Lopinavir/ritonavir monotherapy as maintenance treatment in HIV‐infected individuals with virological suppression: results from a pilot study in Brazil

Abstract

ObjectiveThe aim of the study was to evaluate the possibility of using lopinavir/ritonavir (LPV/RTV) alone as maintenance therapy in HIV-infected individuals with virological suppression. DesignThis was a single-armed single-centre pilot trial. MethodsAsymptomatic HIV-infected patients on highly active antiretroviral therapy (HAART) including LPV/RTV, and with plasma HIV RNA o40 copies/mL for at least 6 months, were enrolled in the study, during which they continued with LPV/RTV alone. The intention was to recruit 25 patients to be followed for 2 years. Viral failure was defined as two consecutive HIV RNA measurements 440 copies/mL. Nadir and baseline CD4 cell counts, highest ever HIV RNA load, time with undetectable viraemia before monotherapy, number of previous antiretroviral (ARV) regimens, and gene polymorphism at CYP3A4 and CYP3A5 were evaluated. ResultsAll patients (27) completed the study. Their median age was 43 years, and 66% were men. Ten patients (37%) failed to maintain virological suppression (the median time to HIV rebound was 10.5 months, with a range of 4-23 months). One patient developed full resistance to LPV and another developed neurocognitive impairment while on LPV/RTV which improved after HAART reintroduction. There were no differences between failures and nonfailures according to the analysed parameters. Patients with viral failure were successfully resuppressed. ConclusionsLPV/RTV maintenance therapy was associated with 37% failure, a higher than expected failure rate. In order to ensure that unnecessary risks are not being taken in patients on LPV/RTV, this finding should be further evaluated in large randomized trials for longer periods of follow-up.

Analysis of single-nucleotide polymorphisms (SNPs) in human CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs

“…Real Time PCR or restriction fragment length polymorphism (RFLP) were the most used, providing analyses of only defined and small CYP3A genomic areas, but lacked investigation of SNPs which are not yet described [4,18,19]. Hence, we developed a simple, inexpensive and reliable method based on classical qualitative PCR and subsequent sequencing of CYP3A (A4; A5), including all exons and part of the intron region (see Figure 1).…”

Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

“…Similarly, Brazilian schizophrenic patients with the CYP3A4*1A/1A genotype showed an increased risk to resisting a neuroleptic treatment [63] and, furthermore, patients with acute lymphoblastic leukemia with the same genotype had increased toxicity in response to chemotherapy, as observed for the mean rearrangement of Vγ/Jβ frequency during exposure [70]. However, despite the small sample size, no differences were observed according to the CYP3A4*1B polymorphism in the risk of treatment failure in HIV-infected patients from Porto Alegre under antiretroviral therapy [68], and similarly, CYP3A4*1B variant was not related to dose requirements of phenprocoumon in patients under oral anticoagulant treatment [60].…”

“…Additionally, no association was observed between CYP3A5*3 variant and antiretroviral therapy after two years of maintenance treatment with lopinavir/ritonavir [68] ( Table 2). …”

Simplification Strategies to Reduce Antiretroviral drug Exposure: Progress and Prospects

“…Overall 27 participants with ≥6 months of HIV-1 RNA levels <40 copies/ml were switched to lopinavir/ritonavir alone in a recent pilot study [52]. Prior virological failure on a PI-containing regimen was not exclusionary if genotype analysis identified ≤3 PI resistance mutations.…”