NNRTI-based HAART associated with quicker CD4 cell gains than PI-based therapy

Michael Carter
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This article is more than 21 years old.

Taking a non-nucleoside (NNRTI) results in a slightly quicker rise in CD4 cell count than taking a protease inhibitor (PI), according to an observational Canadian study published in the November 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The Canadian investigators also established that CD4 cell count increased more rapidly amongst patients taking NNRTIs than PIs even if they had a CD4 cell count below 200 cells/mm3.

It has been suggested that protease inhibitors have an impact on CD4 cell gain independent of their virologic effect. With this in mind, investigators in British Columbia wished to evaluate CD4 cell response in patients starting HAART between 1996 and 2000. Follow-up was provided until March 2002, and the study end-point was the first of two CD4 cell counts showing an increase of at least 50 cells/mm3 over baseline.

A total of 1,522 patients were included in the study. Of these, 439 (31%) started a HAART regimen which included an NNRTI, which in nearly all cases was nevirapine (413 individuals, 94%). The majority of individuals were prescribed a single PI (983, 69%), and 100 patients (6.6%) took dual-PI therapy.

Glossary

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

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. 

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Individuals initially prescribed NNRTI-containing therapy had more rapid CD4 cell gain (p=0.005). This remained the case after adjusting for variables including a history of injecting drug use, age, sex, viral load, baseline CD4 cell count, and viral load, 95% adherence, and whether HAART was started before or after July 1997 (RH, 1.23, 95% CI, 1.09 – 1.41, p=0.002).

Investigators repeated their analysis looking specifically at CD4 cell response amongst the 597 patients who started HAART with a CD4 cell count below 200 cells/mm3, the group of patients who most need a rapid increase in their CD4 cell count when starting HIV therapy. They found that even when all the other variables listed above were included in their analysis, patients taking an NNRTI were significantly more likely to achieve the first of two CD4 cell counts above 200 cells/mm3 than individuals taking a protease inhibitor (RH 1.27, 95% CI, 0.97 – 1.67, p=0.080).

The investigators caution that their results were obtained from an observational, non-randomised study, however “despite these limitations…we believe that these results should make a contribution to the question of differential CD4 cell count responses associated with PI- and NNRTI-based HAART and indicates the rather comparable effects on NNRTIs and PIs on CD4 cell count responses.”

Data from the same investigators will appear in a forthcoming issue of AIDS showing that NNRTI-based HAART has similar virological efficacy as HAART that includes a PI.

Further information on this website

CD4 and viral load - booklet in the information for HIV-positive people series

Treatment guidelines of the British HIV Association

References

Wood E et al. CD4 cell response to nonnucleoside reverse transcriptase inhibitor or protease inhibitor-based highly active antiretroviral therapy in an observational cohort. JAIDS 34: 347 – 348, 2003.

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