Starting HAART at CD4 above 350 does not give better T-cell response

Keith Alcorn
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This article is more than 22 years old.

Unless HIV treatment can be initiated within a year of infection, there is no evidence of an improved T-cell response to treatment started at CD4 counts above 350 cells/mm3 when compared treatment started at a CD4 count between 201 and 350 cells/mm3, according to an analysis of data from 20 seroconverter cohorts published in the March edition of the Journal of Acquired Immune Deficiency Syndromes.

The findings come from the Cascade collaborative analysis of data from 20 cohorts in which time of seroconversion has been pinpointed to within three years. 91% of individuals had an interval of less than two years between a negative and positive HIV antibody test.

Six hundred and eighty two treatment-naive seroconverters were identified, and classified as CD4 responders if they experienced a CD4 cell increase of greater than 100 cells/mm3 within six months of starting HAART.

Glossary

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

treatment-naive

A person who has never taken treatment for a condition.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

The median duration between seroconversion and initiation of HAART was three years; less than a quarter had an interval of greater than 6.3 years between seroconversion and HAART.

The median CD4 cell increase after 6 months was 119 cells/mm3. A slight trend towards poorer CD4 response with time from seroconversion was seen (OR 0.92 per 2 years (CI 0.86 – 0.98), p=0.00). However, after adjustment for age, gender, exposure category, history of prior treatment, CD4 nadir and prior AIDS diagnosis, a positive CD4 response was somewhat more likely in individuals who started HAART more than nine years after seroconversion (OR 1.77 (CI 1.00-3.15), and in individuals who started HAART less than one year after seroconversion (OR 1.50 (CI 1.07-2.10).

When the researchers compared response according to CD4 stratum, they found no significant difference in response according to whether treatment started in the bands 201-350, 351-500 or > 500 cells/mm3. Only amongst those with CD4 counts below 200 cells/mm3 was there a trend towards reduced response (0.72 (CI: 0.40-1.28).

Viral load before initiating HAART was predictive of CD4 response (OR=1.42 per 1 log10 copies/ml HIV RNA (CI: 1.21-1.65), p

The authors concluded that there was no advantage to starting HAART at a CD4 count between 350 and 500 compared to a CD4 count between 200 and 350 when considering the likelihood of experiencing a CD4 cell increase of at least 100 cells/mm3 after six months of treatment.

References

Cascade Collaboration. Short trem CD4 cell response after highly active antiretroviral therapy initiated at different times from seroconversion in 1500 seroconverters. JAIDS 32: 303-310, 2003.

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