Standard-of-care antiretroviral therapy is based on a combination of at least three antiretroviral drugs including two
nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus a third drug among these options:
- 1 nonnucleoside reverse transcriptase inhibitor
- 1 boostedprotease inhibitor (PI)
- 1 integrase inhibitor
However, NRTIs can cause negative side effects such as kidney or bone toxicity. It is thus advisable to investigate therapeutic strategies that avoid prolonged exposure to these drugs.
In this contest, monotherapy with boosted PIs is particularly attractive. Guidelines consider this approach in cases of NRTI-related toxicity or intolerance. In addition, PI monotherapy could improve adherence, decrease costs, and preserve future treatment options.
Nonetheless, there are still unsolved questions. One of the concerns with monotherapy is whether it can maintain control of viral replication in different compartments, particularly in cerebrospinal fluid. The cerebrospinal fluid (CSF) is a crystal clear fluid that bathes the brain and the spinal cord. It has three important vital functions:
- To Keep the brain floating, acting as a cushion or shock absorber inside the skull in case of a blow.
- To act as the vehicle to transport nutrients to the brain and eliminate waste.
- To flow between the skull and the spinal cord to compensate changes in the amount of blood in the brain, maintaining a constant pressure.
Some authors have associated viral replication in the CSF to a higher risk of neurocognitive impairment and have suggested that monotherapy with IPs may be inadequate in this compartment.
The objective of the MONOKAL study, conducted in collaboration with various HIV/AIDS specialists from diferent centers and leaded by José Ramón Santos, from de Fight AIDS Foundation, was to explore the long-term virological efficacy of lopinavir/ritonavir monotherapy in CSF and neurocognitive function.
The study was done in patients on lopinavir/ritonavir-based monotherapy (17 people) and standard triple therapy (another 17 people) for at least 96 weeks and who maintained suppression in their viral load.
Results obtained, that have been published recently in the PlosOne scientific journal, indicate that lopinavir/ritonavir monotherapy seems to be safe for CNS functioning: suppression of HIV in CSF and neurocognitive status are similar in both groups of patients.