients.

This retrospective analysis included 1108 CASCADE cohort participants infected with HIV for less than 6 months. Most (85%) were men and 71% were infected through sex between men; the median CD4 count during primary infection was 511 cells/mm3. Participants were classified as having severe or non-severe primary HIV infection based on whether they experienced specific pre-defined severe symptoms including thrush, bronchitis, and pneumonia, central nervous system symptoms, or CD4 counts <350 or <500 cells/mm3.

The researchers compared time to AIDS or death, with follow-up ending at either the last clinic visit or the beginning of 1997, when effective combination ART became generally available.


  • 127 participants (15%) were classified as having severe symptoms during primary HIV infection.
  • 54% of participants had CD4 counts <500 and 25% had <350 cells/mm3 during the first 6 months of infection.
  • 326 patients were diagnosed with AIDS and 40 died during follow-up, for an overall disease progression rate of 7.4 per 100 person-years.
  • After controlling for other factors, the risk of AIDS or death was significantly higher for individuals with severe seroconversion symptoms (adjusted hazard ratio [HR] 2.1, or about twice the risk).
  • The risk was also higher for people with at least 1 CD4 count <350 cells/mm3 or at least 2 measurements <500 cells/mm3 during the first 6 months after infection (adjusted HR 2.0 and 2.3, respectively).
  • People with both severe primary infection symptoms and low CD4 cell counts had double the risk of progression to AIDS or death compared to those with severe symptoms alone
  • Median AIDS-free survival duration was significantly shorter for people with severe primary infection symptoms (6.3 vs 8.3 years, respectively).
  • Median survival duration for patients with at least 2, at least 1, and no CD4 counts <350 cells/mm3 within 6 months of seroconversion was 3.9, 5.4, and 8.1 years, respectively.
  • Diagnosis of central nervous system symptoms was rare and did not appear to be prognostic.

"One CD4 count <350 or two <500 cells/mm3 within 6 months of seroconversion and/or severe illness in primary HIV infection may be useful early indicators of individuals at high risk of disease progression," the researchers concluded.

Based on these findings, they suggested that people with severe symptoms during primary infection may benefit from starting antiretroviral treatment promptly.



S Lodi, M Fisher, A Phillips, et al (CASCADE Collaboration). Symptomatic Illness and Low CD4 Cell Count at HIV Seroconversion as Markers of Severe Primary Infection. PLoS ONE 8(11):e78642. November 14, 2013.