How I Treat Patients at Risk for HIV-1 Infection With Emtricitabine and TAF

Indira Brar, MD

A simple way to evaluate which patients may be optimal candidates for HIV pre-exposure prophylaxis (PrEP) is to consider anyone who is at high risk for the acquisition of HIV infection. The groups that are commonly considered high risk are men who have sex with men, individuals who have a partner who is HIV positive, people with multiple sexual partners, cross-gender women, and individuals who use intravenous drugs.

There are 2 ways infectious disease specialists commonly offer PrEP. The first is in the case of a patient who comes to your clinic and actively requests PrEP. I think this is an easier conversation because the patient has proactively asked you for PrEP — you can then review risk factors and determine if PrEP is indicated. The other conversation that can happen is when the provider is proactive in identifying people who would benefit from PrEP. But how do you do that? One important factor is knowing if they are in a relationship with someone who is HIV positive. In these cases, I would advise providers of primary care to ask them if this partner is receiving medication and if they are virally suppressed. If the partner with HIV has shown viral suppression, the risk for transmission is very low; it is close to zero. But there are situations where HIV transmission may occur and, to add an additional safety net, I advise clinicians to think about offering PrEP.

Another way to approach the topic is to develop the habit of asking patients who they are having sex with: are they sexually active with men, women, or both? This should be followed by a conversation about their sexual preferences. For example, if a patient reports having sex with men, is this patient the receptive partner? If this is confirmed, the risk for acquisition of any kind of infection, including HIV, is higher, and a clinician should start thinking about prescribing PrEP.

It can be stigmatizing for people to be asked if they have multiple sexual partners. Therefore, when asking patients about a history of multiple sexual partners, I highly advise against asking, “Do you have multiple sexual partners?” In my practice, we always ask, “In the past 6 months, have you been sexually active with more than 1 person?” It is better to ask the numbers, using the framework of the past 3 or 6 months, to get a sense of their sexual experiences. If you find that they have had multiple sexual partners, then discuss PrEP with them.

Regarding specific PrEP regimens, there are 2 US Food and Drug Administration (FDA)-approved medications for PrEP. Both are combinations of 2 anti-HIV drugs: emtricitabine and tenofovir disoproxil fumarate (F/TDF), sold under the brand name Truvada®, and emtricitabine and tenofovir alafenamide (F/TAF), sold under the brand name Descovy®.

Candidates for F/TAF as a PrEP regimen are men and transgender women who have sex with men and who are at risk for HIV-1 infection, because this is the population in which the DISCOVER trial ( Identifier: NCT02842086) was carried out. This trial showed that F/TAF was not inferior to F/TDF in men and transgender women who have sex with men and who are at risk for sexually acquired HIV infection.1 The FDA later approved F/TAF for PrEP in adults and adolescents who weigh ≥35 kg.2

So, when would I use F/TAF over F/TDF? The DISCOVER trial further evaluated bone mineral density (BMD) and renal outcomes as secondary outcome measures in a subset of patients. There is some evidence from the DISCOVER clinical trial that extended out to 96 weeks that renal function does not decrease and is marginally better preserved with TAF-based PrEP compared with TDF-based PrEP. However, there is no statistically significant difference between the 2 formulations. So, it is not that renal function or glomerular filtration rates (GFRs) are worsened with the use of TDF but rather that kidney function appears to be preserved better with TAF.

A similar finding was demonstrated regarding BMD. Researchers found that in DISCOVER, there were fewer people who lost >3% of BMD at both the spine and the hip in the TAF treatment group. This BMD finding is probably much more concerning than the GFR, because as clinicians we can closely monitor renal function. Further, if monitoring GFR demonstrates complications, cessation of TDF commonly results in full recovery of renal function. Conversely, BMD is not something we can monitor on a regular basis. Some insurance companies do not approve dual energy x-ray absorptiometry (DXA) scans. As such, bone health is a serious concern even in healthy individuals receiving a TDF-containing regimen for a long enough time and in situations where TAF-based regimens may have clinical utility in preserving bone density.

Another significant advantage of a TAF-containing PrEP regimen, like Descovy, is that it can be used in adults with creatinine clearance <15 mL/min who are receiving chronic hemodialysis.3 This is significant because before this approval, there was no PrEP regimen for patients with creatinine clearance <15 mL/min receiving dialysis, which is a sizable population.

Once a patient is started on PrEP, the focus shifts to adherence to the regimen. All studies of PrEP have shown that adherence is important and that the individuals who do go on to develop HIV infection are commonly those who are nonadherent. In the United States, the approved PrEP regimen is a once-daily pill. It is vital for patients to know that if they want this medication to work and prevent HIV infection, they should be taking their medication every day. Like with any other medication that someone has to take daily, there is a possibility that people will simply forget to take it. There may also be the misconception that if one is not sexually active on given days, then it may be unnecessary to take the medication. What we do know is that TDF can take up to 7 days to reach therapeutic levels. If patients stop taking the medication, and the levels drop off — which happens much more rapidly with TDF than with TAF — then they will have to take it again continuously for a few days before the medication can reach therapeutic levels and thus be protective.

To simplify this information for presentation to patients, I like to show them a graph of how the level of the drug decreases in their blood. Visualization is important for patients and it is much easier for them to see how nonadherence for a certain number of days may affect their protection against HIV. I practice this technique in our clinic, and I believe it would be a worthwhile tactic for clinicians who may not frequently work with PrEP. Peaks, troughs, and steady states of drug levels can be a difficult concept to explain to patients, and a graph allows a clinician to say “look how long it takes for the drug to get to a certain level and then when you do not take it, this is what happens.”

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With regard to harms associated with PrEP regimens, most are small and gastrointestinal or renal in nature. We always counsel patients that there are short-term and long-term side effects when starting a medication. With PrEP, in the short term, these are usually gastrointestinal side effects (most commonly nausea). Gastrointestinal symptoms will resolve over approximately 10 days to 2 weeks. Some people may have diarrhea, but this is also likely to resolve. When presented in this way, most patients seem to be fine with the information regarding the short-term side effects. With regard to long-term side effects of PrEP, we advise patients that there is a small percentage of people who demonstrate PrEP-related negative effects on renal function. To this end, we monitor renal function every 3 months, and if we see any decrease in kidney function, the drug is discontinued.

Regarding clinical follow-up after PrEP is initiated, even with TAF-based PrEP regimens, the recommendation is to check renal function every 3 to 6 months. Every clinician should also check creatinine, creatinine clearance, and urine protein before initiation of PrEP. Clinicians should test HIV-1 infection status before PrEP initiation and then check serial HIV-1 infection status during follow-up, in addition to screening for other sexually transmitted infections, including chlamydia, syphilis, and gonorrhea.

Of note, one message I want to emphasize about HIV testing is that if at any time you are seeing a patient who presents with symptoms consistent with a viral syndrome (fever, rash, headache, myalgia), you need to check them for acute HIV infection, which means obtaining an HIV viral load.


1. Hare CB, Coll P, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presented at: Annual Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 104.

2.  FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic [press release]. Silver Spring, MD: US Food and Drug Administration; October 3, 2019. Accessed February 25, 2020.

3. Descovy® [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2019. Revised December 2019. Accessed February 25, 2020.