Persistent Low-level Viremia Predicts Subsequent Virologic Failure: Is It Time to Change the Third 90?

Clin Infect Dis. 2019 Aug 16;69(5):805-812. doi: 10.1093/cid/ciy989.

Abstract

Background: World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic.

Methods: The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200-499, and 500-999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure.

Results: We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200-499 and 500-999 copies/mL each, with substantial variation by site. Protease inhibitor-containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200-499: HR, 1.81 [95% CI, 1.08-3.02]); pLLV 500-999: HR, 2.36 [95% CI, 1.52-3.67]).

Conclusions: Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL.

Keywords: ART; HIV; low-level viremia; virologic failure.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Africa / epidemiology
  • Anti-HIV Agents / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Treatment Failure
  • Viral Load*
  • Viremia / drug therapy*
  • Viremia / epidemiology
  • World Health Organization
  • Young Adult

Substances

  • Anti-HIV Agents