Virological efficacy of PI monotherapy for HIV-1 in clinical practice

Abstract

BackgroundClinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied.MethodsAn observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation.ResultsNinety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes.ConclusionsThere was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation.

HIV Cerebrospinal Fluid Escape and Neurocognitive Pathology in the Era of Combined Antiretroviral Therapy: What Lies Beneath the Tip of the Iceberg in Sub-Saharan Africa?

“…The interpretation of the association between CSF escape/discordance and bPI is unclear, as the rationale for bPI monotherapy use in select patients may be a confounder. Patients who are given bPI monotherapy may be poorly-adherent and bPI is used due to its high barrier to resistance [ 59 ] or may be ill patients and bPI monotherapy is used in order to minimise drug interactions [ 60 ] or may have experienced toxicity from NRTIs and bPI is used as a temporary measure [ 61 ]. Boosted PI-based therapy may represent poor adherence, extensive ART experience and the opportunity for the virus to have evolved under drug pressure.…”

Long-term use of darunavir/ritonavir-containing regimens in daily practice in Belgium: retrospective observational cohort data of 1701 HIV-patients

“…The MONET [21], MONOI [25], PROTEA [20] and PIVOT [26] trials have shown that DRV/r monotherapy can be considered as a treatment option for patients with stable virological suppression on combination therapy (HIV-1 RNA <50 copies/mL for at least six months). DRV/r monotherapy has also recently been reported to exhibit a good efficacy and safety profile in routine clinical practice [14,15,27]. In this cohort, DRV/r QD monotherapy was well tolerated, adverse events were mainly GI related as observed in the MONET and PROTEA monotherapy trials [20,28] as well as in another real world study from Spain [14].…”

Current antiretroviral therapies and future trends in management of HIV-1 infection

“…Concerns persist about virologic escape in the CSF and the development of CNS disease in subjects receiving PI monotherapy, and this combination is not recommended in HBV coinfection. In addition, real-world studies report a higher incidence of virological failure and emergent resistance than has been described in clinical trials (16).…”