In summary, long-term follow-up data from the MONARK trial show that LPV/r monotherapy was able to maintain sustained viral suppression in 38 of the 56 patients who had already achieved HIV RNA <50 copies/mL at week 48. These results confirm those from previous studies which indicated that boosted PI monotherapy has

the ability to induce and maintain viral suppression in most patients [16]. However, first-line LPV/r monotherapy appeared somewhat less active than standard triple I-BET-762 in vitro therapy, and some patients showed persistent low-level viraemia. Higher levels of adherence may be required for constant suppression with LPV/r monotherapy than with LPV/r-containing combination therapy. Persistence of low-level viraemia with LPV/r monotherapy may increase the risk of selection

www.selleckchem.com/products/Gefitinib.html of drug-resistant viruses, whereas combination therapy with LPV/r is considered to rarely select for PI resistance in antiretroviral-naïve patients [17,18]. Long-term follow-up data from the MONARK study indicate that major PI-associated resistance mutations emerged in five of 83 patients after 40–90 weeks on treatment. Of note, however, three of five patients who were found to harbour selected major PI resistance mutations remained on LPV/r and underwent treatment intensification with NRTIs and achieved resuppression to HIV RNA <50 copies/mL, suggesting that control of viral replication could still be achieved with a PI/r-containing regimen. An important concern regarding LPV/r monotherapy is the possible lack of efficacy

in reservoirs, particularly the central nervous system (CNS) and male genital tract. LPV/r is highly protein bound to plasma proteins in blood. Poor penetration SPTLC1 of LPV/r through the blood–brain and blood–testis barriers has therefore been expected. Recently, a preliminary analysis reported an unexpected high failure rate on LPV/r monotherapy, which may be related to residual replication in the CNS compartment [19]. However, other data suggest significant activity for LPV/r monotherapy, at therapeutic concentrations, in the CNS [20]. In the context of a triple-drug regimen, low concentrations of LPV/r were found to inhibit HIV replication in this compartment, as the concentrations reached in the cerebrospinal fluid exceeded the 50% inhibitory concentration (IC50) for wild-type virus [21,22]. Of note, no neurological event was reported throughout the 96-week follow-up period in patients randomized to first-line LPV/r monotherapy in the MONARK trial. Furthermore, in a substudy of MONARK analysing the impact of 1 year of LPV/r monotherapy in the male genital tract, no local viral production was evident in the semen, despite undetectable local drug concentrations [23]. Limitations of this analysis include its open-label design. An additional limitation is the noncomparative analysis at week 96 because of the higher rate of premature terminations in the triple combination arm.