How to “PrEP” for HIV Prevention in Women

Case Report

A 30-year-old African American woman with history significant only for well-controlled hypertension presents to clinic for intrauterine device placement. She is in a long-term monogamous relationship with a man who is positive for human immunodeficiency virus (HIV). She is happy in her relationship, although anxious about contracting HIV. He is currently on antiretroviral therapy (ART), and his viral load is undetectable most of the time, although admittedly he had a viral load of 350 copies/mL at one point earlier this year. They use condoms “most of the time” for sexual intercourse. She had a rapid HIV test 1 month ago, which was negative. While waiting to get tested, she saw a pamphlet on HIV pre-exposure prophylaxis (PrEP) and would like to discuss if taking medication can help her remain HIV negative. She had routine screening laboratory work about 6 months ago and was told that all was normal. She takes lisinopril 20 mg daily and no other medications. What would you advise this patient?

Discussion

About 36 million adults worldwide are infected with the HIV. ¹ Although the number of newly diagnosed HIV infections is declining globally, the number of people living with HIV continues to increase because of improved ART. According to the Centers for Disease Control and Prevention (CDC), 24% of new HIV infections in the United States in 2013 were in women. ² Heterosexual contact is the primary mode of HIV transmission to women. ² HIV disproportionally impacts African American women; although they make up ∼12% of the U.S. female population, they account for an estimated 64% of the HIV infections in U.S. women. ²

HIV prevention requires a multifaceted approach inclusive of behavioral and biomedical interventions. PrEP is the strategy of administering ART to uninfected individuals to help prevent HIV. ³ This is akin to taking the oral contraceptive pill to prevent pregnancy. Currently, the daily fixed dose combination tablet of tenofovir 300 mg and emtricitabine 200 mg, sold as trade name Truvada, is the only Food and Drug Administration-approved medication for PrEP. Daily oral Truvada has been shown to be safe and effective in reducing the risk of sexual HIV acquisition in adults. ³ PrEP should be part of a comprehensive approach to HIV prevention. PrEP does not need to be delivered by a multidisciplinary care team; however, persons receiving PrEP should receive risk reduction counseling, be encouraged to use condoms, and undergo HIV and sexually transmitted infections (STIs) screening. Per the CDC, routine HIV testing should be performed every 3 months and STIs screening should be performed every 6 months ³ ; STI testing should also be performed when a person is symptomatic in the interim. It should be emphasized to women that HIV PrEP does not protect against STIs or pregnancy.

Tenofovir and emtricitabine are ARTs known as nucleoside reverse transcriptase inhibitors. These medications work by preventing the HIV viral RNA from being converted to HIV DNA. In order for PrEP to be effective, there must be adequate drug levels before exposure to HIV occurs. Tenofovir concentrates 10–100 times more in rectal tissue than in cervicovaginal tissue, ⁴ whereas emtricitabine values have been shown to be 140–170 times higher in female genital tract tissue than in rectal tissue. ^5,6 This tissue-specific data have been used in pharmacology modeling studies to show that at least six to seven doses per week are necessary to protect cervicovaginal tissue from HIV in women, whereas only two to three doses per week in men are required to protect colorectal tissue. ⁵ Hence, intermittent dosing of PrEP is not advised in women under any circumstances, especially as daily dosing has shown to foster better adherence, better coverage of potential sexual exposure, and more sustained use of PrEP. ⁷ It should be pointed out that there have been concerns about PrEP use promoting increased risky sexual behavior; however, the current medical literature has not supported this concern. ⁸ Adherence to PrEP is key to its efficacy, particularly for women. ^6,7 Accordingly, there are several ongoing studies evaluating PrEP compliance in women, different dosing strategies and delivery systems in women, and possibly combining the HIV prevention benefit of PrEP with another benefit such as contraception to offer additional motivation for adherence. ⁹

In 2014, the CDC issued guidelines on how to administer and monitor patients on HIV PrEP. ³ Those guidelines defined an at-risk woman as an individual with either an HIV-positive sexual partner, a recent bacterial STI, a high number of sexual partners, history of inconsistent or no condom use, or a woman who engages in commercial sex work. Once risk is assessed, the clinician should determine clinical eligibility by performing a history, physical and laboratory studies to rule out acute or chronic HIV infection, renal insufficiency, and evaluate for either hepatitis B infection or hepatitis B immunity status. If a person had a high-risk exposure within the past 15 days, or if there is concern for acute HIV infection, the clinician should consider performing both a HIV viral load (HIV RNA quantitation) test to rule out acute HIV and the HIV antibody test, because in the setting of active HIV infection, PrEP can result in the development of HIV resistance to tenofovir and emtricitabine. ³

Once the decision has been made to initiate PrEP, close monitoring is advised. PrEP is contraindicated in patients with creatinine clearance of less than 60 mL/min ³ . Follow-up visits should be scheduled at minimum every 3 months to provide medication adherence counseling and perform HIV testing, renal function assessment, STI symptom screening, and pregnancy testing. ³ At each visit, pregnancy intent should be assessed, and if pregnancy is not desired, the patient should be on an appropriate form of contraception. ³ To ensure patient follow-up every 3 months, it is generally advised that patients should be provided with no more than 90 days of medication at a time. Although typically well tolerated in practice, some patients may experience a “gastrointestinal start-up syndrome” when initiating PrEP, with development of constipation or diarrhea, nausea, anorexia, and/or weight loss. ¹⁰ This adverse reaction is self limited, usually lasting about 2–4 weeks. There are some noteworthy long-term side effects of PrEP, including renal dysfunction and bone mineral density loss. The bone mineral loss is typically 1% per 12 months; however, it is reversible once PrEP is discontinued. ³ Currently the CDC does not advise bone density assessment before PrEP initiation, or as part of monitoring while on PrEP. ³ Although assessment of creatinine clearance is usually adequate, further testing for proteinuria should be considered if a person has comorbid conditions that may also negatively affect renal function, such as hypertension or diabetes. ³

Hepatitis B status should be evaluated before PrEP initiation, as Truvada is also active against hepatitis B virus (HBV). If a person has chronic HBV infection and abruptly discontinues his or her PrEP, a HBV flare can occur and manifest as fulminant hepatitis or hepatic failure. ³ Those found to have chronic HBV during baseline testing should be referred to a specialist before HIV PrEP is initiated, as well as counseled that HBV can be transmitted to others via sexual contact. Persons without evidence of immunity against HBV should receive the complete HBV vaccination series, although they can be started on PrEP while receiving the vaccine series. ³

Without medical insurance, the cost of PrEP is ∼$1300 per month. ¹¹ Some state Medicaid plans do cover the prescription drug cost, and there are resources online to assist providers and patients with navigating the costs of the medication, laboratory testing, and surveillance visits. ¹¹ Patients can also be directed to the Gilead Sciences PrEP medication patient assistance program, which can help offset the prescription cost. ^11,12

Answer: The correct answer is B.

Our patient is at increased risk for HIV as she is in a serodiscordant relationship with an HIV-positive man whose HIV viral load is not fully suppressed. She should be counseled regarding the risks and benefits of HIV PrEP. If she chooses to proceed, she should have the appropriate screening laboratories performed, and if no contraindications are noted, she can be started on PrEP with strict adherence counseling. She should receive the hepatitis B vaccine if she is not already immune. She may continue lisinopril, assuming a normal creatinine clearance.