Background:  ART-experienced patients with drug resistance can have HIV-1 RNA suppressed to <50 copies using newer combinations of antiretrovirals, but low-level viremia often persists. Determining whether this persistent viremia is due to ongoing cycles of HIV-1 replication is important because partially suppressive regimens facilitate the emergence of drug resistance. To investigate the contribution of ongoing replication to persistent viremia in treatment-experienced patients, we conducted a study of short term drug intensification with the integrase inhibitor, raltegravir.

Methods:  We enrolled participants with a prior history of virologic failure and genotypic resistance who were subsequently suppressed to <75 copies/mL on a new regimen that did not contain raltegravir. Participants had baseline viral RNA levels determined during a 21-day period prior to drug intensification, then weekly during a 30-day intensification period with raltegravir 400 mg twice daily. Additional sampling was performed during the 6 weeks following intensification.

Results:  Eight participants had undergone an average of 4 suboptimal regimens prior to successful therapy, and were suppressed on combinations with an average GSS score of 2.1 (range 1.5 to 3) for a mean of 6.1 years prior to enrollment; 6 have completed intensification thus far. Median viremia prior to raltegravir was 0.31 log₁₀ HIV-1 copies/mL. No significant change in viral RNA levels was detected during intensification (median viral RNA 0.12 log₁₀ copies/mL, P = 0.88) or following intensification (median 0.08 log₁₀ copies/mL, P =0.41). Mean CD4 cell numbers were not significantly different after 30 days of intensification. Raltegravir was well tolerated with no adverse effects.

Conclusions:  Raltegravir intensification of treatment-experienced patients on a suppressive regimen did not lower the level of persistent viremia. Low level viremia in treatment-experienced patients is not the product of ongoing cycles of HIV-1 replication in short-lived cells, even in patients with a prior history of drug resistance.