HIV, the AIDS virus (yellow), infecting a human immune cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
In the largest study of its kind to date, researchers at Stanford University School of Medicine and their colleagues have found that worldwide only a limited number of mutations are responsible for most cases of transmission of drug-resistant HIV.
HIV, the virus that causes AIDS, can mutate in the presence of antiviral drugs, and these mutations can be transmitted from one person to the next.
In the new study of more than 50,000 patients in 111 countries, the researchers found a small group of mutations accounted for a majority of the cases of transmission-related resistance to the HIV drugs used to treat infections in resource-limited settings. The results suggest the levels of transmission of drug-resistant strains have not increased globally as much as once feared, said Robert Shafer, MD, professor of medicine at Stanford and principal investigator for the study.
"What we are showing is that the rates of transmitted drug-resistant HIV in the low- and middle-income countries most affected by HIV have increased modestly. The rate of increase in sub-Saharan Africa has been low, and an increase has not been detected in south Asia and Southeast Asia. That's good news," Shafer said.
However, there continues to be an increase in drug resistance because the regimens used by HIV patients in lower-income countries are often not as robust as those used in upper-income countries, and strict adherence to a daily, lifetime regimen of taking the pills is challenging, particularly for people in the poorest parts of the world, he noted.
"It is inevitable that transmitted drug resistance will increase further, so we need to continue ongoing monitoring to ensure successful, long-term treatment outcomes for the millions of people on therapy worldwide," Shafer said.
He said the findings could have important implications for treatment in these hard-hit regions, leading to the possible development of an inexpensive test for key mutations to help determine which drugs should be given to previously untreated patients.
The study will be published online April 7 in PLOS Medicine.
Halting the spread of HIV
Since 2003, the international community has made major strides toward the goal of universal antiretroviral treatment for HIV, with 11.7 million people in low- and middle-income countries now receiving the lifesaving therapy, according to the Joint United Nations Programme on HIV/AIDS. But there has been concern that, with wider availability of these medications, drug resistance could spread and rapidly reverse those gains.
To gauge the extent of the problem, Shafer and his colleagues reviewed HIV sequencing data on 50,870 individuals across the globe, taken from 287 studies published between 2000 and 2013. Nearly 60 medical institutions on five continents contributed data for the study. The researchers analyzed each virus sequence for the presence of 93 mutations previously shown to be indicators of drug resistance.
They found the overall prevalence of transmitted drug resistance ranged from 2.8 percent in sub-Saharan Africa to 11.5 percent in North America. In south Asia and Southeast Asia, the prevalence of transmitted resistance remained unchanged during the decade of expansion in drug treatment. However, many studies from sub-Saharan Africa have shown the prevalence of resistance to be more than 5 percent in recent years, Shafer noted. He said the inevitable increase in transmitted drug resistance could undermine confidence in the ability to treat HIV in low-income regions and potentially dissuade new patients from seeking care.
To avoid that prospect, the study points to the possibility of creating a simple, inexpensive test for the key resistance-related mutations, which could help clinicians pinpoint the drugs likely to be most effective for individual patients. In both Africa and Asia, the researchers identified four specific resistance-related mutations that were associated with the drugs nevirapine and efavirenz. These are among an older, less-expensive class of drugs known as non-nucleoside reverse transcriptase inhibitors, typically used in the developing world as part of a standard, daily regimen.
"The idea of an inexpensive test for key mutations is attractive because if it were used in conjunction with a viral load test [a measure of the amount of virus in a patient's blood], it would allow physicians to know if therapy should be changed and where adherence counseling should be given," Shafer said. Patients who show signs of these mutations could be switched to newer, albeit more costly, drugs known as protease inhibitors, which are less susceptible to resistance, he said.
"You could therefore shut off the flow of drug resistance by using regimens that are less vulnerable to the development of drug resistance in the first place," he said.
Unrelated strains
The study also found that the drug-resistant strains did not come from a single line of resistant viruses, but were distinctly different from each other, suggesting they had been acquired independently and not as a result of a single transmission chain. That contrasts with patterns of resistance in other microbes, such as malaria and tuberculosis, where resistant strains tend to move rapidly among populations, Shafer said. It also contrasts with an emerging pattern of drug resistance in many upper-income countries, where 20 years of HIV therapy have spawned the spread of many highly drug-resistant strains.
"We are finding that the strains being detected in low-income countries are pretty much unrelated to one another. So that suggests these have not yet gained a foothold in the population, and are less often being transmitted among people who have never received the drugs before," Shafer said.
Explore further: The adaptability of pathogens
More information: Rhee S-Y, Blanco JL, Jordan MR, Taylor J, Lemey P, Varghese V, et al. (2015) Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and SequenceLevel Meta-Analysis. PLoS Med 12(4): e1001810. DOI: 10.1371/journal.pmed.1001810
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HIV, the AIDS virus (yellow), infecting a human immune cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
In the largest study of its kind to date, researchers at Stanford University School of Medicine and their colleagues have found that worldwide only a limited number of mutations are responsible for most cases of transmission of drug-resistant HIV.
HIV, the virus that causes AIDS, can mutate in the presence of antiviral drugs, and these mutations can be transmitted from one person to the next.
In the new study of more than 50,000 patients in 111 countries, the researchers found a small group of mutations accounted for a majority of the cases of transmission-related resistance to the HIV drugs used to treat infections in resource-limited settings. The results suggest the levels of transmission of drug-resistant strains have not increased globally as much as once feared, said Robert Shafer, MD, professor of medicine at Stanford and principal investigator for the study.
"What we are showing is that the rates of transmitted drug-resistant HIV in the low- and middle-income countries most affected by HIV have increased modestly. The rate of increase in sub-Saharan Africa has been low, and an increase has not been detected in south Asia and Southeast Asia. That's good news," Shafer said.
However, there continues to be an increase in drug resistance because the regimens used by HIV patients in lower-income countries are often not as robust as those used in upper-income countries, and strict adherence to a daily, lifetime regimen of taking the pills is challenging, particularly for people in the poorest parts of the world, he noted.
"It is inevitable that transmitted drug resistance will increase further, so we need to continue ongoing monitoring to ensure successful, long-term treatment outcomes for the millions of people on therapy worldwide," Shafer said.
He said the findings could have important implications for treatment in these hard-hit regions, leading to the possible development of an inexpensive test for key mutations to help determine which drugs should be given to previously untreated patients.
The study will be published online April 7 in PLOS Medicine.
Halting the spread of HIV
Since 2003, the international community has made major strides toward the goal of universal antiretroviral treatment for HIV, with 11.7 million people in low- and middle-income countries now receiving the lifesaving therapy, according to the Joint United Nations Programme on HIV/AIDS. But there has been concern that, with wider availability of these medications, drug resistance could spread and rapidly reverse those gains.
To gauge the extent of the problem, Shafer and his colleagues reviewed HIV sequencing data on 50,870 individuals across the globe, taken from 287 studies published between 2000 and 2013. Nearly 60 medical institutions on five continents contributed data for the study. The researchers analyzed each virus sequence for the presence of 93 mutations previously shown to be indicators of drug resistance.
They found the overall prevalence of transmitted drug resistance ranged from 2.8 percent in sub-Saharan Africa to 11.5 percent in North America. In south Asia and Southeast Asia, the prevalence of transmitted resistance remained unchanged during the decade of expansion in drug treatment. However, many studies from sub-Saharan Africa have shown the prevalence of resistance to be more than 5 percent in recent years, Shafer noted. He said the inevitable increase in transmitted drug resistance could undermine confidence in the ability to treat HIV in low-income regions and potentially dissuade new patients from seeking care.
To avoid that prospect, the study points to the possibility of creating a simple, inexpensive test for the key resistance-related mutations, which could help clinicians pinpoint the drugs likely to be most effective for individual patients. In both Africa and Asia, the researchers identified four specific resistance-related mutations that were associated with the drugs nevirapine and efavirenz. These are among an older, less-expensive class of drugs known as non-nucleoside reverse transcriptase inhibitors, typically used in the developing world as part of a standard, daily regimen.
"The idea of an inexpensive test for key mutations is attractive because if it were used in conjunction with a viral load test [a measure of the amount of virus in a patient's blood], it would allow physicians to know if therapy should be changed and where adherence counseling should be given," Shafer said. Patients who show signs of these mutations could be switched to newer, albeit more costly, drugs known as protease inhibitors, which are less susceptible to resistance, he said.
"You could therefore shut off the flow of drug resistance by using regimens that are less vulnerable to the development of drug resistance in the first place," he said.
Unrelated strains
The study also found that the drug-resistant strains did not come from a single line of resistant viruses, but were distinctly different from each other, suggesting they had been acquired independently and not as a result of a single transmission chain. That contrasts with patterns of resistance in other microbes, such as malaria and tuberculosis, where resistant strains tend to move rapidly among populations, Shafer said. It also contrasts with an emerging pattern of drug resistance in many upper-income countries, where 20 years of HIV therapy have spawned the spread of many highly drug-resistant strains.
"We are finding that the strains being detected in low-income countries are pretty much unrelated to one another. So that suggests these have not yet gained a foothold in the population, and are less often being transmitted among people who have never received the drugs before," Shafer said.
Explore further: The adaptability of pathogens
More information: Rhee S-Y, Blanco JL, Jordan MR, Taylor J, Lemey P, Varghese V, et al. (2015) Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and SequenceLevel Meta-Analysis. PLoS Med 12(4): e1001810. DOI: 10.1371/journal.pmed.1001810
Medical Xpress on facebook
Related Stories
The adaptability of pathogens
Drug-resistant HIV viruses can spread rapidly. This is the conclusion of a study conducted as part of the SWISS HIV Cohort Study, which is supported by the SNSF. Only the continuous introduction of new drugs can stop the ...
HIV-positive children more likely to develop drug resistance
Children born with HIV are far more likely to develop resistance to antiretroviral drugs than adults, according to a new Tulane University School of Medicine study.
HIV drug resistance creeps higher: WHO
Drug resistance to HIV medicines has been creeping higher in parts of Africa and Asia but is not steep enough to cause alarm, said a survey released by the World Health Organization on Wednesday.
New Stanford list of HIV mutations vital to tracking AIDS epidemic
In a collaborative study with the World Health Organization and seven other laboratories, researchers at the Stanford University School of Medicine have compiled a list of 93 common mutations of the AIDS virus associated ...
Scientists call for increased surveillance as study assessing HIV drug resistance shows rising rates in Africa
New research published online first in the Lancet suggests that drug-resistant HIV has been increasing in parts of Sub-Saharan Africa since the roll-out of antiretroviral therapy nearly a decade ago.
Recommended for you
Providers have mixed feelings about prescribing HIV prevention
Many health care providers across the United States may be reluctant to prescribe an increasingly important prevention approach to some of their patients who are at substantial ongoing risk for HIV. The quarterly ...
Research links HIV to age-accelerating cellular changes
People undergoing treatment for HIV-1 have an increased risk for earlier onset of age-related illnesses such as some cancers, renal and kidney disease, frailty, osteoporosis and neurocognitive disease. But ...
Researchers dramatically improve ART adherence for minority PHLA
Up to 60% of persons living with HIV (PLHA) in the U.S. are neither taking antiretroviral therapy (ART) nor well engaged in HIV primary care, with racial/ethnic minorities more likely to experience barriers to engagement ...
HIV spreads like internet malware and should be treated earlier
A new model for HIV progression finds that it spreads in a similar way to some computer worms and predicts that early treatment is key to staving off AIDS.
Identification of drug combinations that reverse HIV-1 latency
There are almost 40 million people throughout the world living with HIV-1/AIDs. While current antiretroviral therapies are able to reduce the amount of virus in the blood, HIV remains present in a latent ...
HIV can spread early, evolve in patients' brains
The AIDS virus can genetically evolve and independently replicate in patients' brains early in the illness process, researchers funded by the National Institutes of Health have discovered. An analysis of ...
User comments
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