18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

LONGITUDINAL DYNAMICS OF PERSISTENT VIREMIA IN ELITE CONTROLLER PATIENTS VERSUS PATIENTS ON SUPPRESSIVE THERAPY

Antivir Ther 2009; 14 Suppl 1:A6 (abstract no. 4)

S Palmer^1,2, M King³, A Wiegand², T Miura⁴, B Block⁴, F Pereyra⁴, F Maldarelli², V Dahl¹, J Mellors⁵, B Walker⁴ and JM Coffin^6
1Swedish Institute for Infectious Disease Control, Karolinska Institute, Sweden; ²HIV Drug Resistance Program, NCI, NIH, Frederick, MD, USA; ³Abbott Laboratories, Abbott Park, IL, USA; ⁴Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, USA; ⁵University of Pittsburgh, Pittsburgh, PA, USA; ⁶Tufts University, Boston, MA, USA

BACKGROUND: Elite controllers are a rare subset of HIV type-1 (HIV-1)-infected individuals who maintain their viral RNA at undetectable levels (<50 copies/ml) without treatment. Patients on suppressive antiretroviral therapy also have undetectable viral RNA levels. In the present study, we compared the longitudinal dynamics of HIV-1 RNA levels in elite controllers versus patients on suppressive therapy.

METHODS: The viral RNA levels of 84 elite controllers were compared with samples from 163 patients suppressed on therapy to <50 copies/ml for 4–333 weeks. Viral RNA was measured using a real-time RT-PCR assay with single- copy sensitivity.

RESULTS: Viremia was detected in 85% of the samples from elite controllers (ranging 1–614 copies/ml) and from patients on suppressive therapy (ranging 1–43 copies/ml). Cross-sectional comparison of plasma HIV-1 RNA values revealed similar mean values of 0.5 log₁₀ copies (3 copies) for both groups of patients (P=0.95 based on Welch’s ANOVA). However, substantially greater between-patient variability in persistent viremia was observed among elite controllers compared with patients on suppressive therapy (P<0.0001 Levene’s test for homogeneity). A total of 441 longitudinal data points were available from 117 patients on suppressive protease inhibitor-based therapy and 24 elite controller patients. Consistent with the greater between-patient variability observed in the cross-sectional values, a wider range of HIV-1 RNA values for elite controllers was observed over time. In addition, based on a mixed-effects linear regression analysis, the within-patient variability was also substantially higher for elite controllers (SD of 0.60 log₁₀ copies/ml) compared with patients on suppressive therapy (SD of 0.38 log₁₀ copies/ml; ratio of variances 2.49; P<0.0001).

CONCLUSIONS: The majority of patients classified as elite controllers had detectable low-level viremia. While the overall mean level of viremia was similar to that of patients on suppressive therapy, longitudinal analysis revealed larger intra- and interpatient variability for elite controllers compared with patients on suppressive therapy. These substantial viral RNA fluctuations implicate a different source for the low-level viremia in the two groups, despite the similarity in levels. These findings suggest that elite controllers experience ongoing rounds of viral replication followed by immune response and viremic control.

2009-06-09
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