Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Tenofovir disoproxil fumarate (TDF), the first approved nucleotide analog (NtRTI), has shown a potent antiviral effect (mean reduction in plasma HIVRNA of 0.6 logs in pretreated patients) in clinical trials. TDF potency seems to be compromised when nucleoside-associated mutations (NAMs) are present, particularly 41L and/or 210W.

In order to assess the efficacy of TDF, all patients (pts) included in the Spanish expanded access program in 7 hospitals who have completed 12 and 24 weeks of follow-up were examined. All subjects were on virological failure after receiving regimens including all 3 drug families.

A total of 139 pts were included. Mean age was 40 years; male 78%. Mean time on HAART before beginning TDF was 84 months (mo). Up to 60% of pts added new concomitant drug(s) (PI in 85%) to the salvage regimen with TDF. At baseline, mean plasma HIV-RNA was 3.9 logs and mean CD4 count was 313 cells/¦Ìl. At 3 mo, mean drop in HIV-RNA (logs) was -1.03, and mean increase in CD4 (cells/¦Ìl) was +51. At 6 mo (n=68), these figures were -0.79 and +28, respectively. Virologic response (≥1 log drop or HIV-RNA <50 copies/ml) was achieved in 54% of pts at 3 mo and 46% at 6 mo. According to baseline genotype, mean change in plasma HIV-RNA at 3 mo was -1.17 logs for pts with <3NAMs and -0.82 logs for those with ≥3 NAMs (p=0.13). Overall, virologic response (logs) in pts with M41L was on average - 0.57 but increased to -1.34 when this mutation was absent (p=0.001). Changes in HIV-RNA according to NAMs and M41L mutation are shown in table:

Concomitant use of a new PI achieved a HIV-RNA drop of -1.39 logs, compared to -0.53 logs when a new PI was not added (p<0.001). At 6 mo, the different response according to M41L observed at 3 mo was not found. In the multivariate analysis, only the concomitant use of a new PI (positive effect) and the presence of the M41L mutation (negative effect) were signifi- cantly associated with a better virologic response. However, this association was not found at 6 mo follow-up.

TDF-based salvage regimens provide a significant virologic response, that in our study is higher than expected. This may be explained by the high proportion of patients who were added a new PI. The short-term mean drop in plasma HIV-RNA was significantly higher in subjects lacking the M41L mutation.

Download Conferences Abstracts

1 Service of Infectious Diseases, Instituto de Salud Carlos III, Madrid.

2 Infectious Diseases Unit, Hospital de Sant Pau, Barcelona.

3 Hospital Clínico de Valencia.

4 Hospital Virgen de la Macarena, Sevilla.

5 Hospital Clínico de Madrid.

6 Mutua de Tarrassa, Barcelona.

7 Hospital Central de Asturias, Oviedo, Spain.

2002-11-17
P2

Copyright © 2002 - The Gardiner-Caldwell Group, Ltd.. All Rights Reserved. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Sixth International Congress on Drug Therapy in HIV Infection, c/o The Gardiner-Caldwell Group Ltd, part of The Thomson Corporation, Peakside House, Alder Court, Tytherington Business Park, Tytherington, Cheshire SK10 2XG, UK - Tel: +44 (0)1625 668000, Fax: +44 (0)1625 668121 Email: hiv6@gardiner-caldwell.com

This information is designed to support, not replace, the relationship that exists between you and your doctor. ©1980, 2005. AEGiS.