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Clin Infect Dis. 2018 Nov 20. doi: 10.1093/cid/ciy989. [Epub ahead of print]

Persistent low level viremia predicts subsequent virologic failure. Is it time to change the 3rd 90?

Author information

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States.
Makerere University- Walter Reed Project, Kampala, Uganda.
HJF Medical Research International, Kericho, Kenya.
HJF Medical Research International, Kisumu, Kenya.
Mbeya Medical Research Centre, Mbeya, Tanzania.
U.S. Army Medical Research Directorate - Africa/Nigeria, Abuja, Nigeria.
Department of Pediatrics, Uniformed Services University, Bethesda, Maryland, United States.



World Health Organization (WHO) guidelines identify HIV viral load less than 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 failure among participants with pLLV.


The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every six months. We evaluated participants prescribed ART for at least six months without virologic failure for pLLV. We used multinomial logistic regression clustered on participant to evaluate associations between pre-specified factors of interest and three 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, adjusting for key confounders.


We included 1,511 participants with 4,382 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 (HR: pLLV 200-499: 11.81, 95% CI: 1.08,3.02); pLLV 500-999: 22.36, 95% CI: 1.5252, 3.67).


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.


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