- ACRONYMS AND DEFINITIONS
- FTC - an abbreviation for emtricitabine
- F/TAF - Emtricitabine + tenofovir alafenamide fumarate (Descovy®)
- F/TDF - Emtricitabine + tenofovir disoproxil fumarate (Truvada®)
- HIV - Human immunodeficiency virus
- MSM - Men who have sex with men
- NAT - Nucleic acid test
- NPEP - Nonoccupational post-exposure prophylaxis
- OPEP - Occupational post-exposure prophylaxis
- PEP - Post-exposure prophylaxis
- PrEP - Pre-exposure prophylaxis
- STI - Sexually transmitted infection
- ULN - Upper limit of normal
- HIV RISK
- Overview
- The first case of AIDS was reported in 1981, and in 1983, the human immunodeficiency virus (HIV) was determined to be the cause. Since that time, more than 700,000 people in the U.S have died of AIDS. It's estimated that 1.2 million people in the U.S. are currently living with HIV, and 13% of these individuals (156,000 people) are unaware that they are infected. The annual rate of new HIV cases in the U.S. is trending down, with 34,800 new cases being diagnosed in 2019 compared to 41,200 in 2012.
- The risk for HIV is heterogeneous, with people of different sex, race, age, and sexual preference being affected disproportionately. The table below gives a breakdown of which groups make up the annual percentage of new cases, and the second table provides the estimated risk by exposure type.
Annual new cases of HIV in the U.S. | |
---|---|
Group | % of new cases |
Sex | |
Men (overall) | 81% |
Men (gay and bisexual) | 70% |
Women | 18% |
Age | |
Age 13 - 24 years | 21% |
Age 25 - 34 years | 40% |
Age 35 - 44 years | 20% |
Race | |
Black | 41% |
Hispanic | 29% |
White | 25% |
High-risk behavior | |
People who inject drugs | 10% |
Estimated risk of acquiring HIV by exposure type | |
---|---|
Exposure type | Rate of HIV acquisition per 10,000 exposures |
Parenteral | |
Blood transfusion | 9,250 |
Needle sharing during injection drug use | 63 |
Percutaneous (needlestick) | 23 |
Sexual | |
Receptive anal intercourse | 138 |
Receptive penile-vaginal intercourse | 8 |
Insertive anal intercourse | 11 |
Insertive penile-vaginal intercourse | 4 |
Receptive oral intercourse | low |
Insertive oral intercourse | low |
Other | |
Biting | Negligible |
Spitting | Negligible |
Throwing body fluids (including semen or saliva) | Negligible |
Sharing sex toys | Negligible |
- WHOM TO TREAT
ORAL PREP CRITERIA (CDC 2021) |
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Sexually-active adults and adolescents weighing at least 77 lbs (35 kg) |
Sexual history - anal or vaginal sex in past 6 months and any of the following:
Clinical eligibility - must meet all the following:
|
People who inject drugs that share injection equipment and/or have HIV-positive injecting partners |
Must meet all the following:
|
INJECTABLE PREP CRITERIA (CDC 2021) |
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Sexually-active adults |
Sexual history - anal or vaginal sex in past 6 months and any of the following:
Clinical eligibility - must meet all the following:
|
People who inject drugs that share injection equipment and/or have HIV-positive injecting partners |
Must meet all the following:
|
NPEP RECOMMENDATIONS (CDC 2016) |
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NPEP is recommended if all of the following are met:
NPEP is not recommended (regardless of source HIV status) if any of the following are true:
|
- OPEP recommendations
- The University of California at San Francisco (UCSF) provides up-to-date recommendations on HIV OPEP at the link below
- They also offer free, rapid expert consultation by phone - UCSF consultation
- LAB TESTING
- HIV testing definitions
- HIV-1 and HIV-2 - HIV is divided into two main genotypes, HIV-1 and HIV-2. HIV-1 accounts for the vast majority of infections, and > 99.9% of HIV infections in the United States are of the HIV-1 type. HIV-2 is most commonly seen in West Africa and is very rare in the U.S. (< 0.03% of all infections).
- HIV-1 p24 antigen - HIV-1 p24 antigen is a core nucleocapsid viral protein that becomes detectable in the blood about 14 days after HIV infection; HIV antibodies do not appear until around day 22. HIV-1 p24 antigen testing was added to fourth-generation HIV screening tests to help detect infections before antibodies appear.
- HIV-1/2 antibody/antigen tests (fourth-generation tests) - HIV-1/2 antibody/antigen tests detect HIV antibodies (IgM and IgG) and HIV-1 p24 antigen. HIV antibodies appear around 22 days after infection, and HIV-1 p24 antigen is detectable about 14 days after infection. In the case of a positive test, most assays do not report which component of the test (antibody or antigen) was positive.
- HIV-1/HIV-2 antibody differentiation test - The HIV-1/HIV-2 antibody differentiation test is performed on positive HIV-1/2 antibody/antigen samples to determine which type of HIV antibody (HIV-1 or HIV-2) is present. If the results of this test are negative or indeterminate, further testing with HIV-1 NAT is recommended.
- HIV-1 nucleic acid test (NAT) - HIV-1 nucleic acid tests directly detect HIV RNA in the blood, and results may be qualitative or quantitated in copies/ml. HIV RNA becomes detectable by NAT about 10 days after infection. NATs for HIV-2 are not widely available.
- Rapid HIV tests - a number of rapid HIV tests are available that can be performed in an office setting and provide results in minutes. These tests detect antibodies (IgM and IgG) to HIV-1/2, and some also include HIV-1 p24 detection. Most tests are performed on a fingerstick blood sample, and a few can be used with saliva. Fingerstick blood samples are preferred over mouth swabs because antibody concentrations are lower in saliva. Test sensitivities are > 99% for infections that occurred more than 4 weeks prior. For infections within the prior 4 weeks, plasma testing is more sensitive. See CDC HIV test assays and CDC CLIA-waived tests for more. [3]

HIV screening test interpretation | |||
---|---|---|---|
HIV 1/2 antigen antibody test |
HIV 1/2 antibody differentiation |
HIV-1 NAT | Interpretation |
Negative | NP | NP | Negative |
Positive | HIV-1 (+) HIV-2 (-) |
NP | HIV-1 positive |
Positive | HIV-1 (-) HIV-2 (+) |
NP | HIV-2 positive |
Positive | HIV-1 (+) HIV-2 (+) |
NP | HIV positive (untypable) |
Positive | HIV-1/2 negative or indeterminate |
Positive | Acute HIV-1 infection |
Positive | HIV-1/2 negative or indeterminate |
Negative | Negative for HIV-1 ✝ |
Oral PrEP Lab Recommendations (CDC 2021) |
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Initial visit
|
Treatment monitoring
|
Injectable PrEP Lab Recommendations (CDC 2021) |
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Initial visit
|
Treatment monitoring
|
NPEP Lab Recommendations (CDC 2016) |
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Initial testing
4 - 6 weeks after exposure
3 months after exposure
6 months after exposure
|
- TREATMENT REGIMENS
- Oral daily PrEP
- Men and transgender women
- Emtricitabine + tenofovir alafenamide fumarate (Descovy®) - one tablet once daily
- OR
- Emtricitabine + tenofovir disoproxil fumarate (Truvada®) - one tablet once daily
- All others
- Emtricitabine + tenofovir disoproxil fumarate (Truvada®) - one tablet once daily [1]
- As needed PrEP (2-1-1 regimen)
- As needed PrEP is only recommended as an option for MSM who have sex less than once weekly and can anticipate sex. Patients should only be given 30 pills, with follow-up and HIV testing required before a refill.
- Dosing: F/TDF (Truvada®) 2 pills in the 2 - 24 hours before sex (closer to 24 hours preferred) followed by 1 pill 24 hours after the initial dose, and 1 pill 48 hours after the initial dose
- Additional sexual events:
- If sex occurs on the consecutive day after completing the 2-1-1 doses, take 1 pill per day until 48 hours after the last sexual event
- If a gap of < 7 days occurs between the last pill and the next sexual event, resume 1 pill daily
- If a gap of ≥ 7 days occurs between the last pill and the next sexual event, start again with 2 pills [1]
- Injectable PrEP
- Cabotegravir (Apretude®) 600 mg IM initially, followed by 600 mg one month later, and then 600 mg every 2 months thereafter
- Cabotegravir is given intramuscularly in the gluteal muscle by a healthcare provider
- An oral lead-in phase may be used to assess patient tolerability of cabotegravir
- Lead-in phase dosing: Cabotegravir (Vocabria) 30 mg tablet once daily for 28 days before starting injections
- See cabotegravir dosing for complete dosing information (e.g. missed injections, etc.) [1]
NPEP treatment regimens (CDC 2016) |
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Adults and adolescents ≥ 13 years, including pregnant women, with CrCl ≥ 60 ml/min
|
Adults and adolescents ≥ 13 years with CrCl ≤ 59 ml/min
|
Zidovudine dosing
Lamivudine dosing
|
- OPEP recommendations
- The University of California at San Francisco (UCSF) provides up-to-date recommendations on HIV OPEP at the link below
- They also offer free, rapid expert consultation by phone - UCSF consultation
- TRUVADA® AND DESCOVY®
- Overview
- Truvada and Descovy are the two treatments approved for oral PrEP. Both therapies contain the HIV-1 reverse transcriptase inhibitors emtricitabine and tenofovir. The difference between the pills lies in the tenofovir component; Truvada contains tenofovir disoproxil fumarate (TDF), and Descovy contains tenofovir alafenamide (TAF). TDF and TAF are metabolized to the same active component, tenofovir diphosphate, but TAF is transported much more rapidly into peripheral blood mononuclear cells (PBMC), reducing plasma tenofovir exposure by 90%, relative to TDF, and possibly decreasing the risk of renal toxicity.
- Truvada® dosing (emtricitabine + tenofovir disoproxil fumarate, F/TDF)
- Dosage form: each tablet contains 200 mg of emtricitabine and 300 mg of tenofovir DF (equivalent to 245 mg of tenofovir disoproxil)
- Dosing: one tablet once daily with or without food
- Kidney disease: do not use if CrCl < 60 ml/min
- Approved for adults and adolescents weighing at least 77 lbs (35 kg) [4]
- Cost: Generic available | less than $50/month
- Descovy® dosing (emtricitabine + tenofovir alafenamide, F/TAF)
- Dosage form: tablet comes in two strengths. The dose approved for PrEP contains 200 mg of emtricitabine and 25 mg of tenofovir alafenamide.
- Dosing: one tablet (200/25 mg) once daily with or without food
- Kidney disease:
- CrCl ≥ 30 ml/min: no dose adjustment necessary
- CrCl 15 - 29 ml/min: not recommended
- CrCl < 15 ml/min: do not use if not receiving chronic hemodialysis. If receiving hemodialysis, administer dose on days of hemodialysis after completion of dialysis.
- Approved for adults and adolescents weighing at least 77 lbs (35 kg)
- Cost: No generic | more than $150/month
- Efficacy
- Men and transgender women who have sex with men - in a study involving 2499 HIV-negative MSM who were followed for a median of 1.2 years, Truvada-treated patients had an HIV incidence of 2.9% compared to 5.1% in placebo-treated patients (relative risk reduction 44%). [PMID 21091279]
- Heterosexual discordant couples - in a study involving 4747 HIV-1–serodiscordant heterosexual couples who were followed for a median of 23 months, seronegative Truvada-treated patients had an annual HIV incidence of 0.5% compared to 1.99% in placebo-treated patients (relative risk reduction 75%). [PMID 22784037]
- People who inject drugs - in a study involving 2413 injection drug users who were followed for an average of 4 years, TDF-treated patients had an annual HIV incidence of 0.35% compared to 0.68% in placebo-treated patients (relative risk reduction 49%). [PMID 23769234]
- Truvada vs Descovy - in the DISCOVERY trial that compared Truvada to Descovy in 5387 high-risk MSM, Descovy was found to be noninferior to Truvada for the prevention of HIV infection. [PMID 32711800]
Side effect | Descovy (N=2694) |
Truvada (N=2693) |
---|---|---|
Diarrhea | 5% | 6% |
Nausea | 4% | 5% |
Headache | 2% | 2% |
Fatigue | 2% | 3% |
Abdominal pain | 2% | 3% |
- Precautions
- Hepatitis B virus (HBV) - severe exacerbations of hepatitis B, including liver decompensation and failure, have occurred in HBV-infected patients who discontinued Truvada. Test for HBV before therapy and monitor HBV-infected patients closely for several months when discontinuing Truvada or Descovy. HBV therapy may be appropriate in some patients, and uninfected patients should be offered HBV vaccination.
- HIV infection - Truvada and Descovy should only be given to patients who are HIV negative. Patients who are HIV infected or acquire HIV during therapy may develop HIV resistance if only receiving Truvada or Descovy. See lab monitoring for recommendations on screening for HIV infection.
- Renal toxicity - renal toxicity, including acute renal failure and Fanconi syndrome, has been reported in patients receiving Truvada and TAF-containing products. Descovy causes less systemic tenofovir exposure than Truvada (see overview), and this may lower the risk of renal toxicity. In the 48-week DISCOVER trial that compared Truvada (N=2693) to Descovy (N=2694), the average creatinine clearance (CrCl) decreased by 2.3 ml/min in Truvada-treated patients and increased by 1.8 ml/min in Descovy-treated patients. Urine protein to creatinine ratio increases above 200 mg/g occurred in 2% of Truvada-treated patients and 1% of Descovy-treated patients. No cases of proximal renal tubulopathy were seen in either group, and one case of Fanconi syndrome was seen in the Truvada group. [PMID 32711800] Nephrotoxic drugs, including NSAIDs, may increase the risk of renal toxicity. If a significant decrease in CrCl occurs during therapy, the risks and benefits of continued oral PrEP should be evaluated.
- Bone loss and mineralization defects (Truvada) - in studies, patients treated with TDF-containing drugs have had a slight decrease in bone mineralization when compared to other therapies. The mechanism of this effect is unclear but may be related to altered osteoclast/osteoblast activity and/or renal effects (e.g. hypophosphatemia, altered vitamin D metabolism). In the DISCOVER trial, a subgroup of men treated with Truvada (N=159) underwent BMD testing at baseline and 48 weeks. BMD decreased by about 1 - 2% in Truvada-treated patients when compared to Descovy-treated patients. There was no difference in fracture risk between the groups. [PMID 32711800] Given the small effect, the CDC guidelines do not recommend routine BMD screening before or during PrEP. Patients at increased risk of osteoporosis may want to avoid Truvada.
- Lactic acidosis/Severe Hepatomegaly with Steatosis - rare cases of lactic acidosis and severe hepatomegaly with steatosis have been reported in patients receiving emtricitabine- and/or TDF-containing drugs. Truvada or Descovy should be discontinued in patients who develop signs of lactic acidosis and/or pronounced hepatotoxicity, including hepatomegaly and steatosis, even in the absence of marked transaminase elevations.
- Pregnancy - data from Truvada and Descovy pregnancy exposure registries have shown no significant increase in the risk of major birth defects. Likewise, animal toxicology studies also found no adverse developmental effects. A trial published in 2023 that randomized pregnant women to Truvada at 14 to 28 weeks gestation found no increased risk of preterm birth or small for gestational age infants. [PMID 36746169]
- Kidney disease - see Truvada dosing and Descovy dosing above
- Liver disease
- Child-Pugh A/B: no dose adjustment necessary
- Child-Pugh C: has not been studied [4]
Truvada Drug Interactions |
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Contraindicated drugs
|
Drug interactions
|
Relevant drugs that do not interact with Truvada
|
Descovy Drug Interactions |
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Contraindicated drugs
|
Drug interactions
|
Relevant drugs that do not interact with Descovy
|
- CABOTEGRAVIR (APRETUDE®)
- Overview
- Cabotegravir is an HIV integrase inhibitor that is FDA-approved for PrEP. It is administered as a gluteal intramuscular injection by a healthcare professional.
- Dosing
- Dosage form: single-dose 600 mg/3 ml vial. Store at room temp.
- Dosing: 600 mg IM initially, followed by 600 mg one month later, and then 600 mg every 2 months thereafter. Injections may be given up to 7 days before or after their scheduled date. Cabotegravir is given intramuscularly in the gluteal muscle by a healthcare provider.
- Injection site reactions: injection site reactions are common with cabotegravir. Reactions (pain, tenderness, induration, nodules) are typically mild to moderate, last only a few days, and lessen after the first 2 - 3 injections. Patients can manage reactions by taking NSAIDs and applying warmth (e.g. heating pad, warm compress) to the injection site.
- Missed doses:
- Planned missed injections: If an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, oral cabotegravir 30 mg once daily may be taken for a duration of up to 2 months to replace 1 missed scheduled every-2-month injection. The first dose of oral cabotegravir should be taken approximately 2 months after the last injection. Resume injections on the day oral dosing completes or within 3 days thereafter. If more than 2 months of oral cabotegravir is needed, an alternative oral PrEP regimen is recommended.
- Second injection: If the time since the first injection is ≤ 2 months, administer the second dose ASAP and then continue every-2-month schedule. If the time since the first injection is > 2 months, restart the initial dosing schedule.
- Third and all subsequent injections: If the time since the prior injection is ≤ 3 months, administer the missed dose ASAP and then continue with every-2-month schedule. If the time since the prior injection is > 3 months, restart the initial dosing schedule.
- Oral lead-in phase:
- An oral lead-in phase may be used to assess patient tolerability of cabotegravir
- Lead-in phase dosing: Cabotegravir (Vocabria®) 30 mg tablet once daily for 28 days. Initiate injection on the last day of the oral lead-in phase or within 3 days thereafter. The injection schedule is the same as without an oral lead-in. [4]
- Efficacy
- Men and transgender women who have sex with men - in a study involving 4566 MSM who were followed for a median of 1.24 years, the annual incidence of HIV infection was 0.41% in cabotegravir-treated patients and 1.22% in Truvada-treated patients (p=0.0003 for superiority). [PMID 34379922]
- High-risk women - in a study involving 3224 high-risk women who were followed for a median of 1.4 years, the annual incidence of HIV infection was 0.2% in cabotegravir-treated patients and 1.85% in Truvada-treated patients (p<0.0001 for superiority). [PMID 35378077]
Side effect | Cabotegravir (N=2281) |
Truvada (N=2285) |
---|---|---|
Injection site reactions ✝ | 82% | 35% (placebo injection) |
Diarrhea | 4% | 5% |
Headache | 4% | 3% |
Pyrexia | 4% | <1% |
Fatigue | 4% | 2% |
Sleep disorders | 3% | 3% |
Nausea | 3% | 5% |
Dizziness | 2% | 3% |
- Precautions
- HIV infection - Cabotegravir should only be given to patients who are HIV negative. Patients who are HIV infected or acquire HIV during therapy may develop HIV resistance if only receiving cabotegravir. The long half-life of cabotegravir injections (average 5 - 12 weeks) should also be taken into account when considering the risk of resistance development in noncompliant patients. See lab monitoring for recommendations on screening for HIV infection.
- Hypersensitivity reactions - hypersensitivity reactions, including severe skin reactions with systemic features, hepatitis, eosinophilia, and angioedema, have been reported with other HIV integrase inhibitors. An oral lead-in phase may help identify patients who are at risk for these reactions. If symptoms develop, patients should be monitored closely, including liver transaminases, and cabotegravir should be stopped.
- Hepatotoxicity - rare cases of hepatotoxicity have been reported in patients receiving cabotegravir. In two large trials (see efficacy), the incidence of ALT/AST elevations ≥ 5 X ULN was similar between cabotegravir-treated patients and Truvada-treated patients (0 - 3%). The CDC does not recommend routine liver function monitoring during cabotegravir therapy.
- Depressive disorders - depressive disorders, including suicide ideation and attempt, have been reported in patients receiving cabotegravir. Monitor patients for depressive symptoms and consider the possible role of cabotegravir if they develop. [4]
Cabotegravir Drug Interactions |
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Contraindicated drugs
|
Drug interactions
|
Relevant drugs that do not interact with cabotegravir
|
- NPEP MEDICATIONS
Quick Prescribing Guide for NPEP Meds |
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F/TDF (Truvada®)
|
Raltegravir (Isentress®) [Prescribing information]
|
Dolutegravir (Tivicay®) [Prescribing information]
|
Zidovudine (Retrovir®) [Prescribing information]
|
Lamivudine (Epivir®) [Prescribing information]
|
Darunavir (Prezista®) [Prescribing information]
|
Ritonavir (Norvir®) [Prescribing information]
|
- ACUTE HIV SYMPTOMS
- Overview
- Symptoms of acute HIV occur within 2 - 4 weeks of infection and can last anywhere from a few days to several weeks; some infections are asymptomatic. The table below gives the incidence of common symptoms.
Symptoms of acute HIV infection | |
---|---|
Symptom | % affected |
Fever | 75% |
Fatigue | 68% |
Myalgia | 49% |
Skin rash ✝ | 48% |
Headache | 45% |
Pharyngitis | 40% |
Cervical adenopathy | 39% |
Arthralgia | 30% |
Night sweats | 28% |
Diarrhea | 27% |
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- 1 - Preexposure prophylaxis for the prevention of HIV infection in the United States – 2021 update, CDC
- 2 - Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016, CDC
- 3 - Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations, CDC
- 4 - Manufacturer's prescribing information