- Persistent viral loads between 50 and 199 copies /mL are associated with deleterious consequences.
- In the future, a consistent definition of VF and low-level viremia (LLV) is necessary for interpreting results and comparing studies.
Definition of virologic failure (VF) and virologic thresholds to switch combination antiretroviral therapy (ART), vary by region and differ based on the organizations making recommendations. One of the reasons for this variability is the conflicting data on the clinical and virologic consequences of LLV, (i.e. a detectable viral load (VL) that is
The NHS is a prospective, multicenter, open cohort comprised of HIV-positive Department of Defense beneficiaries. For this retrospective analysis, 2006 subjects (median age 29,2 years, 93% male, 41% African-American (AA)) were included: subjects who initiated ART after 1/1/1996 and had at least two documented VLs six months after ART initiation, and while on ART. Follow-up ended on October 30, 2017.
VF was defined as a confirmed VL ≥200 copies/mL, or any VL>1000 copies/mL. 383 subjects (19%) experienced VF Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (viral load of 50-199 copies/mL on
In the Cox regression models (adjusted for demographics, viral load, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to commencing ART), subjects with hLV and pLLV had a greater hazard for VF; AA ethnicity, antiretroviral drugs use prior to ART, and a higher viral load at ART initiation were associated with VF. iLLV, older age at ART initiation and use of a non-nucleoside reverse transcriptase inhibitor or an integrase strand transfer inhibitor-based regimen were protective. The subgroup analysis (n=934), initiating ART after 2007 (FDA approved the tenofovir/emtricitabine/efavirenz regimen in mid-2006), showed similar association with pLLV and VF.
The strengths of the study are the large sample size, the long follow-up interval and the collection of several data points on a regular basis. Of note, NHS subjects initiate ART relatively early in the course of the illness, and have unrestricted access to health care and medications and low drug use factors; analysis used time-updated variables and accounted for treatment interruptions.
Limitations: the cohort is predominantly male; adherence data has not been collected since the inception of the cohort; clinical consequences were not examined.