Abstract
We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50-1,000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, <50-3900) copies/mL after 14 (17.9, 0-58) months of LLV. Few patients maintained LLV for the entire 9 year period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p=0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.
Highlights
Combination antiretroviral therapy (ART) has lead to dramatic reductions in HIV-associated morbidity and mortality [1,2,3]
We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months
Combinations of protease inhibitor (PI) were used in only 9%, e.g., LPV/r with APV (5%), this combination was used as exclusive therapy in the only individual not receiving Nucleotide reverse transcriptase inhibitor (NRTI) therapy
Summary
Combination antiretroviral therapy (ART) has lead to dramatic reductions in HIV-associated morbidity and mortality [1,2,3]. Treatment goals for patients receiving ART include sustained undetectable viremia, [4,5,6] which is associated with favorable long-term clinical and immunological outcomes [7,8]. Undetectable viral load (VL) is generally defined as HIV RNA
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