Newly HIV-infected have lower CD4s, higher viral loads compared to 1980s seroconverters

A large-scale analysis of 22 cohorts from Europe, Australia and Canada has found that, between 1985 and 2002, there has been a trend over time toward lower early CD4 cell counts and higher early viral loads shortly after seroconversion. The results were published in the online edition of The Journal of Infectious Diseases.

The central objective of this study, conducted by researchers in Rome and London, was to find whether there were shifts over calendar year in initial CD4 cell count and viral load measurements in people who had recently seroconverted. Little or no research has studied viral loads in this context, and studies of CD4 counts have found differing results. However, the recent Italian HIV Seroconversion Study (ISS), in results published in the journal AIDS in 2005, found a “modest, but statistically significant, decreasing trend of lower CD4 cell count [after seroconversion] in more recent years”, as did a Swiss cohort study published in 1999.

In the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) study, a research team (composed of many of the ISS researchers) brought together data from a large international collaboration of cohorts to see if the trends observed in ISS were true of a larger population, and to study the trends in viral load. Twenty-two European, Australian and Canadian cohorts were combined: to be included, participants had to have an HIV-seronegative test result followed by a positive one within one year: time of seroconversion was estimated as the midpoint between the two. Also, a CD4 count measurement and/or a viral load measurement had to be available within two years of the estimated seroconversion date and before the start of any antiretroviral therapy.

This resulted in two study groups: 3,687 for CD4 count analysis, and 1,584 for viral load. The analyses compared these figures for the 18 calendar years between 1985 and 2002; data were collected in December 2004.

CD4 cell analysis

An initial CD4 cell count was available for 3,687 seroconverters. The initial CD4 cell counts ranged between 6 and 3,020 cells/mm³ with an overall mean of 570 cells/mm³. There was a statistically significant decrease of initial post-seroconversion CD4 cell count of 6.33 cells/mm³/year (95% CI, 4.20 to 8.47) from 1985 to 2002 (this value actually increased slightly, to 6.61, when adjusted for possible confounders including sex, age, transmission route, and lag time in lab results).

Viral load analysis

An initial viral load measurement was available for 1,584 participants. The initial viral load ranged from 20 to 41,200,000 copies/ml with a median of 35,542 copies/ml. Viral load was estimated to increase by a mean of 0.044 log₁₀ copies/ml/year – an 11% annual increase (95% CI, 5% to 15%). (Analysis to allow for confounding factors only decreased the estimate slightly, to 0.035 log₁₀ copies/ml/year, or a 10% increase.)

Comparison with other studies

The researchers state that the conclusion regarding viral load is “an original finding, to our knowledge, for which no direct comparison with other studies is possible.” The finding of declining CD4 counts is in agreement with the previously mentioned Italian HIV-Seroconversion Study, and a Swiss cohort study published in 1999. However, several other previous studies found no evidence of a change in CD4 counts over time, including earlier studies (largely looking at the pre-HAART era) in Europe and the US, and a previously published paper (JAIDS 2003) from CASCADE itself. The 2003 CASCADE analysis included CD4 measurements taken after beginning antiretroviral therapy (nucleoside only), which may have skewed CD4 counts higher.

The researchers conclude that their results “suggest an effect of calendar year on early markers of disease progression”, that this may “point toward changes in … the circulating virus over time”, and that further cohort studies should ascertain “how repeatable and geographically widespread this finding is.”