Increased risk of ART failure after low-level viraemia in a large South African cohort

Polly Clayden, HIV i-Base

Viral load cut-off as defined by WHO guidelines fails to identify a significant number of HIV positive people at risk for virological failure, according to findings from South Africa presented at the 11th INTEREST workshop.

Current WHO ART recommendations define failure as viraemia above 1000 copies/mL during treatment. In high-income countries, with stricter viral load cut-off (50 copies/mL), detectable viral load below 1000 copies/mL during ART (low-level viraemia) has been linked to treatment failure.

The currently recommended preferred first-line ART regimen has a low genetic barrier to resistance: NNRTI + 2NRTI.

Lucas Hermans presented findings from an evaluation of low-level viraemia and its impact on ART failure in a large South African cohort managed according to WHO guidelines.

The study was conducted across 19 urban and 38 rural HIV treatment sites. Adult participants were included if they had received ART for 20 weeks or more and had viral load monitoring.

Low level viraemia was defined as 50-1000 copies/mL and stratified by level: 51-199, 200-399 and 400-999 copies/mL, and duration. Outcomes were ART failure above 1000 copies/mL and switch to second-line. The investigators used Cox proportional hazard models corrected for sex, age and baseline CD4, to estimate the association between low-level viraemia and subsequent viral failure in the subset of participants with 52 weeks or more of first-line ART without failure.

Overall 71,056 participants met inclusion criteria: 67,380 treated with first-line ART; 1,602 second-line ART and 2,074 with both. Virological failure on ART occurred in 21.6% of people on first-line ART; 35% of these resuppressed <1000 copies/mL on the same regimen.

Low level viraemia occurred in 12% per year; 23.1% of participants had low-level viraemia at any time during follow up and this was persistent in 21.3% of cases.

Low-level viraemia between 51-199 copies/mL was common (59%). It was associated with increased hazard of failure of first-line ART, HR 3.0 (95% CI 2.8 to 3.3); ART failure without resuppression on same regimen, HR 3.2 (95% CI 3.0 to 3.5); and switching to second line, HR 2.9 (95% CI 2.4 to 3.4), compared to <50 copies/mL. The investigators saw a further increase in risk of failure with higher ranges and duration of low-level viraemia. And lower baseline CD4 was independently associated with low-level viraemia.

Dr Hermans noted that despite these risks, WHO guidelines do not recommend clinical intervention in cases of repeated low-level viraemia below the cut-off of 1000 copies/mL. “This poses concerns for long term virological suppression in WHO-guided treatment programmes”, he suggested.


Hermans LE et al. Increased risk of treatment failure after low-level viraemia in a large cohort of South African HIV positive patients treated according to under WHO guidelines. 11th INTEREST, 16-19 May 2017, Lilongwe, Malawi. Oral abstract 7.

A similar earlier analysis from this study was presented at CROI 2017:

Hermans LE et al. Increased risk of cART failure after low-level viremia under WHO guidelines. CROI 2017. 13-16 February 2017. Seattle, Washington. Oral abstract 113. (abstract) (webcast)

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