Viral load level when suppressed <1000 predicts future rebound: 3-monthly monitoring required
Simon Collins, HIV i-Base
Several studies at IAS 2023 in different populations and settings reported on the risk of viral failure when HIV viral load is suppressed to less than 1000 but not to less than 50 copies/mL.
This has implications for both clinical care and the new WHO guidelines on treatment as prevention.
Although similar results were reported more than 20 years ago in the early ART era, it is important to show that this principle of drug resistance is just as relevant with modern HIV combinations.
The first study is a poster from the Gaitonde Center for AIDS Research and Education, Infectious Diseases, Chennai, India.
This was a longitudinal retrospective analysis of viral load results from 3498 people living with HIV and treated at this centre between 2013-2018. Of these, 2965 (84.8%) were fully suppressed (<40 copies/mL) and 533 (15.2%) had low level viraemia (LLV) but less than 1000 copies/mL.
During follow-up, 126/2965 people with full suppression had viral load rebound to >1000 copies/mL. This was 3.6% of the overall cohort and 4.3% of people who were fully suppressed. By comparison, 217/533 people with LLV rebounded to >1000 copies/mL. This was significantly higher, accounting for 6.2% of the overall cohort and 31% of those with LLV.
There was a clear link between the higher bands of low-level viraemia and a higher subsequent risk of treatment failure. See Table 1.
People on first-line ART had a higher incidence of VF (HR 15.8, 95% CI: 11.4 to 21.9) than second-line (HR 5.6, 95% CI: 4.1 to 7.7), perhaps because of the urgency of better adherence.
Table 1: Risk of viral rebound >1000 c/mL by viral load and treatment line
|Risk of rebound >1000 copies/mL|
|LLV-I: 40 to 199||225||12.9 (7.9 to 21.1)||4.1 (2.8 to 6.1)|
|LLV-II: 200 to 399||130||13.3 (8.3 to 21.4)||6.2 (4.0 to 9.6)|
|LLV-III: 400 to 999||178||22.8 (15.2 to 34.3)||8.1 (5.5 to 12.0)|
Other similar studies reported similar outcomes in different populations.
This included a retrospective analysis of 670 children and adolescents living with HIV in Tanzania, which reported the same association between levels of LLV and future risk of viral failure. 
Another poster reported a retrospective analysis of 8610 adults in Zambia with a viral load result >1000 copies/mL between April 2018 and January 2022. This study reported that people who had a previous low-level viral load result (60 to 1000 c/mL) were 3.4-fold more likely to have viral failure compared to those with a previous undetectable viral load <60 copies/mL. 
These posters are important to report because of the new WHO policy brief that defines three key categories for HIV viral load results: unsuppressed (>1000 copies/mL), suppressed (detected but ≤1000 copies/mL) and undetectable (viral load not detected by test used). [4. 5]
Undetectable includes results from both PCR tests sensitive to 20, 40 or 50 copies/mL and dried blot spot (DBS) tests where the cut-off is slightly higher at 300 or 400 copies/mL.
It also states that having suppressed viral load between 200 to <1000 copies/mL means having such a negligible risk for sexual transmission without a condom that the risk of transmission is close to zero.
This policy brief was based on a review published in the Lancet and released at the same time. 
This important document resolves the grey area between having an undetectable viral load <50 copies/mL using PCR tests, and settings where the threshold of 1000 copies/mL is used to manage care.
Having a zero risk of sexual transmission is based on results from the PARTNER and other studies but WHO guidelines use the threshold of 1000 copies/mL to define viral failure in low- and middle-income countries (LMICs).
The new WHO policy now enables people globally to benefit from lifting the fear associated with a risk of transmitting HIV. This is significant for connecting people to the global U=U campaign. 
However, it is essential to also remember that for most people, viral load suppression to between 200 and 1000 is not a stable state but a temporary situation.
It requires more frequent viral load monitoring – every three months – with more careful adherence, to determine whether viral load will either become undetectable or continue to rebound to >1000 copies/mL.
Thinking of ‘suppression’ as a stable state misses that viral load can rebound in some cases within a few months to levels that could enable sexual transmission.
- Dinesha TR et al. HIV-1 Low level viremia predicts virological failure in first-line and second-line ART experienced individuals in India. IAS 2023, poster abstract EPB0115.
- McKenzie KP et al. Low-level viremia as a risk factor for virologic failure in children and adolescents living with HIV. IAS 2023, poster abstract EPB0117.
- Mwamba D et al. Can HIV low level viremia predict future anti-retroviral treatment failure? A retrospective cohort analysis from Zambia. IAS 2023, poster abstract EPB0120.
- WHO policy brief. The role of HIV viral suppression in improving the individual health and reducing transmission. 22 July 2023.
- Clayden P. WHO endorses “zero” transmission risk for people with HIV with an undetectable viral load. HTB, 26 July 2023.
- Broyles LN et al. The risk of sexual transmission of HIV in individuals with low-level HIV viraemia: a systematic review. Lancet 2023; 21 July 2023.
- U=U and Prevention Access Campaign.