Resistance mutations persist for many years in untreated HIV-positive people

Christopher Gadd
Published: 25 January 2005

Many untreated HIV-positive patients maintain resistance mutations for many years after infection, according to a large study from the United States published in the 1st February edition of Clinical Infectious Diseases. This supports calls for genotypic testing of all patients before the initiation of antiretroviral therapy to guide treatment choices, the authors argue.

Recent studies of the prevalence of drug resistance in HIV-positive patients have concentrated on acute infection, usually within two years of contracting the virus, or in patients failing their antiretroviral drug regimens. Although resistance is known to have a detrimental effect on the future response to treatment, few studies have addressed the persistence of resistance in patients infected for many years, but who have not started antiretroviral therapy.

“The prevalence of primary HIV antiretroviral resistance in a chronically infected, geographically, racially, and sexually diverse group of patients with moderately advanced HIV disease is around 9% to 11% and appears to be increasing over time,” the investigators report. “These data support routine genotypic resistance testing of all treatment-naïve patients before initiation of antiretroviral therapy.”

Between 1999 and 2001, investigators from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) study team analysed the genetic make-up of HIV from 491 patients randomly selected from the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial.

None of the patients had taken any antiretroviral therapy. Their mean CD4 cell count was 269 cells/mm3 and 31% had a previous AIDS diagnosis, corresponding to an expected infection duration of seven to eight years.

Defining resistance according to the International AIDS Society 2003 guidelines, plus additional mutations at positions 215 and 69 of the reverse transcriptase enzyme, the researchers saw that 57 patients (12%) had at least one resistance mutation. After adjusting this value to account for their sampling method, they estimated that 11% of the cohort had drug-resistant virus (95% confidence interval [CI] 10 – 12%).

They comment: “The persistence of these mutations is of concern, because they increase the chance of secondary transmission of drug-resistant variants.”

The commonest resistance mutations were found at positions 188 (17 patients), 215 (14 patients) and 69 (12 patients) of the reverse transcriptase enzyme. Since the mutation 118I can occur naturally in HIV, the researchers repeated their analysis after excluding this mutation. This caused a small reduction in the estimated prevalence to 9%.

“The 10.8% prevalence of resistance…is similar to the prevalence of 8.3% among persons with recent diagnoses,” they conclude, “and is surprisingly high for a population with advanced disease.

“Both exceed the 5% level suggested as a threshold at which genotypic testing of all persons at baseline before initiation of therapy would be considered cost-effective.”

The investigators estimated the prevalence of nucleoside analogue (NRTI) resistance mutations to be 8%. In contrast, it was 3% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1% for protease inhibitors (PIs), although only ‘primary’ protease mutations were included in the analysis.

“The most prevalent mutations were in the NRTI class,” they conclude. “NNRTI and PI mutations were seen less frequently, possibly reflecting their later introduction into the antiretroviral armamentarium.”

A multiple logistic regression analysis revealed that non-Hispanic white patients were twice as likely to have resistance than African Americans (odds ratio [OR], 2.1, p = 0.03) and that the prevalence of mutations increased by 40% each year (OR 1.4, p = 0.05).

“This implies that the current prevalence may well be higher than that observed during the three years that this study accrued patients,” the authors speculate. “Clinical management of treatment-naïve, chronically HIV-infected patients in the United States will need to address the growing problem of primary HIV drug resistance.”

In contrast, they did not find any association between the mutations and age, sex, injection drug use, CD4 cell count, viral load, previous AIDS-defining conditions or geographic distribution.


Novak RM et al. Prevalence of antiretroviral drug resistance mutations in chronically HIV-infected, treatment-naive patients: implications for routine resistance screening before initiation of antiretroviral therapy. Clin Infect Dis 40: 468-474, 2005.

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.