Persistent low-level viraemia – a serious threat to treatment programmes in low-resourced countries
Low-level viraemia is linked to treatment failure, but we are failing to make best use of effective HIV treatment as a result of inadequate viral load monitoring.
Persistent low-level viraemia – where low levels of viral replication continues in the presence of antiretroviral treatment (ART) – is common in South Africa and a strong predictor of subsequent treatment failure.
The study, published in last month’s Lancet Infectious Diseases, is the first ever from a low- or middle-income country to examine whether consistently low, but detectable levels of HIV in the body will ultimately cause treatment to fail.
It offers unsurprising, but substantial empirical evidence demonstrating that a persistent inability to monitor treatment effectiveness can be problematic in low-resourced settings.
71,000 adults living with HIV from rural and urban areas of South Africa were included in the study. Patients were treated with first- or second-line ART regimens, and monitored according to WHO guidance between 2007 and 2016. Currently, the WHO threshold for virological failure (i.e. treatment failure) is set at over 1,000 copies/ml.
The study found that around a quarter (23%) of patients on first-line ART had low-level viraemia during two years of follow-up, and that this was a strong predictor of subsequent treatment failure, leading patients to switch to second-line ART.
Rates of treatment failure with low-level viraemia were also higher when compared to comparable studies from high-income countries.
Moreover, people who had viral loads of 51 to 199 copies/ml had double the risk of treatment failure compared to those with viral loads of less than 50 copies/ml, and this applied to people on both first- and second-line ART.
For patients with a viral load in the range of 400 to 999 copies per ml, the risk of treatment failure was nearly five times higher for those on first-line ART, and nearly seven times higher for those on second-line ART, compared to those with viral loads of under 50 copies/ml.
About 60% of the reported instances of virological failure on first-line ART and about 73% of those observed on second-line ART were recorded in the first viral load monitoring test. This suggests that non-adherence or pre-treatment drug resistance might be affecting treatment outcomes.
Indeed, this research comes in the wake of growing evidence that HIV drug resistance, particularly to non-nucleotide reverse transcriptase inhibitor (NNRTI) drugs which make up the backbone of WHO-recommended treatment options, is increasing rapidly across the region.
Reducing exposure to detectable viraemia is therefore critical for improved clinical outcomes, but also to ensure resistant virus is not replicating, resulting in a loss of treatment options – of which there are few second-line options already.
Overall, the study indicates that low-level viraemia is a serious threat to treatment programmes in low-income and middle-income countries. Yet a lack of access to viral load testing and adequate options for second-line treatment cripple effective management of persistent low-level viraemia.
The authors call on WHO guidance to change and recognise low-level viraemia as an early warning indicator for treatment failure. Particularly as the threshold for treatment failure in high-income countries is set at 200 ml/copy.
In an accompanying comment in the Lancet, Antonella Castagna said: “Results from this study should prompt us to reconsider the definition of virological failure, the frequency of viral load monitoring, and the timing of switching to second-line regimens, to reduce the exposure to detectable viraemia, the risk of clinical progression and development of HIV drug resistance and, ultimately, the loss of therapeutic options.”