Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can be omitted safely from HIV rescue therapy, say report researchers from the United States Annals of Internal Medicine. The results come from a randomized study conducted between 2008 and 2011.
The study population consisted of patients with viral replication despite the second or third line of antiretroviral therapy. All patients were switched to an optimized regimen that included at least two active drugs. Half were randomized to receive NRTIs, the other half to combination NNRTIs. Results at week 48 were similar in both arms of the study and the regimens of bias saver of NRTIs were not inferior to therapeutic regimens containing NRTIs.
"This study demonstrated that the addition of NRTIs, the cornerstone of the initial antiretroviral regimen, can be omitted if a new, optimally safe regimen containing multiple or fully active antiretroviral drugs is the author's comment. "This study contributes substantially to our knowledge of the optimal therapy for the treatment of experienced patients."
Treatment guidelines recommend that patients with ongoing viral replication, despite antiretroviral therapy, should be switched to a new regimen that includes at least two and preferably three fully active drugs. The standard of care includes NRTIs. However, patients are likely to have drug resistance of this class and therefore it is questionable whether their addition has any benefits.
A team of researchers in which developments in the hypothesis formulated for HIV treatment - especially the introduction of new classes of drugs and agents working against resistant viruses - would mean that NRTIs can be omitted from safe rescue schemes. Therefore, the options (optimized treatment that includes or omit NRTIs) from the study to test their theory.
Patients were recruited between 2008 and 2011 from 62 outpatient clinics specializing in providing care to people with HIV in the United States. To be eligible, subjects were required to have experience with a protease inhibitor-based therapy regimen and previous experience of, or resistance to, reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). Each patient received an optimized rescue regimen that included at least two active drugs from the following classes: NNRTI, driven by protease inhibitors, integrase inhibitors, inhibitors of entry (fusion).
Individual regimens were selected after a history of treatment, considering resistance profile and tropism profile. Patients were then randomized to receive NRTI in addition to their optimized combination or omit NRTI.
The primary endpoint of the study was the proportion of patients failing treatment at 48th Week (discontinuation of ongoing treatment or viral replication). Data were also collected in the CD4 count changes, the appearance 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 attributed regimen was raltegravirIsentress () plus ritonavir-enhanced, Prezista darunavir () is Intelence etravirine () (56%). In the study arm where ITRN 85 was added% of participants added tenofovir and emtricitabine or lamivudine.
There were 53 failures in the limited ITRN scheme when compared to the 48 group in the arm where ITRN is added. The cumulative probability of treatment failure at week 48 was of 29,8% for the arm that omitted the NRTI compared to 25,9% for the NRTI provides the patients. 3,2% difference between the two groups meant that the sparing of NRTI regimens were lower than non-add-NRTI combinations.
"The non-inferiority finding was robust and consistent in sensitivity analyzes, write the authors.
Similar numbers of patients experienced viral failure (41 versus 42) in omitting or adding NRTI schemes. A viral load below 50 copies / ml was achieved by 64% of that in the group where omitted NNRTI patients and 66% of individuals in the arm. Which provides the NNRTI
The increase in CD4 counts were comparable between the two strategies and there were no differences in safety.
No deaths were observed in the NRTI sparer arm but seven patients in the add-NRTI arm died. However, none of these deaths appeared to be treatment-related.
"The causes of death were similar to those described in large cohort studies of HIV and could not be clearly attributed to NRTIs," the researchers note. "The small number of events limited to our ability to conclude that omitting NRTIs leads to reduced mortality."
Patients participated in the experiment with an open scheme with therapy and the authors recognize this as a limitation of their findings. They also acknowledge that the study may not be applicable to limited resources due to the high cost of resistance testing and tropism testing.
"In patients who have previously received antiretroviral drugs, NRTIs may be omitted from the new active with safety of therapeutic regimens provided that the cumulative therapeutic regimen activity exceeds that of 2 fully active agents, the authors conclude. "The potential benefits of omitting NRTI include reducing pill charges; reduced cost "and probably a decrease in long-term toxicity associated with NRTIs."
Translated by Claudio Souza's original HIV salvage regimens can safely omit NRTIs, says US study Reviewed by Mara Macedo
Posted in: 04 January of 2016
Tashima KT et al. HIV salvage therapy does not require analogue reverse transcriptase inhibitors.. Ann Intern Med, 163: 908-17, 2015.