Starting HIV therapy with a viral load above 100,000 is associated with a lower chance of achieving an undetectable viral load

Michael Carter
Published: 28 November 2012

Starting HIV treatment with a viral load above 100,000 copies/ml is associated with a reduced chance of achieving an undetectable viral load within 48 weeks regardless of the combination of drugs used, according to the results of a meta-analysis published in HIV Medicine.

Overall, 82% of people with a baseline viral load below 100,000 copies had an undetectable viral load at week 48, compared to 73% who initiated therapy when their viral load was above this level. Having a detectable viral load for such a long time after starting treatment could be associated with a chance of developing drug-resistant virus.

“This meta-analysis of clinical trials shows a consistent association between higher baseline HIV-1 RNA [viral load] levels and a higher risk of treatment failure,” write the authors. “This analysis underscores the need for robust and simple treatment strategies for patients with high baseline HIV-RNA levels.”

The goal of antiretroviral therapy is an undetectable viral load. Ongoing HIV replication during treatment is associated with an increased risk of resistance, limiting the efficacy of therapy and future treatment options.

A number of factors have been associated with failure to achieve viral suppression. Outcomes in cohort studies suggest that one factor is baseline viral load, with people who have a viral load above 100,000 copies/ml being less likely to achieve suppression than those with lower viral loads.

However, the results from randomised controlled trials are conflicting. This is possibly because some were not large enough to detect differences in outcome according to baseline viral load.

To overcome this limitation, an international team of investigators conducted a meta-analysis of randomised controlled trials reporting on rates of viral suppression 48 weeks after starting HIV treatment according to baseline viral load.

Studies involving treatment-naive adult participants conducted between 2000 and 2012 were eligible for inclusion in the study.

A total of 21 studies involving 12,370 participants were included in the analysis. Median baseline CD4 cell counts varied between 161 and 390 cells/mm3, and median viral load at the time therapy was started ranged between 40,000 and 126,000 copies/ml.

Overall, 55% of participants had a viral load below 100,000 copies/ml when they started HIV treatment; 45% had a baseline viral load above that level.

Eight of the studies compared outcomes between people taking different NNRTIs; eight studies involved people taking different boosted protease inhibitors; the remaining five trials compared the efficacy of different drug classes, including newer treatment options such as integrase inhibitors and CCR5 inhibitors.

Therapy with abacavir (Ziagen, also in Kivexa) has been associated in some research with lower chances of viral suppression in people with a high viral load, compared to treatment based on tenofovir (Viread, also in Truvada, Atripla and Eviplera). In seven of the studies, Truvada was the only NRTI backbone prescribed.

Outcomes at week 48 showed that 82% of participants with a baseline viral load below 100,000 copies/ml had a viral load below 50 copies/ml, compared to 73% of those who started treatment when their viral load was above 100,000 copies/ml.

After taking into account possible confounding factors, the investigators found that the absolute difference in treatment efficacy between low and high viral load was 7%.

Differences in outcomes were regardless of the class of antiretroviral drugs used, and were 7% in NNRTI studies; 8% in studies comparing boosted protease inhibitors; and 6% in the trials comparing different treatment classes.

The difference in chances of viral suppression (8%) at week 48 was maintained when the investigators restricted their analysis to the studies which used Truvada as their only backbone. This showed that the use of abacavir was not driving the overall study findings.

The authors believe their findings have implications for HIV treatment strategies for individuals with a high viral load at the time they initiate antiretroviral therapy. “One option would be to start treatment with a boosted PI, which are associated with the lowest rates of treatment-emergent drug resistance,” they suggest. “Patients could then be switched to simplified treatments, such as fixed-dose combinations of NRTIs and NNRTIs, when the HIV-1 RNA was fully suppressed and the risk of treatment-emergent drug resistance lower.”

Reference

Stephan C et al. Impact of baseline HIV-1 RNA levels on highly active antiretroviral therapy outcome: a meta-analysis of 12,370 patients in 21 clinical trials. HIV Med, online edition. DOI: 10.111/hiv.12004, 2012.