Results from a new review of several studies indicate that people who have low levels of drug-resistant HIV in their blood are two to three times more likely to experience treatment failure than people with no detectable drug-resistant HIV.

In particular, a link was found between treatment failure and low levels of HIV resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Based on their results, the review authors stressed the need for laboratory tests that physicians can use to detect trace amounts of drug-resistant HIV in their patients before they start treatment.

“There are more treatment choices than ever for patients with HIV. Once these ultrasensitive tests become available for clinical use, physicians will be able to make more informed decisions on the best treatment regimens for their patients,” said Dr. Jonathan Li, an associate physician at Brigham and Women’s Hospital, instructor in medicine at Harvard Medical School, and lead author of the study.

The authors noted that approximately 1 in 11 patients experience treatment failure that could be prevented using these screening techniques.

Dr. Li also noted that while their results apply to drug resistance specifically against NNRTIs, it is possible that low levels of drug resistance to other drug classes could have similar effects.

“It’s quite possible that minority drug-resistance mutations will have an impact on other classes of antiretroviral medications as well,” said Dr. Li. “These studies are on-going in our laboratory.”

Drug resistance is one of the main causes of antiretroviral drug failure. Individuals are considered resistant to an anti-HIV drug if their viral load (amount of HIV in the blood) does not remain low after treatment and/or testing confirms the presence of an HIV strain that is resistant to one or more classes of antiretroviral drugs.

Since drug resistance can have such a large impact on the efficacy of an antiretroviral drug regimen, people with HIV often undergo resistance testing prior to starting or changing treatment.

Resistance testing involves examining the genes of the HIV in a person’s blood to see if the virus has certain mutations known to make it resistant to particular antiretrovirals. Current drug resistance tests can detect whether these mutations are present in at least 15 percent to 25 percent of the HIV circulating in a person’s blood.

In this study, researchers tested to see whether mutations present in much smaller amounts, in 1 percent or less of the virus in a person’s blood, can affect the probability of treatment failure.

The review included data from 10 studies and a total of 985 participants starting antiretroviral therapy for the first time. For this study, the researchers looked only for mutations that make HIV resistant against NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs).

NNRTI-based regimens, which usually consist of one NNRTI plus two NRTIs, are the most common for people starting treatment for the first time. Sustiva (efavirenz) and Viramune (nevirapine) are both NNRTIs; Atripla (efavirenz/emtricitabine/tenofovir), which contains Sustiva and is the most commonly prescribed initial treatment regimen, is an NNRTI-based regimen.

Participants were followed for a median of 31 months. Researchers measured their CD4 (white blood cell) counts, viral loads (amount of HIV in the blood), and degree of adherence to their antiretroviral regimens. They also performed detailed resistance testing on each participant to determine whether any of their HIV had mutations for drug resistance to NNRTIs or NRTIs.

Results showed that 19 percent of study participants had low levels of drug-resistant HIV in their blood before starting treatment. Further analysis showed that 35 percent of participants with low levels of resistant HIV experienced treatment failure, compared to 15 percent of participants without detectable levels of resistant HIV, a two- to three-fold increase in risk for those with drug-resistant HIV. Treatment failure was defined as a viral load of 200 copies per milliliter or higher after 16 weeks of treatment.

Higher levels of resistant HIV in the blood were linked to a higher risk for treatment failure. However, even when present at extremely low levels (present in less than 0.5 percent of circulating HIV), drug-resistant mutations increased the risk of treatment failure.

The risk of treatment failure was also higher in participants who did not strictly adhere to their medication regimens. For people with low levels of resistant HIV who took their medications at least 95 percent of the time, the risk of treatment failure was 1.5-fold higher than participants without drug-resistant HIV. For participants with drug-resistant HIV who were less than 95 percent adherent, the risk was over 5-fold higher.

The risk of treatment failure was the same for mutations that give resistance against Sustiva and those that give resistance against Viramune.

No link was found between risk of treatment failure and the presence of low levels of NRTI drug resistance mutations. However, only nine participants had HIV with NRTI mutations alone, rather than in combination with NNRTI mutations.

Results also showed that African-American and Hispanic study participants were at higher risk for treatment failure, independent of the presence of low levels of drug-resistant HIV. The authors speculated that this could be due to socioeconomic factors or the different ways in which NNRTIs are metabolized by the body.

Risk of treatment failure was not associated with initial CD4 counts or viral loads.

For more information, please see the study in the Journal of the American Medical Association.