Pre-exposure prophylaxis


Pre-exposure prophylaxis is a term used to describe the use of medications used 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 specific use of antiviral drugs as a strategy for HIV/AIDS prevention.
PrEP is one of a number of HIV prevention strategies for people who are HIV negative but who also have higher risk of acquiring HIV, including sexually active adults at increased risk of HIV, people who engage in injection drug use, and serodiscordant sexually active couples. Other strategies can include the use of condoms, as well as harm reduction methods of using clean resources provided by safe injection sites and needle exchange programs.
, the World Health Organization recommends two drug combinations for the use as PrEP for HIV/AIDS: the combination of tenofovir disoproxil and emtricitabine, for example, in the form of Truvada, which is the brand name of the Gilead Sciences, or the tenofovir/lamivudine combination. In October 2019, the U.S. Food and Drug Administration approved Descovy to be used as PrEP in addition to Truvada, which provides similar levels of protection.
When used as directed, PrEP has been shown to be highly effective, reducing the risk of acquiring HIV up to 99%.

Clinical use

In the United States, federal guidelines recommend the use of PrEP for HIV-negative adults with the following characteristics:
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 United Kingdom, Zambia, and Zimbabwe.
Often, lab testing is required before starting PrEP, including a test for HIV. Once PrEP is initiated, patients are asked to see their provider at least every three to six months. During those visits, healthcare providers may want to repeat testing for HIV, test for other sexually transmitted infections, monitor kidney function, and/or test for pregnancy. Patients must test negative for HIV prior to PrEP initiation, because patients infected with HIV taking PrEP medication are at risk for becoming resistant to emtricitabine. Consequently, these patients with HIV infection and resistance to emtricitabine will have less 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.
PrEP is typically taken continuously and daily following potential exposure. The CDC currently recommends follow-up visits at least every 3 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 current infection. Pregnancy tests should also be done every 3 months for woman who may become pregnant. At 3 months and every 6 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 patients 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 patient 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. 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 pill burden for patients and decrease costs, as fewer pills are needed.
The 2016 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 outweigh 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 in reducing rates of global HIV infections.

Side effects

Research has shown that PrEP is generally safe and well tolerated for most patients, although some side effects have been noted to occur. Some patients 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 their was no major difference in bone fractures.
Fat redistribution and accumulation has been observed in patients receiving antiretroviral therapy, particularly older antiretrovirals, including fat reductions in the face, limbs, and buttocks and increases in visceral fat of the abdomen and accumulations in the upper back. 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. Anecdotal evidence does not currently suggest significant reductions in facial or gluteal region adipose tissue and among PrEP users; the drug does not have a "reputation" as a cause of fat changes.
Other potential side effects of Truvada include acute exacerbations of hepatitis B in patients with HBV infection, bone loss, lactic acidosis, and severe hepatomegaly with steatosis.

Access and adoption

Approval for use

Truvada was previously only approved by the U.S. Food and Drug Administration to treat HIV in those already infected. In 2012, the FDA approved the drug for use as PrEP, based on growing evidence that the drug was safe and effective at preventing HIV in populations at increased risk of infection.
In 2012, the World Health Organization issued guidelines for PrEP and made similar recommendations for its use among men and transgender women who have sex with men. The WHO noted that "international scientific consensus is emerging
that antiretroviral drugs, including PrEP, significantly reduce the risk of sexual acquisition and transmission of HIV regardless of population or setting." In 2014, on the basis of further evidence, the WHO updated the recommendation for men who have sex with men to state that PrEP "is recommended as an additional HIV prevention choice within a comprehensive HIV prevention package." In November 2015 the WHO expanded this further, on the basis of further evidence, and stated that it had "broadened the recommendation to include all population groups at substantial risk of HIV infection" and emphasized that PrEP should be "an additional prevention choice in a comprehensive package of services."
, numerous countries have approved the use of PrEP for HIV/AIDS prevention, including the United States, South Korea, France, Norway, Australia, Israel, Canada, Kenya, South Africa, Peru, Thailand, the European Union and Taiwan.
New Zealand was one of the first countries in the world to publicly fund PrEP for the prevention of HIV in March 2018. Funded access to PrEP will require that people undergo regular testing for HIV and other sexually transmitted infections, and are monitored for risk of side effects. People taking funded PrEP will receive advice on ways to reduce the risk of HIV and sexually transmitted infections.
In Australia, the country's Therapeutic Goods Administration approved the use of Truvada as PrEP in May 2016, allowing Australian providers to legally prescribe the medication. On March 21, 2018, the Federal Minister for Health announced that PrEP will be subsidized by the Australian Government through the Pharmaceutical Benefits Scheme from April 1, 2018.

Availability and pricing in the United States

In December 2019, the U.S. announced the Ready, Set, PrEP program to provide free PrEP to the uninsured through major drugstore chains.
NPIN PrEP Provider Data and Locator Widget was launched on the CDC website to provide a comprehensive, national directory of public and private providers in the U.S. that offer pre-exposure prophylaxis to prevent HIV infection. The database includes over 1,800 PrEP providers from all 50 U.S. states, as well as U.S. territories.
Beginning in January 2020, after California Governor Gavin Newsom signed Senate Bill 159 in late 2019, licensed CA pharmacists are now authorized to initiate and dispense PrEP/PEP medications without a doctor's prescription, given certain clinical criteria of the patient are met. The bill acts as an extension of Medi-Cal benefits. This bill is recognized by pharmacist organizations, health providers, legislators, and the general public to be the removal of a barrier to direct and time-dependent access to these medications, especially for those in communities most affected by HIV/AIDs.

Politics and Culture

Since the FDA approval of PrEP for the prevention of HIV, moves toward greater adoption of PrEP have been met some issues, especially around the overall public health effect of widespread adoption, the cost of PrEP and associated disparities in availability and access. Many public health organizations and governments have embraced PrEP as a part of their overall strategy for reducing HIV. For example, in 2014 New York state governor Andrew Cuomo initiated a three-part plan to reduce HIV across New York that specifically emphasized access to PrEP. Similarly, the city of San Francisco launched a "Getting to Zero" campaign. The campaign aims to dramatically reduce the number of new HIV infections in the city and relies on expanding access to PrEP as a key strategy for achieving that goal. Public health officials report that since 2013 the number of new HIV infections in San Francisco has decreased almost 50% and that such improvements are likely related to the city's campaign to reduce new infections. Additionally, numerous public health campaigns have been launched to educate the public about PrEP. For instance, in New York City in 2016 Gay Men's Health Crisis launched an ad campaign in bus shelters across the city reminding riders that adherence to PrEP is important to ensuring the regimen is maximally effective. In Washington, D.C., a PrEP campaign was launched to increase the number of D.C. residents taking PrEP. Social media pushes, such as an ad campaign called “PrEP for Her”, targeted African-American women, who, along with gay and bisexual African-American men, are at high risk of infection in the district.
Despite those efforts, PrEP remains controversial among some who worry that widespread PrEP adoption could cause public health issues by enabling risky sexual behaviors. For instance, AIDS Healthcare Foundation founder and director Michael Weinstein has been vocal in his opposition to PrEP adoption, suggesting that PrEP causes people to make riskier decisions about sex than they would otherwise make. Some researchers, however, believe that there is insufficient data to determine whether or not PrEP implementation has an effect on the rate of other sexually transmitted infections. Other critics point out that despite implementation of PrEP, significant disparities exist. For example, some point out that African Americans bear a disproportionate burden of HIV infections but may be less likely than whites to access PrEP. Still other critics of PrEP object to the high cost of the regimen. For example, the U.K.'s NHS initially refused to offer PrEP to patients citing concerns about cost and suggested that local officials ought to bear the responsibility of paying for the drug. However, following significant advocacy efforts, the NHS has started to offer PrEP to patients in the UK in 2017.

Changes in gay sex culture

Currently PrEP is used predominantly by gay men, often as an alternative to condoms. For the first time since the outbreak of the AIDS crisis, PrEP makes HIV-protected sex without condoms possible and has therefore changed gay sex culture: With the spread of PrEP, condomless sex has increased. But because the condom was for a long time the only effective HIV prevention tool, many gay men do not feel comfortable with condomless sex. Apart from criticisms of PrEP stemming from potential side effects or from concerns that it may raise the risk of spreading sexually transmitted diseases other than HIV, the rejection of PrEP is sometimes connected to a stigma against the acceptability of promiscuous sexuality - a stigma which is present in both online dating platforms such as Grindr, but also to some extent in the media - since PrEP has been perceived to promote promiscuity. PrEP can itself contribute to reducing stigma and homophobia, however, because it can help to dissolve the association between gay sex and risk of disease that has been socially prevalent since the outbreak of the AIDS crisis.

Research

Most PrEP studies use the drug tenofovir or a tenofovir/emtricitabine combination that is delivered orally. Initial studies of PrEP strategies in non-human primates showed a reduced risk of infection among animals that receive ARVs prior to exposure to a simian form of HIV. A 2007 study at UT-Southwestern and the University of Minnesota showed PrEP to be effective in "humanized" laboratory mice. In 2008, the iPrEx study demonstrated 42% reduction of HIV infection among men who have sex with men, and subsequent analysis of the data has suggested that 99% protection is achievable if the drugs are taken every day. Below is a table summarizing some of the major research studies that demonstrated PrEP with Truvada to be effective across different populations.
PrEP approaches with agents besides oral Truvada are being investigated. There has been some evidence that other regimens, like ones based on the antiretroviral agent Maraviroc, could potentially prevent HIV infection. Similarly, researchers are investigating whether drugs could be used in ways other than a daily oral pill to prevent HIV, including taking a long-acting PrEP injection, PrEP-releasing implants, or rectally administered PrEP. However, it is important to keep in mind that as of 2017 major public health organizations such as the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend only daily oral Truvada for use as PrEP.
Current data on efficacy and safety of PrEP in adolescents are insufficient. Risks and benefits of PrEP use should be considered for adolescents.
StudyTypeType of PrEPStudy PopulationEfficacyPercent of patients who took medication
CAPRISA 004Double-blind, randomizedPericoital tenofovir gelSouth African females39% reduction of HIV infection72% by applicator count
iPrExOral emtricitabine/tenofovirMen who have sex with men and transgender women42% reduction of HIV infection. 99% reduction estimated with daily adherence54% detectable in blood
Partners PrEPOral emtricitabine/tenofovir; oral tenofovirAfrican heterosexual couplesReduction of infection by 73% with Truvada and 62% with tenofovir80% with Truvada and 83% with tenofovir detectable in blood
TDF2Oral emtricitabine/tenofovirBotswana heterosexual couples63% reduction of infection84% by pill count
FEM-PrEPOral emtricitabine/tenofovirAfrican heterosexual femalesNo reduction <30% with detectable levels in blood
VOICE 003Oral emtricitabine/tenofovir; oral tenofovir; vaginal tenofovir gelAfrican heterosexual femalesNo reduction in oral tenofovir or vaginal gel arms <30% with detectable levels in blood
Bangkok Tenofovir StudyRandomized, double-blindOral tenofovirThai male injection drug users48.9% reduction of infection84% by directly observed therapy and study diaries
IPERGAYRandomized, double-blindOral emtricitabine/tenofovirFrench and Quebecois gay males86% reduction of infection 86% with detectable levels in blood
PROUDRandomized, open-labelOral tenofovir-emtricitabineHigh-risk men who have sex with men in England86% reduction of HIV incidence-
HPTN 083Randomized, double-blindCabotegravir versus emtricitabine/tenofovirTransgender women and cisgender men who have sex with men in Argentina, Brazil, Peru, Thailand, the U.S., Vietnam, and South Africa.Highly efficacious compared to daily oral TDF/FTC.-
Discover studyRandomized, double-blindoral TDF/FTC versus TAF/FTCHigh-risk men who have sex with men in Europe, North and South Americaongoing-

Possibility of increased risk-taking

While PrEP appears to be extremely successful in reducing HIV infection, there is mixed evidence that there might be a change in use of condoms in anal sex, raising risks of spreading sexually transmitted diseases other than HIV. In a meta-analysis of 18 studies, researchers found that rates of new diagnoses of STIs among MSM given PrEP were 25.3 times greater for gonorrhea, 11.2 times greater for chlamydia and 44.6 times greater for syphilis, compared with the rates among MSM not given PrEP. Unlike HIV, these three STIs can be cured with antibiotics. However, the increased rates of such infections and their treatment can lead to antibiotic-resistant mutations of the pathogens; antibiotic-resistant gonorrhea is already a major concern.
A systemic review conducted in 2019 was unable to find conclusive evidence that PrEP use increases sexual risk behaviors, and found that PrEP may provide an opportunity for MSM to access sexual health care, testing, treatment and counselling services.