Central Nervous System HIV Infection in “Less-Drug Regimen” Antiretroviral Therapy Simplification Strategies

Abstract

Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.

High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial

“…LPV/r monotherapy is one of the best known options of tailored therapeutic approaches for patients with persistently suppressed HIV viremia in which fewer than the recommended standard of three antiretrovirals are used [ 4 ]. The primary objective of this study was to measure the effect on HIV patients’ quality of life of simplifying conventional TT with an MT regimen.…”

“…During the last decade, the use of simplification regimens [ 4 ], initiated once the patient has become stable and virologically suppressed, has become more attractive. Putative advantages of monotherapy (MT) strategies include decreases in toxicity, antiretroviral interactions, treatment complexity and cost, as well as preserving future treatment options, as the PIVOT study has recently shown [ 5 ].…”

HIV-1 and Compromised Adult Neurogenesis: Emerging Evidence for a New Paradigm of HAND Persistence

“…Given these interesting findings, strategies involving the switching and simplification of ART regimens (one or less NRTIs, totaling < 3 drugs) have been extensively explored to mitigate drug-induced toxicity, viral resistance, and adherence interruption 35–39 . However, the benefits of simplified ART regimens remain controversial because they may be less effective in suppressing CNS viral loads and improving neurological function 40–42 . A long-term three-decade retrospective study using a large cohort of 4992 HIV-positive patients with regimen switching protocols demonstrated that neurocognitive deficits do not necessarily improve in most cases, even if systemic viral suppression is successfully achieved 43 .…”

Changes in Cerebrospinal Fluid Proteins across the Spectrum of Untreated and Treated Chronic HIV-1 Infection

“…Factors contributing to the development of NSE include reduced treatment adherence, drug resistance and component drugs in the ART regime with limited CNS penetration [103][104][105][107][108][109][110]. Fortunately, adjustments in ART, taking into account drug resistance, drug potency and CNS drug penetration, can CSF proteome in HIV infection, page 7 usually halt disease progression and, to variable extent, reverse neurological deficits in many of these individuals [95,96], although for some NSE patients the course can be more complicated with recrudescence [103,105,111].…”