Reverse Transcriptase Inhibitors Nucleoside analogues (NRTIs) can be safely omitted from HIV salvage therapy, say the US researchers report inAnnals of Internal Medicine. The findings come from a randomized study between 2008 and 2011.
The study population consisted of patients with viral replication despite second- or third-line antiretroviral therapy. All patients were switched to an optimized scheme that included at least two active drugs. Half were randomly assigned to receive NRTIs, the other half to NRTI-sparing combinations. Results in 48 Week were similar in both arms of the study and schemes bias saver of NRTI were not lower than regimens containing NRTIs.
"This study demonstrated that the addition of NRTIs, the cornerstone of initial antiretroviral regimen can be omitted if a new scheme with optimized security that contains multiple antiretroviral drugs totally or partially active," was the comment of the authors. "This study contributes substantially to our knowledge of the optimum therapy for the treatment experienced patients".
Treatment guidelines recommend that patients with viral replication in progress, despite antiretroviral therapy, should be changed to a new system including at least two and preferably three fully active drugs. The standard of care includes NRTIs. However, patients are likely to have resistance to drugs of this class and is therefore questionable whether their addition has no benefits.
A team of researchers in the developments in the hypothesis formulated for the treatment of HIV - especially the introduction of new classes of drugs and agents that work against resistant viruses - mean NRTI may be omitted from safely rescue schemes. Consequently, the options engineered (or optimized treatment comprises omitting NRTI) study to test the theory.
Patients were recruited between 2008 and 2011 62 of clinics specializing in the care of people with HIV in the US. To be eligible, individuals were required to have experience with therapy scheme based on protease inhibitors and previous experience of, or resistance to reverse transcriptase inhibitors and reverse transcriptase inhibitors non-nucleoside analogue (NRTI and NNRTI). Each patient received an optimized salvage regimen that included at least two active drugs from the following classes: NNRTI driven protease inhibitors, integrase inhibitors, entry inhibitors (fusion).
Individual schemes were selected after surveying the historical treatment, considering resistance profile and tropism profile. Patients were then randomized to NRTI in addition to its optimized or omit NRTI combination.
The primary end point was the proportion of patients with treatment failure 48ª week (discontinuation of treatment in progress or viral replication). Data was also gathered on changes in CD4 counts, the emergence of new mutations resistance and safety.
A total of 360 patients were recruited and 337 (94%) completed the 48 weeks of follow-up. In both arms the most commonly assigned scheme was raltegravirIsentress () Plus ritonavir-enhanced,Prezista darunavir () AndIntelence etravirine () (56%). In that study arm was added NRTI 85% of participants added tenofovir and emtricitabine or lamivudine.
53 there were flaws in the limited NRTI regimen compared to 48 group arm that adds NRTIs. The cumulative probability of treatment failure at week was 48 29,8% for the omitted arm NRTI compared to 25,9% NRTIs provides for the patients. 3,2% difference between the two groups meant that the NRTI-sparing regimens were below the non-NRTI combinations add.
"The conclusion of non-inferiority was robust and consistent in sensitivity analyzes, the authors write.
Similar numbers of patients experienced virologic failure (versus 41 42) in the schemes to omit or add NRTIs. A viral load below 50 copies / ml was achieved by 64% of that in the group in which it omitted NRTI patients and 66% of subjects in braço.que provides NRTIs
The Increased CD4 counts were comparable between the two strategies and there were no differences in safety.
No deaths were observed in NRTI-sparing arm but the seven patients in Arm add-NRTI died. However, none of these deaths seemed to be related to treatment.
"The causes of death were similar to those reported in large studies of HIV cohort and could not be clearly attributed to NRTI toxicity," note the researchers. "The small number of events limited our ability to conclude that omit NRTIs leads to reduced mortality."
Patients participated in the experiment with an open layout with therapy and the authors acknowledge this as a limitation of their findings. They also acknowledge that the study may not apply to limited resources due to the high cost of the stress tests and tropism testing.
"In patients who have previously received antiretrovirals, NRTIs can be omitted from the new asset with security regimens since the activity of the cumulative regimen exceed the 2 fully active agents, the authors conclude. "The potential benefits to omit NRTIs include reducing charges per pill; reduced cost "and probably a decrease in toxicity associated with long-term NRTI."
Translated by Claudio Souza's original HIV salvage regimens can safely omit NRTIs, says US study Reviewed by Mara Macedo
Published: 04 2016 January
KT Tashima et al.HIV salvage therapy do not require similar inhibitors of reverse transcriptase. Ann Intern Med, 163: 908-17, 2015.