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Intensification of Already Suppressive Therapy with Raltegravir Had No Impact on Low-Level (sub-50-copy) Viremia
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Mark Mascolini
XVIII International Drug Resistance Workshop, June 9-13, 2009, Fort Myers, Florida
Intensifying already suppressive therapy with raltegravir, efavirenz, lopinavir, or atazanavir had no impact on low-level (sub-50-copy) viremia in any of 18 people who beefed up their regimen for 4 or 8 weeks [1]. Frank Maldarelli (National Cancer Institute, Frederick, Maryland) and colleagues believe the findings disprove the hypothesis that persistent low-level viremia results from ongoing complete cycles of viral replication. If it did, intensification would be expected to push already low viral levels even lower.
Clinicians at three centers intensified treatment in 18 people taking a protease inhibitor (PI) or nonnucleoside regimen that kept their viral load below 50 copies for more than 6 months. For 4 weeks, 9 people added the integrase inhibitor raltegravir, 2 added the nonnucleoside efavirenz, and 2 added the PIs lopinavir/ritonavir. For 8 weeks, 5 people added the PI atazanavir to their regimen. Before, during, and after intensification, the investigators measured low-level viremia 257 times with an assay that can spot a solitary HIV RNA copy in plasma.
The 16 men and 2 women enrolled had kept their viral load below 50 copies for 0.7 to 15 years. Median CD4 count at intensification stood at 536. Before intensification, the high-sensitivity assay spotted median loads of 1.7 to 2.7 copies in the four treatment groups. During intensification, those levels ranged from 1.6 to 5.6 copies. After intensification, low-level viremia ranged from 1.1 to 4.8 copies. None of the differences from one period to the next was statistically significant. Nor did low-level viremia change significantly in any individual.
Plasma concentrations of study drugs reached therapeutic levels in all study participants. Resistant virus did not explain failure to reduce already low HIV RNA levels with intensification. CD4 counts remained stable during and after the study. Everyone tolerated intensification well, with no serious side effects.
HIV experts have advanced two theories to explain persistent residual HIV RNA in plasma of people with loads under 50 copies: viral production from long-lived chronically infected cells, or ongoing complete cycles of viral replication. Failure to cut already low RNA levels with intensification favors the first explanation.
Partial results of this study appeared online just before the Resistance Workshop [2].
References
1. Dinoso J, Jones J, McMahon D, et al. Antiretroviral intensification does not reduce persistent HIV-1 viremia on therapy. XVIII International Drug Resistance Workshop. June 9-13, 2009. Fort Myers, Florida. Abstract 10.
2. Dinoso JB, Kim SY, Wiegand AM, et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci USA. 2009;106:9403-9408.
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