Emtricitabine; Tenofovir disoproxil fumarate

What it is

Emtricitabine; tenofovir disoproxil fumarate is one tablet holding two nucleos(t)ide analogue reverse transcriptase inhibitors. Both are fake building blocks: when HIV's reverse transcriptase tries to copy its genetic material it incorporates them and the chain stops. Tenofovir disoproxil is a prodrug of tenofovir, and both drugs leave the body through the kidneys, which is where most of their long-term harms come from. The same tablet is used two ways: as part of treatment for people who already have HIV, and as pre-exposure prophylaxis (PrEP) for people who do not.

What the research says

For treatment, this backbone outperformed the older zidovudine-lamivudine backbone: 84% versus 73% reached viral suppression below 400 copies/mL at 48 weeks. For prevention, the evidence is unusually complete and unusually divided. In men who have sex with men and in heterosexual serodiscordant couples it worked - 44% fewer infections in iPrEx, 75% fewer in Partners PrEP, 86% fewer in the open-label PROUD trial where 13 men needed a year of PrEP to avert one infection. In two large trials in African women, VOICE and FEM-PrEP, it did not work at all, and in both, drug was detectable in a minority of samples. The harms are consistent across indications: small but measurable falls in bone density, a modest increase in kidney adverse events, and a boxed warning about hepatitis B flaring when the drug is stopped.

Evidence grade: Well established.

How it works

Drug class: Fixed-dose combination of two nucleos(t)ide analogue reverse transcriptase inhibitors (NRTIs)

Both drugs are decoy versions of the natural building blocks HIV needs to copy its genetic material. HIV's reverse transcriptase enzyme takes them up, and because they lack the chemical handle needed to add the next unit, copying stops. Because the drugs act on an enzyme the virus supplies rather than on human cells, they only work against the virus; and because both are cleared by the kidney, kidney function governs how much stays in the body. (Source 1)

Boxed warning

Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued TRUVADA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue TRUVADA. If appropriate, anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1) ] . TRUVADA used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of TRUVADA for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate TRUVADA for HIV-1 PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed

(Source 2)

What it is used for

• In an open-label randomised trial of 517 treatment-naive adults, this backbone with efavirenz suppressed HIV better than zidovudine-lamivudine with efavirenz (84% versus 73% below 400 copies/mL at 48 weeks) and caused fewer discontinuations for adverse events (4% versus 9%). Evidence: established. (Source 3)
• Three randomised trials in different populations found large reductions: 44% in iPrEx (men and transgender women who have sex with men), 75% in Partners PrEP (heterosexual serodiscordant couples), and 86% in the open-label PROUD trial, where 13 men needed a year of PrEP to prevent one infection. Benefit tracked adherence closely. Evidence: established. (Source 4)
• Two large placebo-controlled trials in African women, VOICE and FEM-PrEP, found no reduction in HIV acquisition, and both were stopped or reported for futility. In both, tenofovir was detectable in only a minority of samples, so the trials cannot separate a drug that does not work in this population from a drug that was not taken. Evidence: disputed. (Source 5)
• In the IPERGAY trial, 400 men took tablets before and after sex rather than daily and had 86% fewer HIV infections than placebo (2 versus 14 infections). It is one trial in one population, participants still took a median of 15 pills a month, and gastrointestinal and renal adverse events were more common than on placebo. Evidence: limited. (Source 6)

Interactions

• Vitamin D and calcium supplements (clinical trial): Because tenofovir disoproxil lowers bone density, supplementation has been studied as a countermeasure. A meta-analysis of seven studies in 703 people taking tenofovir-based regimens found vitamin D plus calcium was associated with higher spine and hip bone density, with a dose-response pattern. These are small studies, mostly not blinded, and the analysis is of bone density rather than fractures. (Source 7)
• Non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, diclofenac and others) (label): High-dose or multiple NSAIDs on top of this combination have caused acute kidney failure in people who had been stable, some needing dialysis. The labelling says to avoid them in anyone at risk of kidney problems. (Source 8)
• Aciclovir, valaciclovir, ganciclovir, cidofovir, adefovir and aminoglycoside antibiotics (label): These drugs leave the body by the same active tubular secretion route as emtricitabine and tenofovir, so taking them together can raise levels of either drug or both, with more risk of kidney injury. (Source 9)
• A fatty meal (pharmacokinetic study): Food raises tenofovir absorption: a high-fat or light meal increased tenofovir exposure by about 35% and peak level by about 15%, and delayed the peak by about three quarters of an hour. Emtricitabine was unaffected, and the tablet is licensed to be taken with or without food. The original efficacy trials were conducted with food. (Source 10)
• Any drug that reduces kidney function (label): Both components are cleared by the kidney, so anything that worsens kidney function raises their blood levels, which in turn raises the risk of tubular injury. This is the mechanism behind most of the clinically important interactions for this tablet. (Source 9)

Stopping it

• There is no dependence or withdrawal syndrome, but stopping is the dangerous moment for one group: people who also have hepatitis B can get a severe flare of hepatitis when the drug is withdrawn, so liver function needs watching for at least several months afterwards and hepatitis B treatment may be needed. (Source 2)
• For prevention, stopping simply removes the protection. In PROUD the group whose PrEP was deferred for a year had 20 HIV infections against 3 in the immediate group, at 9.0 versus 1.2 per 100 person-years, despite 174 courses of post-exposure prophylaxis being prescribed in that deferred group. (Source 11)
• Bone density loss appears reversible in direction: the same literature that finds tenofovir lowers bone density also finds that in PrEP users fracture rates were not increased, and vitamin D with calcium was associated with recovery of bone density in people still taking the drug. (Source 7)

What goes wrong

Tenofovir disoproxil used as PrEP raises the risk of kidney adverse events, though serious events are rare, and the risk concentrates in older people and those whose kidney function is already reduced. (Source 12)

• Systematic review, Moderate certainty.
• Size: 11 randomised trials with 13,523 participants, plus individual participant data on 18,676 people from 15 countries.
• Who: Users of tenofovir disoproxil-based oral PrEP, in trials and in implementation projects.
• How long: Trial durations plus longitudinal follow-up of 14,368 PrEP users.
• Result: Grade 1 or higher kidney adverse events pooled odds ratio 1.49 (95% CI 1.22-1.81); grade 2 or higher 1.75 (0.68-4.49), not statistically significant and rare (13 of 6,764 vs 6 of 6,782); 349 of 14,368 users (2.43%) declined to a creatinine clearance below 60 mL/min.
• Funding: not stated in the abstract (WHO-related guidance analysis)

PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I²=25%)

Tenofovir disoproxil lowers bone mineral density, about twice as much when used for HIV treatment as for PrEP, but pooled PrEP trials did not show more fractures. (Source 13)

• Meta-analysis, Moderate certainty.
• Size: 25 randomised trials from 5,178 screened abstracts.
• Who: People taking tenofovir disoproxil for PrEP, HIV treatment or hepatitis B treatment, compared with people not taking it.
• How long: 48 weeks (plus or minus 4 weeks)
• Result: Lumbar spine mean difference -0.82% (95% CI -1.28 to -0.37) for PrEP and -1.62% (-2.30 to -0.95) for HIV treatment; total hip -0.81% and -1.75%; fractures in five PrEP studies RR 1.12 (95% CI 0.752 to 1.74)
• Funding: not stated in the abstract (PROSPERO CRD#42017070552)

Pooled results from five PrEP studies showed that TDF was not associated with increased fractures compared with no PrEP (RR=1.12, 95% CI=0.752, 1.74, I²=26%).

In the FEM-PrEP trial, nausea, vomiting and raised liver enzymes were all significantly more common on TDF-FTC than on placebo, and more women stopped the drug for liver or kidney abnormalities. (Source 14)

• Randomized trial, Moderate certainty.
• Size: 2,120 women randomised.
• Who: HIV-negative women in Kenya, South Africa and Tanzania.
• How long: Until the trial stopped in April 2011.
• Result: Nausea (P=0.04), vomiting (P<0.001) and raised alanine aminotransferase (P=0.03) all more frequent on TDF-FTC; discontinuation for hepatic or renal abnormalities 4.7% vs 3.0% (P=0.051)
• Funding: independent (US Agency for International Development and others)

The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051).

In the on-demand PrEP trial, gastrointestinal and renal adverse events were roughly twice as common on the drug as on placebo. (Source 6)

• Randomized trial, Moderate certainty.
• Size: 400 participants.
• Who: Men who have condomless anal sex with men.
• How long: Median 9.3 months.
• Result: Gastrointestinal adverse events 14% vs 5% (P=0.002); renal adverse events 18% vs 10% (P=0.03); serious adverse event rates similar.
• Funding: independent (ANRS and others)

In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03).

Creatinine rises were significantly more common on oral TDF-FTC than on placebo in the VOICE trial, even though adherence was low. (Source 5)

• Randomized trial, Moderate certainty.
• Size: 5,029 women.
• Who: Reproductive-age women in South Africa, Uganda and Zimbabwe.
• How long: 5,509 person-years.
• Result: Serum creatinine elevations in 1.3% on oral TDF-FTC vs 0.2% on oral placebo (P=0.004)
• Funding: independent (National Institutes of Health)

Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004).

Stopping the drug can trigger a severe flare of hepatitis B in someone who has that infection, which is why hepatitis B status is checked before starting and liver function monitored for months after stopping. (Source 2)

• Official position, Certainty not rated.
• Size: Not quantified in the labelling.
• Who: People with hepatitis B virus infection taking the combination.
• How long: At least several months after discontinuation.
• Result: Boxed warning requiring close clinical and laboratory monitoring after stopping.
• Funding: manufacturer-generated labelling (position of the FDA-approved label, DailyMed version read 2026-10-01)

Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued TRUVADA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue TRUVADA.

Acute kidney failure and Fanconi syndrome - kidney tubule injury with severe phosphate loss - have been reported with the tenofovir disoproxil component, and the risk rises sharply with NSAIDs. (Source 8)

• Official position, Certainty not rated.
• Size: Not quantified in the labelling.
• Who: People taking the combination, especially those with existing risk factors for kidney dysfunction.
• How long: Reported after initiation of high-dose or multiple NSAIDs in people previously stable.
• Result: Cases requiring hospitalisation and renal replacement therapy.
• Funding: manufacturer-generated labelling (position of the FDA-approved label)

Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Some patients required hospitalization and renal replacement therapy.

Starting PrEP during an undetected acute HIV infection can select for drug-resistant virus, which is why HIV testing is required immediately before starting and at least every three months. (Source 2)

• Official position, Certainty not rated.
• Size: Not quantified in the labelling.
• Who: People starting or continuing the combination for PrEP.
• How long: Testing at least every 3 months during use.
• Result: Drug-resistant HIV-1 variants identified following undetected acute infection.
• Funding: manufacturer-generated labelling (position of the FDA-approved label)

Drug-resistant HIV-1 variants have been identified with use of TRUVADA for HIV-1 PrEP following undetected acute HIV-1 infection.

What the evidence supports

As part of first-line HIV treatment, this backbone achieved viral suppression in more people than the older zidovudine-lamivudine backbone and caused fewer discontinuations. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 517 patients.
• Who: Adults with HIV infection who had not previously received antiretroviral therapy.
• How long: 48 weeks.
• Result: 84% vs 73% below 400 copies/mL (95% CI for difference 4 to 19 percentage points, P=0.002); 80% vs 70% below 50 copies/mL; CD4 rise 190 vs 158 cells/mm3; discontinuation for adverse events 4% vs 9% (P=0.02)
• Funding: not stated in the abstract (open-label study of the manufacturer's regimen, ClinicalTrials.gov NCT00112047)

Through week 48, significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P=0.002).

Daily oral FTC-TDF reduced HIV acquisition by 44% in men and transgender women who have sex with men, and the effect was tied to whether drug was actually detectable in blood. (Source 4)

• Randomized trial, Moderate certainty.
• Size: 2,499 randomised; 3,324 person-years of follow-up.
• Who: HIV-seronegative men and transgender women who have sex with men, in six countries.
• How long: Median 1.2 years, maximum 2.8 years.
• Result: 36 infections on FTC-TDF vs 64 on placebo; 44% reduction in incidence (95% CI 15 to 63; P=0.005); study drug detected in 51% of uninfected but only 9% of infected participants in the active arm.
• Funding: independent (National Institutes of Health and the Bill and Melinda Gates Foundation)

100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005).

In heterosexual serodiscordant couples, daily FTC-TDF reduced HIV-1 incidence by 75%, and it worked in both men and women. (Source 15)

• Randomized trial, High certainty.
• Size: 4,758 couples enrolled, 4,747 followed.
• Who: HIV-1-serodiscordant heterosexual couples in Kenya and Uganda; the seronegative partner was male in 62%.
• How long: Monthly follow-up for up to 36 months.
• Result: 13 infections on TDF-FTC (0.50 per 100 person-years) vs 52 on placebo (1.99 per 100 person-years); relative reduction 75% (95% CI 55 to 87; P<0.001); TDF alone 67% (95% CI 44 to 81)
• Funding: independent (Bill and Melinda Gates Foundation)

13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001)

In an open-label pragmatic trial in English sexual health clinics, immediate PrEP cut HIV infections by 86% and 13 men needed a year of PrEP to avert one infection, with no increase in other sexually transmitted infections. (Source 11)

• Randomized trial, Moderate certainty.
• Size: 544 participants (275 immediate, 269 deferred)
• Who: HIV-negative gay and other men who have sex with men reporting condomless anal sex in the previous 90 days.
• How long: One-year deferral period, quarterly follow-up.
• Result: 3 infections (1.2 per 100 person-years) vs 20 (9.0 per 100 person-years); relative reduction 86% (90% CI 64-96, p=0.0001); absolute difference 7.8 per 100 person-years; number needed to treat 13 (90% CI 9-23); 28 adverse events led to interruption.
• Funding: mixed: MRC Clinical Trials Unit at UCL and Public Health England, with Gilead Sciences (the manufacturer) also named as a funder.

13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection.

Event-driven dosing around sexual activity, which is not an approved schedule, reduced HIV infections by 86% in one trial of men who have sex with men. (Source 6)

• Randomized trial, Low certainty.
• Size: 400 participants enrolled (199 drug, 201 placebo)
• Who: Men who have condomless anal sex with men, in France and Canada.
• How long: Median 9.3 months.
• Result: 2 infections (0.91 per 100 person-years) vs 14 (6.60 per 100 person-years); relative reduction 86% (95% CI 40 to 98; P=0.002); median 15 pills per month in both arms.
• Funding: independent (French National Agency of Research on AIDS and Viral Hepatitis and others)

2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002).

What the evidence does not support

In the largest PrEP trial in African women, neither oral TDF-FTC, nor oral TDF, nor tenofovir vaginal gel reduced HIV acquisition, and adherence was low. (Source 5)

• Randomized trial, High certainty.
• Size: 5,029 women enrolled from 12,320 screened; 5,509 person-years.
• Who: Reproductive-age women in South Africa, Uganda and Zimbabwe.
• How long: 91% retention over 5,509 person-years.
• Result: 312 infections, incidence 5.7 per 100 person-years; effectiveness -4.4% with TDF-FTC (hazard ratio 1.04, 95% CI 0.73 to 1.49); tenofovir detected in only 29% of plasma samples in the TDF-FTC arm.
• Funding: independent (National Institutes of Health)

In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21).

A second trial in African women was stopped early for futility: TDF-FTC did not reduce HIV infection and caused more side effects than placebo. (Source 14)

• Randomized trial, High certainty.
• Size: 2,120 women randomised.
• Who: HIV-negative women in Kenya, South Africa and Tanzania.
• How long: Stopped early in April 2011.
• Result: 33 infections on TDF-FTC (4.7 per 100 person-years) vs 35 on placebo (5.0 per 100 person-years); hazard ratio 0.94 (95% CI 0.59 to 1.52; P=0.81); fewer than 40% had evidence of recent pill use.
• Funding: independent (US Agency for International Development and others)

for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81)

Where the research disagrees

Whether daily oral FTC-TDF prevents HIV in women

• Partners PrEP investigators, Randomised placebo-controlled trial in 4,747 serodiscordant couples with monthly follow-up: "both study medications significantly reduced the HIV-1 incidence among both men and women" (Source 15)
• VOICE investigators, Randomised placebo-controlled trial in 5,029 African women; tenofovir detected in only 29% of plasma samples in the TDF-FTC arm: "In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49)" - no protection at all (Source 5)
• FEM-PrEP investigators, Randomised placebo-controlled trial in 2,120 women, stopped for futility: "Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion." - the trial could not distinguish drug failure from non-adherence (Source 14)

How much the bone density loss matters

• Meta-analysis of 25 randomised trials (2020), Meta-analysis of randomised trials measuring bone mineral density at 48 weeks: "TDF was associated with greater BMD decline when taken as PrEP (lumbar spine: mean difference [MD]=-0.82%, 95% CI=-1.28, -0.37%" and roughly twice that for HIV treatment (Source 13)
• The same meta-analysis, on clinical outcomes, Pooled fracture data from five PrEP trials - underpowered for a rare outcome over 48 weeks: "Pooled results from five PrEP studies showed that TDF was not associated with increased fractures compared with no PrEP (RR=1.12, 95% CI=0.752, 1.74, I²=26%)." (Source 13)

How much

• Reference intake: There is no reference intake for a prescription antiretroviral; the dose is set by a prescriber. The approved US labelling gives one tablet of 200 mg emtricitabine with 300 mg tenofovir disoproxil fumarate once daily for adults, for both HIV treatment and PrEP (position of the FDA-approved label, DailyMed version read 2026-10-01). (Source 16)
• Upper limit: There is no titration and no higher dose: one tablet once daily is both the labelled dose and the labelled maximum for adults, with reduced frequency in renal impairment (position of the FDA-approved label). (Source 16)
• Studied: iPrEx gave a combination of emtricitabine and tenofovir disoproxil fumarate orally once daily against placebo, alongside HIV testing, risk-reduction counselling and condoms. (Source 4)
• Studied: PROUD gave tenofovir disoproxil fumarate 245 mg with emtricitabine 200 mg once daily, either immediately or after a one-year deferral. (Source 11)
• Studied: IPERGAY gave tablets before and after sexual activity rather than daily; participants took a median of 15 pills per month. (Source 6)
• Studied: The HIV treatment trial gave tenofovir disoproxil fumarate with emtricitabine and efavirenz once daily against fixed-dose zidovudine and lamivudine twice daily plus efavirenz. (Source 3)

A common belief, and what the research shows

The belief: PrEP was shown not to work in women, so the drug does not protect women.

What the research shows: The two trials that found nothing, VOICE and FEM-PrEP, both found that most participants were not taking the tablets. VOICE reported that "TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively." FEM-PrEP reported that "Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion." In the trial where adherence was better, Partners PrEP, "both study medications significantly reduced the HIV-1 incidence among both men and women". The honest conclusion is that this drug only protects people who take it, and that daily pill-taking proved much harder to sustain in these trial populations than in the men's trials.

Questions and answers

What is it?

It is one tablet containing two antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, both of which block the enzyme HIV uses to copy its genetic material. It has two separate licensed jobs: as part of combination treatment for people living with HIV, and as pre-exposure prophylaxis for people who do not have HIV but are at risk of it. (Source 1)

What does it do in the body?

Both drugs are imitations of the natural building blocks of DNA. HIV's reverse transcriptase enzyme takes them up while copying the viral genome, and the chain then cannot be extended, so replication stops. Because both are excreted by the kidneys, kidney function controls how much accumulates - which is why kidney injury and phosphate loss are the characteristic harms. (Source 8)

Is it good or bad for you?

For people with HIV it is part of a treatment that works, and for people at substantial risk of HIV it prevents a large share of infections - in the PROUD trial, 13 men needed a year of PrEP to prevent one infection. The costs are real but mostly modest: a small drop in bone density, a measurable but usually mild rise in kidney adverse events, nausea early on. The genuinely dangerous situations are stopping it when you also have hepatitis B, and starting it during an undiagnosed acute HIV infection. (Source 11)

How do you get more of it?

This does not apply as it would for a nutrient: no food or behaviour supplies either drug, and the amount is a fixed once-daily tablet set by a prescriber rather than something to increase. What does change blood levels is food - a meal raises tenofovir exposure by around 35% - and kidney function, which determines how fast both drugs leave the body. (Source 10)

If it is harmful, what reduces it?

When the problem is the drug, the answer studied in the literature is stopping or switching, which is a prescriber's decision - and in one group stopping is itself hazardous, because hepatitis B can flare severely afterwards. For the bone effect specifically, a meta-analysis of seven studies found vitamin D with calcium was associated with recovery of bone density in people still taking tenofovir, rather than requiring the drug to be stopped. (Source 7)

Why might someone be low in it or missing it?

The dominant reason is not taking the tablets. In VOICE, tenofovir was detectable in under a third of plasma samples; in FEM-PrEP, fewer than 40% of women had evidence of recent pill use; and in iPrEx the drug was found in 51% of uninfected participants in the active arm but only 9% of those who became infected. Side effects account for a smaller share: 28 adverse events led to interruption in PROUD, and 4.7% of women in FEM-PrEP stopped for liver or kidney abnormalities. (Source 5)

Which whole foods contain it or feed it?

No whole food contains either drug. Food matters in two ways. A meal, high-fat or light, increases tenofovir exposure by roughly a third, though the tablet is licensed with or without food. And because tenofovir disoproxil lowers bone density, dietary and supplemental calcium and vitamin D have been studied as a countermeasure, with a meta-analysis finding higher bone density in people who took them. (Source 10)

What happens if you do not have it?

For someone with HIV, stopping treatment means the virus replicates again; the comparison in the licensing trial was against another regimen, not against nothing, so the trial cannot quantify no treatment. For prevention, the PROUD trial gives a direct answer: men whose PrEP was deferred for a year had HIV incidence of 9.0 per 100 person-years against 1.2 in those given it immediately, despite post-exposure prophylaxis being available to them. (Source 11)

How can you test for it?

Three kinds of test are involved, and they are reliable to different degrees. An HIV test is mandatory immediately before starting PrEP and at least every three months during it, because starting during an undetected infection breeds resistance. Kidney function - creatinine, estimated creatinine clearance, urine glucose and protein - is checked before and during use. Adherence can be checked by measuring the drug itself: in iPrEx, drug was detected in 51% of uninfected participants on the active arm but only 9% of those who became infected, and detectable levels tracked protection closely. (Source 4)

References

1. DailyMed, U.S. National Library of Medicine (FDA-approved labeling). TRUVADA (emtricitabine and tenofovir disoproxil fumarate) - FDA prescribing information, sections 1.1 and 1.2. 2026. Read the source
2. DailyMed, U.S. National Library of Medicine (FDA-approved labeling). TRUVADA (emtricitabine and tenofovir disoproxil fumarate) - FDA prescribing information, boxed warning. 2026. Read the source
3. The New England journal of medicine. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV.. 2006. PMID 16421366, DOI 10.1056/nejmoa051871. Read the source
4. The New England journal of medicine. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.. 2010. PMID 21091279, DOI 10.1056/nejmoa1011205. Read the source
5. The New England journal of medicine. Tenofovir-based preexposure prophylaxis for HIV infection among African women.. 2015. PMID 25651245, DOI 10.1056/nejmoa1402269. Read the source
6. The New England journal of medicine. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.. 2015. PMID 26624850, DOI 10.1056/nejmoa1506273. Read the source
7. Frontiers in nutrition. Vitamin D and Calcium Supplementation Reverses Tenofovir-Caused Bone Mineral Density Loss in People Taking ART or PrEP: A Systematic Review and Meta-Analysis.. 2022. PMID 35433788, DOI 10.3389/fnut.2022.749948. Read the source
8. DailyMed, U.S. National Library of Medicine (FDA-approved labeling). TRUVADA (emtricitabine and tenofovir disoproxil fumarate) - FDA prescribing information, section 5.3 New Onset or Worsening Renal Impairment. 2026. Read the source
9. DailyMed, U.S. National Library of Medicine (FDA-approved labeling). TRUVADA (emtricitabine and tenofovir disoproxil fumarate) - FDA prescribing information, section 7.1 Drugs Affecting Renal Function. 2026. Read the source
10. DailyMed, U.S. National Library of Medicine (FDA-approved labeling). TRUVADA (emtricitabine and tenofovir disoproxil fumarate) - FDA prescribing information, section 12.3 Pharmacokinetics (Effects of Food on Oral Absorption). 2026. Read the source
11. Lancet (London, England). Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.. 2016. PMID 26364263, DOI 10.1016/s0140-6736(15)00056-2. Read the source
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