Transmission of HIV-1 Drug Resistance is On the Rise

Joanne Stekler, MD, MPH, Associate Professor of the Division of Infectious Diseases and Adjunct Associate Professor of Epidemiology and Global Health at the University of Washington

Joanne Stekler, MD, MPH

Drug resistance is increasing among HIV-positive patients, resulting in increasing costs and potentially reduced patient prognosis.

Research from the University of Washington has found that HIV-1 drug resistance can be transmitted to and by antiretroviral (ARV)-naïve patients, findings that emphasize the need for improved standards in care as well as greater research initiatives to develop therapeutic regimens that carry a low risk for resistance transmission.

“The most interesting finding in our data is that the transmitting partner in our partner pairs with drug resistance split into those for whom drug-resistant mutations represented nearly the entire viral population of the transmitter and those for whom drug resistance represented a minority, with those mutations in the former case being uniformly transmitted to the recipient,” study investigator Joanne Stekler, MD, MPH, Associate Professor of the Division of Infectious Diseases and Adjunct Associate Professor of Epidemiology and Global Health at the University of Washington, told MD Magazine. “In the former case, those mutations were uniformly transmitted to the recipient. Although this is not really surprising, this suggests that one major source of transmitted drug resistance on a population level is likely to be clusters of people who have never taken any anti-HIV medications.”

In this cross-sectional study, investigators reviewed observational trial data of 340 patients with primary HIV-1 infection and their partners. Using phylogenetic distance analysis of HIV-1 envelope (env) sequences, the investigators confirmed a total of 36 (72%) transmission partner-pairs. Ultimately, only 31 partner-pairs that were involved in research studies after 1995 were included in this study. Investigators assessed drug resistance mutations in the HIV-1 polymerase gene using 454-pyrosequencing.

Approximately half (48%) of the 25 partner-pairs that had confirmed transmission data after 1995 featured 1—4 drug resistance mutations (median frequency, 6.0% [IQR 1.5%–98.7%, range 1.0%–99.6%]). Each major mutation (n= 10) in 5 transmitters was identified among recipients of resistance (95% CI 69.2%–100%). At the time of the initial study period, all transmitters had no history of ARV use.

According to Stekler, the findings indicated that patients with a history of ARV are still “likely to transmit a drug-resistant variant only if that variant remains the predominant strain in the individualʼs viral population.” In other words, these patients have to present with detectable viral levels and a variant that has minimal impact on fitness cost. “If the variant has a high impact on viral fitness,” added Stekler, “it is likely to be overgrown by more fit viruses.”

“This [study] is an important concept for understanding how drug resistance impacts pre-exposure prophylaxis (PrEP) programs,” said Stekler. “The mutations associated with resistance to the 2 medications in PrEP are generally associated with high fitness cost, so if someone acquires drug resistance while taking PrEP imperfectly, these mutations are likely to be overgrown by more fit variants and less likely to be transmitted unless there is ongoing selection pressure (ie, someone doesn't get tested for HIV regularly and continues taking PrEP and not ARV treatment.)”

The study, "Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort" was published in PLOS Medicine.