Despite 35 years of prevention and health education efforts, increased access to health care, and improvements in HIV medication efficacy and tolerability, the disease continues to spread across both developed and developing countries. In 2017, almost 40,000 cases of HIV were diagnosed in the United States. The main route of transmission is sexual contact, predominantly in men who have sex with men (MSM).1 It is well documented that if a person living with HIV/AIDS (PLWH) is undetectable (HIV viral load <200 copies/mL), the risk of viral transmission to others is virtually zero.
However, in the United States, just 61% of PLWH are consistently undetectable,2and 91.5% of new HIV infections are transmitted by people who have either not received a diagnosis or not engaged in care.3This continued transmission of HIV illustrates the need for additional tools for prevention.
In July 2012, the FDA approved tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 200 mg/300 mg taken once daily as pre-exposure prophylaxis (PrEP) for individuals at a higher risk of HIV infection. The approval was based on the results of various studies showing PrEP to be highly effective at preventing HIV transmission when used daily.4,5The CDC recommends PrEP for heterosexual men and women who report inconsistent condom use and in a high-prevalence area or network, injection drug users who share equipment, individuals with a sexual partner who is HIV positive, MSM with a recent sexually transmitted infection (STI) diagnosis or who report inconsistent condom use, and those who participate in transactional sex.6TDF/FTC is the first and only FDA-approved nonbarrier method of HIV prevention. Because of the novelty of using a medication to prevent HIV, lack of long-term data and the potential for increased resistance or increase in STI transmission have led to providers using caution with PrEP. However, more recent data continue to support the safety and efficacy of daily TDF/FTC. An analysis of real-world demonstration projects in 16 countries combining more than 8000 individuals showed a <1% HIV acquisition rate and few adverse events.7Populations included in the analysis included heterosexual women, injection drug users, MSM, serodiscordant couples, and transgender women. In the first 5 years of PrEP, about 100,000 individuals have started and about 60,000 individuals are currently taking it.8,9This number is less than the 10% of the individuals who the CDC estimates fit the criteria for being at a higher risk of HIV infection. Although the data show that PrEP implementation is expanding, few of the individuals are people of color or younger than 25—2 populations that are at higher risk of HIV acquisition.8
Results from retrospective studies on real-world use have shown that early patients on daily PrEP have high adherence and motivation for continuing PrEP.10However, a concern of practitioners is that inconsistent PrEP adherence will decrease efficacy and lead to HIV resistance and increased transmission. Pharmacologic modeling analyses predict 96% to 99% protection in rectal tissue after just 4 tablets of TDF/FTC and continued protection with adherence of 4 to 6 tablets per week.11In addition, the inferred risk reduction remained ≥90% for 7 days after discontinuation of a 30-day regimen of daily TDF/FTC.11However, PrEP is not 100% effective, even with perfect adherence. Results of published case reports show HIV acquisition, despite evidence of high adherence. No method of HIV prevention is 100% effective. Therefore, individuals need to be aware of the risks and benefits of each method to make an informed decision.
An important aspect of PrEP use and prescribing is the management of STIs. PrEP effectively reduces HIV transmission but is inactive against other STIs. It is recommended that individuals continue to receive education in safer sex practices, be given access to condoms, and get screened at least every 6 months for STIs, with some data suggesting every 3 months in the MSM population.6Will daily PrEP lead to a decrease in condom use and an increase in STI transmission? Data on real-world PrEP have shown similar STI rates pre- and post-PrEP initiation and suggest that PrEP may not replace other types of safer sex practices.7,10,12-16More long-term data are needed to better understand how certain populations view PrEP and safer sex options and how its use affects sexual behaviors.
Clinicians and prescribers are concerned about the short- and long-term safety risks of PrEP. TDF can reduce renal function and bone mineral density (BMD) in those living with HIV. Is PrEP potentially harmful? A recent meta-analysis of randomized, placebo-controlled PrEP studies demonstrated that the risk of any adverse event or grade 3/4 adverse events was not statistically significantly different in tenofovir-based PrEP compared with placebo.7However, results from a BMD substudy in the iPrEx cohort comprising 498 patients showed a small decrease in hip and spine BMD in the TDF/FTC group at 24 weeks.17,18Fortunately, this did not lead to a difference in bone fracture rates, and BMD recovered within 6 months of the patients discontinuing PrEP.17,18Additionally, PrEP is meant to prevent transmission during a period of high risk. Risk continues to change throughout an individual’s life, and PrEP is not anticipated to be lifelong therapy for many individuals.
Although results from studies have shown that PrEP is safe and effective in many different patient populations, the majority of data are in MSM. Different populations have different routes of transmission for HIV: female genital tissue for heterosexual women, intravenously in injection drug users, and penile and rectal tissues for MSM. Pharmacologic analyses have shown that FTC and TFV have different tissue distribution patterns, with FTC favoring female genital tissue and TFV favoring colorectal tissue.19Additionally, competing nucleotides are lower in colorectal than female genital tissue, suggesting that higher adherence is required to achieve sufficient drug concentrations in vaginal than in rectal tissue. More data are needed to fully understand this issue.
Daily TDF/FTC is the only FDA-approved regimen for PrEP. However, innovative formulations and routes of administration of PrEP that do not rely on daily adherencewould offer further options for HIV protection.On-demand, or event-driven, PrEP is the practice of dosing medication(s) around a risk for transmission such as a sexual encounter. Results from the IPERGAY study and open-label extension showed an 86% to 97% risk reduction when MSM used TDF/FTC around a sexual encounter.13,14Although more data are needed before this can be recommended in practice, this is a potential option for individuals with infrequent episodes of risk.Various delivery methods such as intravaginal rings and long-acting injectable antiretroviral agents are under investigation and showing promise.20,21Subdermal implants have been designed but not tested in clinical trials yet.22,23Additionally, there is a lot of interest in rectal and vaginal microbicides, though trials have been disappointing. Ideally, individuals would have a variety of HIV and STI prevention products—both barrier and nonbarrier forms—that are safe, effective, and available when needed.
Jacob A. Langness, PharmD, BCPS, is a clinical pharmacist specializing in infectious disease and internal medicine at Abbott Northwestern Hospital in Minneapolis, Minnesota. He completed his doctorate of pharmacy at the University of Minnesota and his PGY1 residency at University of Colorado Hospital.