U=U is supported by a single undetectable viral load in the context of good adherence

Simon Collins, HIV i-Base

The widespread adoption of U=U (undetectable=untransmittable) as a foundation for public health campaigns to eliminate HIV transmission is successfully challenging decades of HIV-related stigma.

While many UK doctors use the first undetectable viral load as the time to recommend U=U, some guidelines still recommended waiting for a confirmatory viral load result. Waiting for a second undetectable result is especially complicated during restrictions during COVID-19 and also delays this aspect of normalising life.

Given that the risk of viral load rebound is low after first becoming undetectable but is also possible after the second confirmatory test, comparing rates in these two situations might provide an evidence base to relax the recommendation for the confirmatory test.

Researchers with the UK-CHIC observational cohort analysed patterns of viral rebound in 1574 gay men starting ART during 2015 and 2016 with CD4 counts >350 cells/mm³ and more than one viral load <50 copies/mL.

The first undetectable viral load was reported after a median 2.5 months (IQR: 1.1 to 4.3) after ART initiation, with a second viral load 2.8 months later (IQR: 0.9 to 4.5). Over 4,707 person‐months of follow-up, 69 men (4.3%) had subsequent rebound: rate = 1.47/100 person months (95%CI: 1.16 to 1.86).

This compared to 176/1552 men (11.3%) with viral rebound after two initial consecutive undetectable results: rate = 0.82/100 (95%CI: 0.71 to 0.95) over 21,420 months of follow-up.

Although the rebound rate was slightly higher in the initial group, rates of rebound were low in both groups.

The differences between the two groups were even closer when using a <200 copies/mL rather than <50 copies/mL viral load threshold (0.62 vs 0.64).

This study noted that this approach is also likely to overestimate risk of viral rebound in the context of U=U as it will include all cause viral rebound, including low adherence. This is an important consideration given that U=U is dependent on good adherence.

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Although the international U=U campaign is already based on a single undetectable viral load, this UK dataset provides evidence to support this recommendation. The context of good adherence remains essential.

The study noted that as this was in gay men, the results might not be generalisable to other groups.

However, some of the HTB medical advisors still recommend maintaining viral load <50 copies/mL for more than six months. This is to have a greater  confidence that viral load will also be undetectable in genital fluids, especially in cases when baseline viral load was high (>100,000 copies/mL).

This might be practical in high-income settings where viral load tests are relatively inexpensive and there is flexibility for more frequent monitoring. It will have different practical implications in countries where viral load is only annual.

References

1. Okhai H et al. P54 Understanding patterns of early viral rebound in the current ART era: the UK CHIC study. BHIVA 2020 virtual conference, 22-24 November 2020. Poster abstract P54.
   https://onlinelibrary.wiley.com/toc/14681293/2020/21/S4

Simon Collins was a co-author of this study.