Persistent low-level viral load is associated with failure, but risk is small

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Low but detectable viral load, in the range between three and 50 copies/ml, is associated with some risk of subsequent virological failure, but a viral load below three copies/ml with almost none, a study presented at the Tenth International Congress on Drug Therapy in HIV Infection (HIV10) in Glasgow has found.

The study also found that more patients on non-nucleoside (NNRTI)-based regimens had viral loads undetectable even to an ultrasensitive assay (under three copies/ml) than patients taking protease inhibitors (PIs). It is not clear why.

After eight months, 3.1% of the 28% of patients who had entered the study with a viral load between three and 50 copies/ml had a viral load over 50 copies/ml.

Glossary

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

assay

A test used to measure something.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

In contrast, none of the remainder, who had a baseline viral load below three copies/ml, had a viral load over 50 copies/ml.

The investigators found that the most reliable clinical cutoff  – the viral load threshold most strongly associated with eventual failure – was 20 copies/ml, but even so, only a quarter of people with viral loads over this figure eventually developed viral loads consistently above 50 copies/ml.

The study was conducted among a long-established prospective cohort of patients at the clinic of the Hospital Riuniti in Bergamo, Italy. All patients with a viral load under 50 copies/ml were enrolled and an enhanced viral load test was performed every four months, which can detect viral loads down to three copies/ml.

There were 900 patients in the cohort, 23% of them women. Reflecting the HIV epidemic in Italy, nearly half the cohort had acquired HIV heterosexually and 37% through injecting drugs. Their average age was 45. This was a treatment-experienced group, with an average time of 8.5 years on antiretroviral therapy. Three-quarters had taken four or fewer different ARV regimens but some had taken over ten different combinations. Treatment had been successful immunologically; the average CD4 count was 667 cells/mm3.

The study found that viral load changed little over the eight months of the study and that there was no evidence of further progressive viral suppression in these chronically infected patients: essentially HIV and antiretroviral treatment had reached an equilibrium state.

Nearly three-quarters (72%) of patients had a viral load under three copies/ml at baseline; four and eight months into the study, the proportion was 70% and 73% respectively. The remainder (28%) of the cohort had a viral load between three and 50 copies/ml at baseline, 26% at four months, and 23% at eight months.

Four per cent of the cohort had a viral load over 50 copies/ml at four months and 3.7% at eight months. All of them were patients with a viral load over three copies/ml as baseline.

They were not, in the main, the same patients at both time points: 38 patients had a single viral load ‘blip’ over 50 copies/ml, and only eight patients (0.9% of the whole group, 3.1% of those with a baseline viral load over three copies/ml) had over 50 copies/ml at months four and eight. Six of these eight patients had resistance tests but only one patient turned out to have developed a new (NNRTI-related) drug resistance mutation.

The only variable associated with viral load was the class of drugs taken. The proportion of patients with a viral load under three copies/ml at all three time points was 64% in patients taking NNRTIs, but only 52% in patients on PIs. Conversely, the proportion of patients with a viral load over 50 copies/ml at months four and/or eight was 2.5% in patients on NNRTIs and 8.5% in patients on PIs. This may reflect treatment history or longer treatment duration.

The study’s take-home message is that a low but detectable viral load does have clinical relevance but that it does not necessarily predict subsequent failure. Presenter Franco Maggiolo concluded that adopting ultrasensitive viral load assays in the clinic might not add a lot of clinically relevant information.

Reference

Maggiolo F et al. Low-level residual viraemia and risk of virological failure. Tenth International Congress on Drug Therapy in HIV Infection in Glasgow, abstract O115, 2010.