The United Nations Programme on HIV/AIDS has facilitated the delivery of antiretroviral medications to 11.7 million people in low- and middle-income countries. However, with wider availability of medications comes the threat of rapid increases and spread of drug-resistance, which would effectively negate gains made by the U.N. and similar organizations.
In order to gauge the current global extent of HIV drug-resistance, researchers at Stanford University School of Medicine and their colleagues analyzed sequencing data from more than 50,000 patients across 111 countries.
The findings from this study were published recently in PLoS Medicine through an article entitled “Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis.”
“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,” said Robert Shafer, M.D., professor of medicine at Stanford and principal investigator on the study.
Unfortunately, drug resistance will persist since patients in lower-income countries are usually not provided the more robust drug regimens as those seen in upper-income countries—this sets up a scenario of low adherence to medication schedules, particularly for the poorest nations.
“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,” stated Dr. Shafer.
In the current study, Dr. Shafer and his colleagues looked at sequencing data from 287 studies published between 2000 and 2013. The sampling data was very broad, coming from approximately 60 medical institutions on five continents. The researchers scanned the sequencing data for the presence of 93 mutations that had been previously shown to be indicative of a drug-resistance phenotype.
Interestingly, the investigators found overall drug-resistance prevalence in sub-Saharan Africa to be 2.8% and 11.5% in North America. The researchers noted that in recent years sub-Saharan Africa has reported drug-resistance rates up to 5%, which may suggest a tipping point, leading to a rapid rise in resistance over the next several years.
In order to combat the rise in resistance, Dr. Schafer and his colleagues suggested the creation of a test for key resistance-related mutations. The researchers pinpointed four resistance-related markers associated with two older, but commonly used drugs, nevirapine and efavirenz.
“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,” Dr. Shafer explained. “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.”
One of the positive results from the Stanford team’s analysis was that drug resistance for HIV did not spawn from a single line of resistant viruses, instead they are distinctly different each other—a sharp contrast to what has been observed for organisms like malaria and tuberculosis, where resistance has spread very rapidly through the population.
“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,” concluded Dr. Shafer.