National HIV treatment programmes should not wait until people with HIV have viral loads above 1000 copies/ml to provide enhanced adherence counselling, Nigerian researchers report in the journal Lancet Global Health.
In a study of more than 100,000 people, the research group found that at least one in ten people with a detectable viral load below 1000 went on to experience a viral load above this level and 3% experienced treatment failure.
All were at risk of developing drug resistance and might need to switch to more expensive second-line treatment.
The study also found that small increases in viral load below 1000 – for example from 100 to 400 – resulted in big increases in the risk of virological non-suppression and treatment failure.
The researchers say that physicians and treatment programmes should be more alert to the risks of low-level viraemia and act quickly when it is detected, to avoid serious long-term consequences. Low-level viraemia is usually a consequence of missing multiple doses of antiretroviral medication, or non-adherence.
Low-level viraemia (between 50 and 200) raises the risk of virological failure and drug resistance. A large study of people with HIV in Europe showed that low-level viraemia on two consecutive viral load tests more than doubled the risk of virological failure within the following two years.
Nigerian national guidelines recommend that viral load testing should be carried out six and 12 months after starting treatment and every year thereafter.
They recommend that people who had a viral load above 1000 should receive enhanced adherence counselling and a repeat viral load test three months later. If viral load is not suppressed below 1000 on the second test, a treatment switch should be considered.
In 2021, the World Health Organization updated its guidance on viral load monitoring to recommend that people with viral load above 50 copies and below 1000 should receive enhanced adherence counselling and a repeat viral load test after three months.
The retrospective study looked at viral suppression at the first viral load test in 402,668 adults with HIV between 2016 and 2021 in 18 states in Nigeria. The country has approximately 1.7 million people living with HIV.
The researchers classified viral load test results as either virologically suppressed (below 50), non-suppressed (above 1000) or at one of three levels of low-level viraemia (51-199, 200-399 or 400-999).
They carried out two analyses. The first looked at the prevalence of low-level and non-suppressed viraemia in 402,668 adults with at least one viral load test result. The second analysis looked at the virological outcomes of 112,316 people who had more than two viral load test results and who were either virally suppressed or had low-level viraemia at their first viral load test.
The population included in the prevalence analysis was predominantly female (67%). Almost half (48%) had begun antiretroviral treatment between March 2019 and April 2021 during the Nigeria HIV Treatment Surge, a national effort to diagnose and treat more people with HIV that enrolled around 450,000 people onto treatment.
At the first viral load test during the follow-up period, 72% had a viral load suppressed below 50, 11% were non-suppressed and 16% had low-level viraemia (63% of these were in the 50-199 range).
Among the small subset of people on second-line treatment (n=5,986), 54% were virologically suppressed, 21% were non-suppressed and 24% had low-level viraemia (59% of these in the 50-199 range).
"Low-level viraemia proved to be a stronger risk factor for virological non-suppression and virological failure than any other potential risk factor."
Rates of viral suppression improved each year, increasing from 49% in 2016 to 81% in 2021. The rate of non-suppression fell from 26% in 2016 to 6% in 2021 and the rate of low-level viraemia from 24% in 2016 to 12% in 2021.
The virological outcomes analysis included 197,729 people with at least three viral load test results. Of these, 80% had a viral load below 50 at their first viral load test and 20% had low-level viraemia.
After adjusting for sex, age at ART initiation, ART duration and regimen, men were 7% more likely to experience virological non-suppression and virological failure.
Younger age was associated with increased risks of virological non-suppression and virological failure, with the greatest risk of both outcomes seen in 18 and 19-year-olds. Participants in this age group were 70% more likely to experience virological failure compared to people over 50 years.
Greater time on treatment modestly increased the risk of virological non-suppression and virological failure. Receiving treatment with an integrase inhibitor (dolutegravir in almost all cases) reduced the risk of virological non-suppression by 21% and the risk of virological failure by 60%.
Low-level viraemia proved to be a stronger risk factor for virological non-suppression and virological failure than any other potential risk factor.
In an adjusted analysis, people with low-level viraemia between 51-199 had a 48% higher risk of virological non-suppression and an 80% higher risk of virological failure compared to those who were virologically suppressed (p<0.0001).
Low-level viraemia between 200 and 399 raised the risk of virological non-suppression by 73% and more than doubled the risk of virological failure. People with low-level viraemia between 400 and 999 had twice the risk of virological non-suppression and three-and-a-half times the risk of virological failure compared to those who were virologically suppressed.
To put these risks in context, the investigators reported that one in ten people with low-level viraemia went on to have virological non-suppression (viral load above 1000) at their next viral load test. Almost 3% went on to experience virological failure.
"Drug resistance data could help clinicians optimise treatment for patients with low-level viraemia."
What happened to people after a virological non-suppression result? Of those with virological non-suppression, 11,399 had a subsequent viral load result. These tests showed that 69% re-suppressed viral load below 50, 11% had low-level viraemia and just under 20% went on to experience virological failure.
Virological re-suppression after a non-suppression result was slightly more likely in people taking dolutegravir-based treatment. Dolutegravir-based treatment also reduced the risk of subsequent virological failure.
“Current guidelines that use 1,000 copies/ml to initiate patient-level strategies to improve suppression, such as enhanced adherence counselling, miss an important opportunity to prevent virological non-suppression for patients with low-level viremia,” the study authors conclude. They say their study findings add to the evidence that viral load monitoring benchmarks need to be revised downwards from 1000 to 50.
In Nigeria’s national HIV programme, the response to the risks posed by low-level viraemia has been to increase the number of facility- and community-based workers who can provide enhanced adherence counselling. At the same time, intensive monitoring of virological outcomes in people with low-level viraemia enables the national HIV programme to identify where service improvements are needed. The study authors say that national HIV programmes should refine their use of viral load indicators.
Rather than using a cut-off of 1000 to track performance, programmes should consider using suppression below 50, low-level viraemia below 200 and viral load above 200 to monitor progress in HIV control. More refined measurement of viral load outcomes should be complemented by improved laboratory capacity so that drug resistance data can help clinicians optimise treatment for patients with low-level viraemia.
Chun HM et al. Low-level viremia among people living with HIV in Nigeria: a retrospective longitudinal cohort study. Lancet Global Health 10: e815-24, 2022.