Response to HAART improves due to better drugs and more expertise in their use

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Between 1996 and 2002 there was a significant improvement in the proportion of patients starting highly active antiretroviral therapy (HAART) who achieved suppression of HIV and an increase in their CD4 cell count, according to data from Johns Hopkins University published in the June 1st edition of The Journal of Acquired Immune Deficiency Syndromes.

The investigators found that the use of a non-nucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor rather than an unboosted protease inhibitor was associated with an improved virological outcome. They also found that calendar year was independently associated with HIV suppression, suggesting, “unmeasured factors…such as adherence support, are likely to be contributing to improved HIV suppression.”

Observational studies soon after the introduction of HAART indicated that as few as 50% of patients had virological suppression after six months of treatment. Investigators from Johns Hopkins University in Baltimore wished to see how virological response to HAART had changed in clinical practice since 1996.

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

virologic response

Reduction in viral replication in response to treatment, especially achievement of an undetectable viral load.

 

Data were analysed for patients who started HAART from 1996 to 2002. The investigators assessed the proportion of patients who had a viral load below 400 copies/ml six months and twelve months after starting HAART. A subset analysis was performed including only patients who were antiretroviral naïve when they started HAART.

In addition, investigators assessed changes in CD4 cell count at six and twelve months, treatment changes and the incidence of new AIDS-defining illnesses.

Virologic response improves

Over time there was a significant improvement in the proportion of patients with a viral load below 400 copies/ml. After six months of HAART, 43% of patients in 1996 had a viral load below 400 copies/ml, increasing to 72% in 2001-2002. In 1996, 60% of patients had a viral load below 400 copies/ml after a year of HAART, but by 2001-02, 80% of patients had achieved this endpoint a year of HAART.

Of the patients who were naïve to antiretroviral therapy at baseline, 59% had a viral load below 400 copies/ml after six months in 1996 compared to 74% in 2001-02. After a year of treatment, 72% had viral suppression below 400 copies/ml in 1996 with 78% achieving this in 2001-02.

CD4 cell count improves as well

Increases in CD4 cell count ranged from 67 cells/mm3 (1996) to 99 cells/mm3 (2002) after six months and 116 cells/mm3 (1996) to 142 cells/mm3 (2002) after a year of treatment.

The rate of new opportunistic infections declined from 14% in 1996 to 10% in 2001-02.

In multivariate analysis, HIV suppression at six months was significantly associated with the use of a boosted protease inhibitor or NNRTI rather than an unboosted protease inhibitor, a lower baseline viral load and a higher baseline CD4 cell count. The investigators repeated their analysis, adjusting for these variables and found that calendar year was still associated with virological outcome.”

“We believe that these results reflect improvements in therapy and expertise in using that therapy”, conclude the investigators.

References

Moore RD et al. An improvement in virologic response to highly active antiretroviral therapy in clinical practice from 1996 through 2002. J Acquir Immune Defic Syndr 39 (2): 195 – 198, 2005.