Protease inhibitor monotherapy is not associated with increased viral replication in lymph nodes.
ABSTRACT There are concerns about residual viremia in sanctuary sites among patients on protease inhibitor monotherapy, so we aimed to study viro-immunological parameters in tonsil's lymphoid tissue of patients on HAART and on protease inhibitor monotherapy. Despite fully suppressed serum HIV viral load, we found viral replication in both groups; in addition, more patients had detectable proviral DNA among those on HAART, compared to those on protease inhibitor monotherapy (P = 0.08), supporting the absence of a deleterious effect of protease inhibitor monotherapy.
Article: Protease inhibitor monotherapy.[Show abstract] [Hide abstract]
ABSTRACT: The present review focuses on recent data about boosted protease inhibitor monotherapy for maintenance of HIV virological suppression. Until recently most of the trials of boosted protease inhibitor monotherapy have studied lopinavir/ritonavir monotherapy. These trials showed a slightly inferior efficacy of lopinavir/ritonavir monotherapy than that of lopinavir/ritonavir and two nucleosides. Two clinical trials [Monotherapy in Europe with TMC114 (MONET) and Monotherapy inhibitor protease (MONOI)] have shown that darunavir/ritonavir monotherapy has also a slightly lower efficacy for maintenance of virological suppression than darunavir/ritonavir with two nucleosides. The risk of resistance development is minimal and patients who fail this strategy can be re-suppressed again by adding nucleosides or switching to a triple therapy regimen without having lost therapeutic options. MONOI has also shown limb fat recovery in patients receiving darunavir/ritonavir monotherapy and good penetration of darunavir in the seminal fluid. There are still conflicting views about the ability of boosted protease inhibitor to protect the central nervous system from HIV replication. There are no randomized clinical trials showing a higher risk of discordant HIV replication in the cerebrospinal fluid in patients exposed to monotherapy. There are insufficient data of monotherapy with atazanavir/ritonavir. There currently is no consensus about the role of boosted protease inhibitor monotherapy for the treatment of HIV infection. It is clear that suppression can be maintained in a large proportion of patients without exposing patients to a substantial risk of resistance development, but the precise role of this strategy is still undefined.Current Opinion in Infectious Diseases 02/2011; 24(1):7-11. · 5.03 Impact Factor
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ABSTRACT: HIV-1 protease inhibitors (PIs) are among the most effective antiretroviral drugs. They are characterized by highly cooperative dose-response curves that are not explained by current pharmacodynamic theory. An unresolved problem affecting the clinical use of PIs is that patients who fail PI-containing regimens often have virus that lacks protease mutations, in apparent violation of fundamental evolutionary theory. Here, we show that these unresolved issues can be explained through analysis of the effects of PIs on distinct steps in the viral life cycle. We found that PIs do not affect virion release from infected cells but block entry, reverse transcription, and post-reverse transcription steps. The overall dose-response curves could be reconstructed by combining the curves for each step using the Bliss independence principle, showing that independent inhibition of multiple distinct steps in the life cycle generates the highly cooperative dose-response curves that make these drugs uniquely effective. Approximately half of the inhibitory potential of PIs is manifest at the entry step, likely reflecting interactions between the uncleaved Gag and the cytoplasmic tail (CT) of the Env protein. Sequence changes in the CT alone, which are ignored in current clinical tests for PI resistance, conferred PI resistance, providing an explanation for PI failure without resistance.The Journal of clinical investigation 08/2013; · 15.39 Impact Factor
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ABSTRACT: We report the evolution of chronic infection with human immunodeficiency virus type 1 (HIV-1) in a patient treated with stavudine plus didanosine, whose CD4+ lymphocyte count progressively decreased, despite a sustained plasma viral load <20 copies/mL. After 12 months of therapy, treatment was switched to zidovudine plus lamivudine plus nelfinavir. CD4+ T cell count decreased from 559 x 10(6)/L at month 0 to 259 x 10(6)/L at month 12. Plasma viral load decreased from 21,665 HIV-1 RNA copies/mL at baseline (month 0) to <20 copies/mL after 1 month of therapy with stavudine plus didanosine, and remained below 20 copies/mL until month 12, but always >5 copies/mL. Viral load in tonsilar tissue at month 12 was 125,000 copies/mg of tissue. After the change to triple-drug therapy, the plasma viral load decreased to 5 copies/mL, the CD4+ T cell count increased to 705 x 10(6)/L, and the viral load in tonsilar tissue decreased to <40 copies/mg of tissue at month 24. A low level of HIV-1 replication could explain the lack of immunologic response in patients with apparent virological response.Clinical Infectious Diseases 02/2000; 30(2):392-4. · 9.42 Impact Factor