Time from seroconversion to treatment in Europe and Africa

Simon Collins, HIV i-Base

People who are newly diagnosed with HIV, commonly expect to delay HAART for 5-8 years. However, the UK Register of Seroconverters has previously reported that at least a quarter of patients may need to start treatment within two years of infection. In a review of this cohort published in AIDS in January 2008, the median time from seroconversion to HAART initiation was 5.0 years but the IQR was 2.1 to > 10 years. The 25th percentile of time to starting HAART was 2.0, 2.0, 2.0 and 1.4 years in 1998-1999, 2000-2001, 2002-2003 and 2004-2006, respectively. [1]

This was also a conservative analysis as it excluded patients who started treatment within six months of infection due to complications during seroconversion. This analysis related to the period when UK guidelines recommended starting treatment before the CD4 count dropped below 200 cells/mm3.

At the IAS meeting, two studies from the CASCADE cohort of European seroconverters (which includes the UK data) provided further information on time to progression.

A European analysis, presented by Sara Lodi from the UK’s MRC, looked at time to CD4 counts dropping to below 500 cells/mm3, in order to inform policy should guidelines broaden to this higher threshold. [2]

Of over 11,700 adults (age >15 years) who seroconverted after 1992, over half (57%) reached CD4 <500 cells/mm3 during a median of 20 months (95%CI: 19.6, 20.5), with 29% censored at initiation of antiretroviral therapy. The proportion of patients with CD4 counts above 500 at 6, 12, 24 and 36 months after seroconversion was approximately 92%, 72%, 43% and 30%, respectively.

From these results, the authors concluded that 50% of patients would require treatment within 20 months of seroconversion, if future guidelines change the CD4 initiation threshold to 500 cells/mm3.

Increasing age at seroconversion was associated with faster progression (HR, 95%CI: 1.06,1.03-1.09 per 10-year increment). For example, 50% of the patients aged 15-20 still had counts >500 cells/mm3 after two years compared to only 35% of patients who were older than 40 at diagnosis. Unadjusted median times for those aged < 20, 20-29, 30-39, and 40+ years were 25.5, 21.9, 19.8 and 17.6 months, respectively.

No association was found with gender, transmission group and acute infection. Although numbers of patients with sub-type A, C and D were very low, there was an indication that progression may have been faster compared with sub-type B.

A second study from the CASCADE group, presented by Andrea de Luca, reinforced the finding that older age is associated with a shorter time to starting treatment, but also that older age was associated with better virological response (suppression to <50 copies/mL viral load). [3]

Of over 7100 patients who seroconverted after 1993 that were included in the analysis, just under half (48%) initiated antiretroviral treatment. Median time to starting treatment was 3.32, 3.15, 2.64 and 2.08 years for patients aged 15-29, 30-39, 40-49 and 50+ years respectively.

Later calendar period and seroconversion illness, but not age, were found to be independent predictors of CD4 count at ARV initiation. Increasing age was associated with better viral response (HR (95%CI)= 1.17 (1.06, 1.29); 1.30 (1.15, 1.47); and 1.25 (1.07, 1.47) for 30-39, 40-49 and 50+, respectively, compared to 15-29 year olds at seroconversion).

Data on progression rates in an African cohort were presented from the French ANRS 1220 Primo-CI cohort 1997-2008, in patients from Abidjan, C

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