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

Allahna Esber*, Christina Polyak, Francis Kiweewa, Jonah Maswai, John Owuoth, Lucas Maganga, Yakubu Adamu, Patrick W. Hickey, Julie A. Ake, Trevor A. Crowell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish
Article numberciy989
Pages (from-to)805-812
Number of pages8
JournalClinical Infectious Diseases
Issue number5
StatePublished - 16 Aug 2019
Externally publishedYes


  • ART
  • HIV
  • low-level viremia
  • virologic failure


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