- In rare cases, PrEP can fail if a person is infected with a drug-resistant strain of HIV
- A new study found that resistance to the drugs in PrEP is very uncommon in Canada
- The findings provide reassurance that PrEP is highly effective at preventing HIV
Pre-exposure prophylaxis (PrEP) is the use of medication on an ongoing basis (usually daily) by an HIV-negative person to reduce the risk of HIV transmission. People on PrEP take a combination of two HIV drugs—tenofovir and emtricitabine. PrEP is a highly effective prevention strategy when taken as prescribed. Most of the time when a person who is taking PrEP gets HIV, it is because the person was not taking their pills as prescribed. When people miss too many doses of PrEP, drug levels in the blood may not be high enough to prevent HIV infection.
Although it happens rarely, some people have acquired HIV while taking PrEP as prescribed. In most of these cases, the person was exposed to a strain of HIV that was resistant to one or both of the medications in PrEP, allowing for HIV infection to occur. In order to better understand the risk of HIV transmission due to resistance, it is important to understand the prevalence and incidence of resistance to tenofovir and emtricitabine in people living with HIV.
A recent study examining a large cohort of people with HIV on treatment in Canada found that resistance to tenofovir and emtricitabine in this group was low. This low rate of tenofovir and emtricitabine resistance provides reassurance that potential exposure to HIV that is resistant to PrEP drugs among people on PrEP in Canada would likewise be low.
The study used data from the Canadian Observational Cohort (CANOC), a collaboration combining data from cohorts of people with HIV from sites across Canada. Overall, CANOC participants:
- started HIV treatment after January 1, 2000,
- had no previous experience with HIV treatment before this time (in other words, they were treatment-naïve), and
- are 18 years of age of older.
The analysis for the current study was limited to 6,622 participants who started HIV treatment between 2006 and 2014 at CANOC sites with complete data on drug resistance testing. The start of this period reflects the introduction of resistance testing recommendations in U.S. treatment guidelines, as well as the uptake of tenofovir-based treatment regimens in Canada.
The average profile of the study participants was as follows:
- 84% were male, 16% were female
- age – 40 years old
- duration of follow-up after starting treatment – 3.8 years
The study looked at resistance to tenofovir and emtricitabine before starting HIV treatment and over time after starting treatment.
Drug resistance before starting treatment
Drug resistance before starting treatment was determined through genotype resistance testing. Of the 5,428 participants with genotype test results, 83 (1.5%) had HIV that was resistant to tenofovir and 21 (0.4%) had HIV that was resistant to emtricitabine.
Development of drug resistance after starting treatment
The development of drug resistance after starting treatment was measured through drug resistance testing. The number of participants who developed resistance to tenofovir or emtricitabine and the cumulative incidence of participants with drug resistance was calculated at one, three and five years on treatment.
Of the 6,539 participants who did not have resistance to tenofovir before starting treatment, the following numbers of people developed resistance at each interval:
- one year on treatment – 16 developed resistance
- three years on treatment – 29 developed resistance
- five years on treatment – 34 developed resistance
The cumulative incidence of resistance to tenofovir was 0.27% at one year, 0.55% at three years and 0.70% at five years.
Of the 6,601 participants who did not have resistance to emtricitabine before starting treatment, the following numbers of people developed resistance at each interval:
- one year on treatment – 74 developed resistance
- three years on treatment – 133 developed resistance
- five years on treatment – 159 developed resistance
The cumulative incidence of resistance to emtricitabine was 1.2% at one year, 2.5% at three years and 3.3% at five years.
Implications for people on PrEP
This study found low rates of drug resistance to tenofovir and emtricitabine in a large cohort of people with HIV, both before starting treatment and over time after starting treatment. Understanding the rate of drug resistance to tenofovir and emtricitabine among people with HIV provides additional context for the potential of HIV transmission among people on PrEP.
Low rates of drug resistance to tenofovir and emtricitabine among people on HIV treatment in Canada suggests that the potential impact of drug resistance on HIV transmission among people on PrEP would likewise be low. While this indirect measure is informative, additional research would be needed for more direct conclusions.
- Knox D, Anderson PL, Harrigan PR, Tan DHS. Multidrug-resistant HIV-1 infection despite preexposure prophylaxis. New England Journal of Medicine. 2017; 376(5): 501–2.
- Markowitz M, Grossman H, Anderson PL, Grant R, Gandhi M, Horng H, et al. Newly acquired infection with multidrug-resistant HIV-1 in a patient adherent to preexposure prophylaxis. Journal of Acquired Immune Deficiency Syndromes. 2017; 76(4): e104–6.
- Younger J, Raboud J, Szadkowski L, Harrigan R, Walmsley S, Bayoumi AM, et al. Tenofovir and emtricitabine resistance among antiretroviral-naive patients in the Canadian Observational Cohort Collaboration: Implications for PrEP. Antiviral Therapy. 2019 Mar 15; in press.