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The Body Covers: The 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy
Session 93.I: Late-Breaker Slide Session II

September 27, 1999

In the past year, a small Spanish study was presented which showed that lymph nodes taken from patients with undetectable viral loads on PI-containing HAART regimens had no evidence of viral activity and had restoration of normal-appearing lymph node architecture. This was compared to patients on a double nucleoside regimen who showed continued viral production and abnormal lymph node structure. This study has been used by some to argue that PIs had some special ability to restore lymph node function and were better for patients.

The current study, conducted by the NIH using patients from the Washington, D.C. practice of Doug Ward and others, studied 13 patients. 9 were ARV naive and were started on d4T, 3TC and efavirenz. 4 were on PI containing regimens. Lymph node biopsies were obtained at 8 months.

Interestingly, the NNRTI patients started with a mean plasma viral load of 384,375, while those on PIs began the study with a mean viral load of ~49,000 copies/ml.

In situ hybridization of the lymph nodes showed only 1 virus-producing cell in germinal centers in one sample from the efavirenz group and one from the PI group. 6/8 in the efavirenz group and 3/4 in the PI group showed no detectable plasma viral load at 8 months. NASBA studies showed replication-competent HIV at low levels in both groups -- 5/8 on the efavirenz arm and 2/3 on the PI arm had < 1 infectious unit per 106 cells.

Genotype and phenotype studies were also done, showing 4 patients with mutations that may reduce susceptibility to NNRTIs, 2 with A98W and 2 with K101Q. Neither of these is a common resistance mutation when patients are failing NNRTI therapy. Of note is that 2 of the 4 patients showing these mutations were in the PI-treated group and had never been exposed to NNRTIs. The authors are not sure of the significance of these mutations, and they may be polymorphisms.

This study seems to indicate that an undetectable viral load in the plasma by ultrasensitive testing, when obtained with a HAART regimen, translates into undetectable virus in the lymph nodes, regardless of whether a PI or efavirenz is used. This study was limited by not having baseline node biopsies. There was also no discussion of the impact on viral load architecture.

Further studies clearly need to be done with triple nucleosides, with the other PIs and NNRTIs and with new combinations of medications to see if one regimen does have a greater effect on restoration of lymph node structure and function than another.

Abstract: Evaluation of Lymph Node Viral Burden in HIV-Infected Individuals Receiving an Efavirenz-Based Protease Inhibitor-Sparing HAART Regimen
Authored by: M. Dybul, et al.

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