The MONOI study, sponsored by the French national AIDS research agency, included 242 participants who also were on combination antiretroviral therapy with viral load below 400 copies/ml for at least six months and below 50 copies/ml at study entry.
Patients in this study were first treated for eight weeks with a standard three-drug regimen containing darunavir/ritonavir plus two NRTIs, but the dose was 600/100 mg twice-daily rather than 800/100 once-daily. After this induction period, participants were randomly assigned to either remain on the combination regimen or drop the NRTIs and continue on darunavir/ritonavir monotherapy. Both the patients and their doctors knew which drugs they were taking.
A total of 225 participants went forward to the randomisation phase of the study. Three-quarters were men, the median age was 46 years and the median CD4 cell count was about 600 cells/mm3. Participants had never experienced treatment failure while using a protease inhibitor and had not previously used darunavir. The average duration of antiretroviral treatment experience was about eight years.
Treatment failure was defined as two consecutive viral load measurements above 400 copies/ml or changing or discontinuing study treatment. Again, the study was statistically powered to be able to show whether darunavir/ritonavir monotherapy was non-inferior to combination therapy.
In an intent-to-treat analysis, 87% of patients taking darunavir/ritonavir monotherapy maintained a viral load below 400 copies/ml through 48 weeks, compared with 92% of those taking standard triple therapy, demonstrating that monotherapy was non-inferior. In a per protocol analysis, 94% of patients taking monotherapy and 99% taking triple combination therapy maintained a viral load below 400 copies/ml, once again demonstrating non-inferiority.
Three patients taking monotherapy experienced virological failure, compared with none of those taking combination therapy. One had a low blood level of darunavir/ritonavir, suggesting inadequate adherence. However, no mutations associated with resistance to darunavir/ritonavir were seen in patients experiencing viral rebound and re-starting NRTIs led to re-suppression of viral load.
Similar proportions of patients changed their treatment during follow-up, and three people in both arms stopped study therapy. Similar numbers of serious adverse events were reported in the monotherapy and combination therapy arms (14 and 15, respectively).
One case of HIV encephalitis and one case of neurological symptoms were observed in the monotherapy arm, which a safety committee classified as possibly related to the treatment regimen under study.
The investigators concluded that darunavir/ritonavir monotherapy is a "viable alternative to standard triple therapy" that is less expensive and avoids NRTI toxicities with "no significant downstream consequences."
"The vast majority did not have even a single blip," MONOI principle investigator Christine Katlama told reporters at a press conference. While a proportion of patients need NRTIs to maintain undetectable viral load, these individuals can easily re-suppress HIV by restarting NRTIs and no resistance developed. However, she added, the effects of less than perfect adherence are more apparent when patients use a single drug.
Asked about the danger of non-AIDS-related events associated with ongoing HIV replication, Katlama suggested that these problems were typically seen in people with a few thousand, not a few hundred, copies/ml. MONET principle investigator Jose Arribas added that occasional viral load blips may not carry the same risk as continuous low-level viral replication.