Severe obesity is a risk factor for virological failure

BRUSSELS — There was no significant difference between obese and nonobese patients with HIV in the time to undetectable viral loads after treatment initiation with an efavirenz-based regimen, researchers reported here at EACS 2013.

However, severe obesity warrants careful consideration by clinicians because individuals weighting more than 95 kg were more likely to experience a viral load rebound after achieving an initial virological suppression, suggesting that the standard efavirenz (Sustiva, Bristol-Myers Squibb) dosage may not be sufficient in obese individuals, they said.

"The response to [efavirenz] should be monitored carefully in patients with severe obesity," Catia Marzolini, PharmD, PhD, of the University Hospital Basel in Switzerland, said during a presentation.

Catia Marzolini

Marzolini and colleagues used data from a large European collaborative study, COHERE, to assess the incidence of virological failure in obese patients treated with regimens containing efavirenz compared with nonobese patients. The researchers used Cox regression analyses to determine the association between weight and time to first undetectable viral load (≤50 copies/mL) after treatment initiation, as well as the time to viral load rebound, defined as two consecutive viral load levels of >50 copies/mL after initial viral suppression during 5 years of follow-up. Obese patients were grouped according to their weight (group I, <80 kg; group II, ≥80 to <85 kg; group III, ≥85 to <90 kg; group IV, ≥90 to <95 kg; and group V, ≥95 kg).

The study included 13,431 patients, of whom 10,455 (77.8%) had normal-to-low weight (group I, reference group), with 1,178 (8.8%) in group II, 731 (5.4%) in group III, 463 (3.5%) in group IV and 604 (4.5%) in group V. Among the entire cohort, 11,310 (84.2%) achieved viral suppression, of whom 3,867 (34.2%) experienced a subsequent viral load rebound (P=.0003).

After adjusting their analyses for demographic, viral and treatment-related factors, as well as for cohort and calendar year, the researchers found that the time to undetectable viral load was not significantly different among weight groups. However, the time to subsequent rebound was significantly shorter in individuals weighting at least 95 kg (adjusted relative hazard [ARH]=1.28; 95% CI, 1.09-1.50) as compared with those weighting less than 80 kg.

Additional analyses indicated that the time to viral rebound was driven primarily by Caucasian race and male gender, "suggesting gender and ethnicity-related differences in drug exposure and/or obesity-induced immunomodulatory activity," the researchers said.

There were several limitations to the study, such as unavailable data on patients' height and problems with data transcription related to patients' BMI.

Marzolini said additional studies are required to clearly define antiretroviral dose requirements in obese patients with HIV, and therapeutic drug monitoring may be a useful tool to tailor treatment in this population.

Catia Marzolini, PharmD, PhD can be reached at the division of infectious diseases and hospital epidemiology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

For more information:

Marzolini C. Abstract #PS3/3. Presented at: 14th European AIDS Conference; Oct. 16-19, 2013; Brussels.

Disclosure: Marzolini reports no relevant financial disclosures.