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Tenofovir+Abacavir: is there a risk for K65R associated increased failure
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Reported by Jules Levin
There has been a concern that using tenofovir plus abacavir in combination could lead to an increased risk of viral failure since both drugs have a common resistance mutation, K65R. In theory, the concern might be heightened if used along with a NNRTI, or 3TC, FTC, or ddI. And in theory the concern would be reduced if TDF+ABC were used along with a boosted PI. Concern would also be reduced if a patient's viral load were undetectable before switching to a new regimen that included these two nukes, particularly if the new regimen included a boosted PI. If the new regimen was NNRTI-based along with TDF+ABC, concern would be heightened if viral load were detectable, less concerning if VL was undetectable but perhaps there would still be some concern if the regimen was NNRTI + TDF/ABC. If starting a new regimen the safest way to use TDF+ABC would be with a boosted PI. There were two posters at the Glasgow conference that provide some data which do not find higher viral failure rates when using TDF+ABC. But further research should be conducted to examine this question and to better characterize clinical situations.
Virological outcome of TDF plus ABC-based regimens in previously HIV suppressed patients (24wk preliminary results from recover study)
Maria J. Perez1, Jose A. Terron 2 , Antonio Antela 1 , Pere Domingo 3 , Esteve Ribera 4 , Antonio Ocampo 5 , Jose Hernandez 6 , Piedad Arazo 7 , Marisa Alvarez 8 , Santiago Moreno. 1Hospital Ramon y Cajal, Madrid, Spain; 2Hospital de Jerez, Andalucia, Spain; 3Hospital Sant Pau, Spain; 4Hospital Vall d Hebron, Barcelona, Spain; 5Hospital Xeral Cies, Vigo, Spain; 6Hospital San Cecilio, Granada, Spain; 7Hospital Miguel Servet, Zaragoza, Spain; 8Gilead Sciences, Madrid, Spain. Poster 308
To evaluate the efficacy of the TDF+ABC-based regimens in experienced patients.
We have conducted a switch study to identify the most frequent NRTI associated toxicities causing withdrawal from that drug. The responsible NRTI was switched, to TDF. We performed a bivariate, intent-to-treat analysis (ITT, NC=F) using as a dependent variable virological outcome (HIV-RNA< 200 copies/ml) at 12 and 24 wk.
We have available data of the first 101 patients with TDF+ABC based-regimens who have reached 24 wk in one of the following regiments: TDF + ABC+ NRTI (n=51), TDF + ABC + NNRTI (n=30), TDF + ABC + PIs (rtv boosted or not) (n=20). 87% were in their 3rd line of therapy or higher: all of them were previously suppressed patients when included in the Recover Study. After 24 wk, 90% of these patients remained suppressed. Virological success across the different combinations was: TDF + ABC + NRTI (84%) TDF + ABC + NNRTI (97%-only 1 failure, a non-adherent patient with NVP); TDF + ABC + PI (rtv boosted or not) (90%-only 2 failures due to non-adherence with LPV/r).ABC was used BID in all cases.
In heavily pretreated patients, TDF + ABC-based regimens showed lower efficacy with a third NRTI than a PI or NNRTI. In this study a significantly higher (94%) virologic success rate at 24 weeks with TDF + ABC-based regimens plus NNRTIs or PIs was observed.
Combination therapy with tenofovir and abacavir in clinical practice
Douglas J. Ward, John M. Curtin, Charles A. Owen. Dupont Circle Physicians Group, Washington, DC, USA. Poster 309
As demonstrated in ESS30009 the triple-nucleoside regimen of tenofovir (TFV), abacavir (ABC) and 3TC has an unacceptably high rate of virologic failure. The reason for the poor outcome with this apparently potent regimen is unexplained, and an adverse interaction between TFV and ABC has been hypothesized. Based on this, some have recommended avoiding this combination under any circumstances, although it has not been evaluated in regimens other than triple-nucleosides.
Retrospective review of a large clinical practice.
149 patients were identified who have been on TFV and ABC simultaneously. 74 of these were on a single additional drug: 7 on a third NRTI, 13 on efavirenz, 26 on nevirapine, 14 Kaletra, 7 atazanavir (6 unboosted), and 7 boosted amprenavir. All but one patient were treatment experienced. 18 began with elevated PCR's; 56 switched to this regimen while already undetectable. 27 take the ABC as 600 mg qd. After a median of 19 months 67 patients have PCR's <50, 4 are persistently low-grade positive and only 3 are virologic failures. Two patients with virologic failure on NNRTI regimens had only NNRTI mutations on genotype, with no NRTI mutations.
This observational analysis provides no evidence of a clinical negative interaction between TFV and ABC when not used as part of a triple-nucleoside regimen. Although controlled trials of this combination are needed, the combination of these two potent antivirals should not be too quickly discarded.
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