pre-exposure prophylaxis pre-exposure prophylaxis pre-exposure prophylaxis (prep) is the use of medications to prevent the spread of disease in people who have not yet been exposed to a disease-causing agent, usually a virus. the term typically refers to the use of antiviral drugs as a strategy for the prevention of hiv/aids. prep is one of a number of hiv prevention strategies for people who are hiv negative but who have a higher risk of acquiring hiv, including sexually active adults at increased risk of contracting hiv, people who engage in intravenous drug use (see drug injection), and serodiscordant sexually active couples. tablets of truvada, a tenofovir/emtricitabine combination used for hiv pre-exposure prophylaxis when used as directed, prep has been shown to be highly effective, reducing the risk of acquiring hiv by up to 99%. as of 2019, the world health organization (who) recommends two drug combinations for the use as prep for hiv/aids: the combination of tenofovir disoproxil and emtricitabine (truvada), or the combination of tenofovir disoproxil and lamivudine (cimduo). in october 2019, the us food and drug administration (fda) approved the combination of emtricitabine and tenofovir alafenamide (descovy) to be used as prep in addition to truvada, which provides similar levels of protection. in december 2021, the fda approved cabotegravir (apretude), which is an injectable form of prep manufactured by viiv, a pharmaceutical company that specializes in hiv drugs. regulators believe it will improve medication adherence because it only has to be taken once every two months, and will also widen adoption as it eliminates the need to hide pills or pharmacy visits for discretion. medical uses in the united states, federal guidelines recommend the use of pre-exposure prophylaxis (prep) for hiv-negative adults with the following characteristics: sexually active in the last six months and not in a sexually monogamous relationship with a recently tested hiv-negative partner, and who: is a man who has sex with men (msm), and who; has had anal sex with another man in the past six months without a condom, or; has had a sexually transmitted infection in the past six months; or is a sexually active adult (male or female with male or female partners), and who; is a man who has sex with both men and women, or; has sex with partners at increased risk of having hiv (e.g. intravenous drug users, men who have sex with men) without consistent condom use; or anyone who has injected illicit drugs in the past six months, shared recreational drug injection equipment with other drug users in the past six months, or has been in treatment for intravenous drug use in the past six months in the united kingdom the bhiva/bashh guidelines on the use of hiv pre-exposure prophylaxis (prep) 2018 recommend: on-demand or daily oral tenofovir – emtricitabine (td-ftc) for hiv-negative msm who are at elevated risk of hiv acquisition through unprotected anal sex in the previous six months and ongoing unprotected anal sex. on-demand or daily oral td-ftc for hiv-negative msm having unprotected anal sex with partners who are hiv positive, unless the partner has been on art for at least six months and their plasma viral load is <200 copies/ml. tenofovir (tdf) alone should not be offered to msm. daily oral td-ftc for hiv-negative heterosexual men and women having unprotected sex with partners who are hiv positive, unless the partner has been on art for at least six months and their plasma viral load is <200 copies/ml. daily oral td-ftc for heterosexual men and women on a case-by-case basis with current factors that may put them at increased risk of hiv acquisition. tdf alone can be offered to heterosexual men and women where ftc is contraindicated. prep is not recommended for people who inject drugs where needle exchange and opiate substitution programs are available and accessed by the individual. prep with daily oral td-ftc for hiv-negative trans women who are at risk of hiv acquisition through unprotected anal sex in the previous six months and ongoing unprotected sex. daily oral td-ftc for hiv-negative trans women and trans men who have unprotected sex with partners who are hiv positive, unless the partner has been on art for at least six months and their plasma viral load is <200 copies/ml. other government health agencies from around the world have devised their own national guidelines for how to use prep to prevent hiv infection in those at high risk, including botswana, canada, kenya, lesotho, south africa, uganda, the zambia, and zimbabwe. often, laboratory testing is required before starting prep, including a test for hiv. once prep is initiated, individuals are asked to see their healthcare provider at least every three to six months. during those visits, providers may want to repeat testing for hiv, test for other sexually transmitted infections, monitor kidney function, and/or test for pregnancy. individuals must test negative for hiv prior to prep initiation because persons infected with hiv taking prep medication are at risk for becoming resistant to emtricitabine. consequently, people with hiv infection and resistance to emtricitabine will have fewer options for selecting hiv treatment medications. prep has been shown to be effective at reducing the risk of acquiring hiv in individuals at increased risk. however, prep is not 100% effective at preventing hiv, even in people who take the medication as prescribed. there have been several reported cases of people who acquired hiv despite taking prep. people taking prep may use combination prevention strategies along with prep, like condoms. if someone on prep acquires hiv, they may experience the signs and symptoms of hiv/aids. a bottle of a generic version of emtricitabine/tenofovir, used for prep prep is typically taken continuously and daily following potential exposure. the cdc recommends follow-up visits at least every three months to provide hiv tests, medication adherence counseling, behavioral risk reduction support, side effect assessment, sti symptom assessment, and sti testing for sexually active individuals with symptoms of a current infection. pregnancy tests should also be done every three months for woman who may become pregnant. at three months and every six months thereafter, renal function and presence of bacterial sti is assessed. effectiveness of prep is associated with adherence, with effectiveness decreasing with suboptimal adherence. although the daily, oral dosing schedule is still recommended for all individuals taking prep medication for hiv infection prevention, event-driven pre-exposure prophylaxis, or ed-prep, is an option for men who have sex with men. ed-prep is also referred to as "2+1+1" dosing, because the dosing regimen involves a person taking two pills two to twenty-four hours prior to sex, one pill twenty-four hours after taking the first two pills, and a last pill taken forty-eight hours after taking the first two pills. this dosing regimen was first proven effective to reduce the relative risk of hiv infection by 86% in the ipergay randomized clinical trial performed in canada and france in 2015. this has only been evaluated with truvada and not other drugs. according to the who, ed-prep should be considered for hiv infection prevention in men who have sex with men who have relatively infrequent sex, who are able to plan sex or delay sex for about two hours, and who find this dosing schedule convenient. ed-prep is not recommended for use in other populations, such as cisgender or transgender women and men who have vaginal and/or anal sex with women, due to the lack of safety and efficacy data available studying ed-prep in these populations. ed-prep can be beneficial to help reduce the pill burden for people and decrease costs, as fewer pills are needed. in 2016, the world health organization (who) consolidated guidelines regarding the use of antiretroviral drugs for treatment and prevention of hiv infection support the use of prep in pregnant and breastfeeding women who are at continued and substantial risk of hiv infection. in clinical prep trials, exposure to tdf-containing prep during the first trimester of pregnancy was not associated with adverse pregnancy or infant outcomes. the increased risk of mother-to-child hiv transmission outweighs any potential risks of prep. the guidelines also note the need for continued monitoring of pregnant and breastfeeding women receiving prep. however, global prep accessibility for women, including those who are either pregnant or breastfeeding, is limited. efforts to increase accessibility to women who are at risk for hiv are necessary for reducing rates of global hiv infections. contraindications truvada and descovy truvada and descovy are contraindicated for use as pre-exposure prophylaxis (prep) in individuals who have an unknown or positive hiv status. hiv positive or negative status must be determined before someone begins the use of either of these medications as prep. additionally, any hypersensitivity or severe allergy to any ingredient, emtricitabine, tenofovir disoproxil, or tenofovir alafenamide is a contraindication for continued use of these medications. side effects research shows that pre-exposure prophylaxis (prep) is generally safe and well tolerated for most individuals, although some side effects have been noted to occur. some people experience a "start-up syndrome" involving nausea, headache, and/or stomach issues, which generally resolve within a few weeks of starting the prep medication. research has shown that the use of truvada as prep has been associated with mild to moderate declines in kidney function, mostly associated with older people over 50, those with predisposing conditions such as diabetes, or glomerular filtration rate lower than 90. these declines were usually of no concern, stabilized after several weeks of being on the drug, and reversed once the drug was discontinued. however, these side effects were serious enough for several people on prep to file lawsuits against the makers of truvada as well as the makers of other similar drugs. osteopenia or bone loss has been reported in clinical studies. bone loss was not seen as a major concern for ending the service since bone loss was considered minimal and did not lead to osteoporosis. when comparing bone fractures between active participants and control there was no major difference in bone fractures. fat redistribution and accumulation was more commonly seen in individuals receiving antiretroviral therapy, particularly older antiretrovirals, for the treatment of hiv. no significant changes in fat redistribution or change in fat had been noted as of february 2018 when used as a pre-exposure prophylaxis. research and study outcome analysis suggests that emtricitabine/tenofovir does not have a significant effect on fat redistribution or accumulation when used as pre-exposure prophylaxis in hiv negative individuals. as of early 2018 these studies have not assessed in detail subtle changes in fat distribution that may be possible with the drug when used as prep, and statistically significant – though transient – weight changes have been attributed to detectable drug concentrations in the body. other potential serious side effects of truvada include acute exacerbations of hepatitis b in individuals with hbv infection, lactic acidosis, and severe hepatomegaly with steatosis. descovy research and data from public use has shown similar "start-up" effects; however, some data indicates that descovy is better for one's kidneys and for those with a diagnosis of osteoporosis. the discover trial that compared descovy versus truvada for prep showed that descovy produced safer kidney and bone outcomes. boxed warnings both truvada and descovy carry a black box warning for the combination of emtricitabine/tenofovir, as this combination of drugs can result in the acute worsening of hepatitis b infection when discontinued. this combination of drugs is also known to increase hiv resistance to these medications when used as pre-exposure prophylaxis (prep) in individuals who have already (recently) been infected with hiv. it is recommended that individuals continue to periodically get tested to determine their hiv status to ensure proper continuing use of these medications for prep. society and culture access and adoption approved approved for off-label use ongoing and planned demonstration projects completed demonstration projects no planned demonstration project no data approval for use truvada was previously only approved by the u.s. food and drug administration (fda) to treat hiv in those already infected. in 2012, the fda approved the drug for use as pre-exposure prophylaxis (prep), based on growing evidence that the drug was safe and effective at preventing hiv in populations at increased risk of infection. the fda has approved two additional medications for prep since then, approving descovy in 2019 and cabotegravir (apretude) in 2021. in 2012, the world health organization (who) issued guidelines for prep