The "Five Ps" approach elicits sexual history information related to five key areas of interest: partners, practices, prevention of pregnancy, protection against STIs, and past history [1].

All sexually active adolescents are considered at increased risk for STIs and should be counseled. Other at-risk groups include adults with current or past-year STIs, with multiple sex partners, or who use condoms inconsistently. African Americans have the highest STI prevalence of any racial/ethnic group, and STI prevalence is higher in American Indians, Alaska Natives, and Latino/as than in white populations. Increased STI prevalence rates are also found in men who have sex with men (MSM), persons with low incomes living in urban settings, current or former inmates, military recruits, persons who exchange sex for money or drugs, persons with mental illness or a disability, current or former injecting drug users (IDUs), persons with sexual abuse history, and patients of public STI clinics [3].

As U.S. Food and Drug Administration (FDA)-regulated medical devices, condoms are subject to quality-control testing. Each latex condom manufactured in the United States is tested electronically for holes before packaging. The rate of condom breakage during sexual intercourse and withdrawal is approximately 2 per 100 condoms used, with slightly higher rates during anal intercourse [7,8]. Condom failure to protect against STI or unintended pregnancy is usually caused by inconsistent or incorrect use, instead of condom breakage [9]. Latex condoms should not be used beyond their expiration date or more than five years after the manufacturing date, and users should check the expiration or manufacture date on the packaging before use [1]. In 2022, the FDA cleared the first natural rubber latex condom designed specifically to be used in anal intercourse [150].

External condoms made of materials other than latex fall in two general categories: synthetic and natural membrane condoms. Polyurethane and other synthetic condoms provide protection against STIs/HIV and pregnancy comparable to latex condoms and are used mainly as latex condom substitutes by persons with latex allergy. These condoms are more resistant to deterioration and are compatible with oil-based or water-based lubricants. The preventive efficacy of other synthetic external condoms is not well studied, and the FDA restricts their use to persons with latex sensitivity or allergy [6,10].

Natural membrane condoms (termed "natural skin" or "lambskin") are made from lamb cecum. The pores, no greater than 1,500 nm in diameter, block passage of sperm but are more than 10 times the diameter of HIV and more than 25 times that of HBV. Therefore, sexual transmission of hepatitis B, herpes simplex, and HIV organisms can occur with natural membrane condoms. These condoms are recommended for preventing pregnancy but not STIs/HIV [10,11,12].

Penile circumcision has been found to reduce the risk for HIV and some STIs in heterosexual men. By various means, penile foreskin is the primary biologic weak point and conduit for HIV infection during heterosexual intercourse [15]. Several controlled studies of heterosexual HIV transmission in sub-Saharan Africa found circumcision reduced the risk for HIV acquisition in men by 50% to 60% and protected against high-risk genital HPV infection and genital herpes [16,17,18]. These benefits of circumcision were sustained over time, and the effects were not solely related to reductions in herpes simplex virus type 2 (HSV-2) infection or genital ulcer disease [19,20].

In the United States, approximately one in eight persons 14 to 49 years of age is infected with HSV-2. Human infection persists throughout life, and prevalence rates in the population increase by age group due to cumulative sexual exposures [37]. Most people infected with genital herpes go undiagnosed. While many of those who harbor HSV-2 have minimal or no signs and symptoms, viral shedding recurs intermittently from anogenital sites [38]. As a result, most genital herpes infections are transmitted by individuals who are unaware of their infection or asymptomatic when infectious. Risk of transmission is highest when a new crop of vesicles erupts in the anogenital area [3,36].

HSV serologic testing is used for persons presenting for general STI evaluation (especially with multiple sex partners), those with HIV infection, and MSM at increased risk for HIV. Serologic HSV antibody testing detects the specific immune protein response to herpes infection. Several days after the primary (initial) HSV infection, immunoglobulin M (IgM) antibody is produced, remaining detectable in serum for several weeks. Soon after the appearance of HSV IgM, the body begins producing anti-HSV IgG antibody. IgG serum levels rise for several weeks, then slowly decline, stabilize, and remain detectable throughout life [42,45]. With type-common antibody testing, positive HSV IgM antibody indicates active or recent infection, while positive HSV IgG antibody indicates previous infection. A significant recent increase in HSV IgG antibodies is a sign of reactivation or recent primary infection. Negative HSV antibody testing implies HSV exposure is unlikely or the body has had insufficient time to produce HSV antibodies [42,45].

Genital HPV is the most common sexually transmitted infection in the United States. Most HPV infections are asymptomatic or unrecognized and clear or become undetectable within one to two years. During 2013–2016, the estimated prevalence of genital HPV in the United States adult population 18 to 59 years of age was 40.0% overall—41.8% in men and 38.4% in women [75]. The prevalence of disease-associated HPV infection was 24.2% in men and 19.9% in women. The CDC estimates that, in 2021, 13 million persons had an incident infection with a disease-associated HPV [1]. Around 200 phylogenetically related HPV genotypes have been identified, including approximately 40 types that infect the anogenital mucosal epithelium.

Prevention of high-risk HPV and the associated disease burden caused by HPV can be achieved through prophylactic vaccination. HPV vaccines target the genotypes responsible for most HPV-attributable cancers and are highly effective for prevention of vaccine-type precancers [161]. The FDA has approved three vaccines for protection against HPV diseases and attributable cancers. A bivalent vaccine (Cervarix) and Gardasil were previously available but are no longer used in the United States. The currently recommended vaccine is nine-valent Gardasil 9, which protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 [80,81]. The types prevented by nine-valent vaccination account for approximately 90% of HPV-attributable cancers worldwide [161].

All boys and girls 11 to 12 years of age are now recommended to receive HPV vaccines, as they are most effective when given at younger ages, before the onset of sexual activity and initial exposure to the virus. The earliest approved age is 9 years. The vaccine in clinical use is recommended for girls/women and boys/men. Young sexually active individuals should still receive the vaccination, because those already infected with one type of HPV may benefit from the protection against other types included in the vaccine. In those who have not received any or all vaccine doses, vaccination is recommended through 26 years of age for all girls/women and boys/men [80]. HPV vaccine is also recommended for those 27 to 45 years of age if desired or if a risk factor is present.

Genital warts (condyloma acuminatum) are benign and mainly caused by HPV types 6 and 11. The types affecting the anogenital region are usually transmitted sexually by penetrative vaginal or anal intercourse, but digital, oral, and nonpenetrative genital contact may be involved. The development of genital warts is more common in patients who are immunocompromised. Growth rates vary, but pregnancy, immunosuppression, or maceration of the skin may accelerate the growth and spread of warts [89].

Hepatitis is an inflammatory state of the liver. Most cases of hepatitis are caused by viral infection; other causes include exposure to chemicals, over-the-counter or prescription drugs, heavy alcohol use, inherited diseases, autoimmune disease, and fatty buildup in the liver [104]. In all patients with symptoms that suggest acute viral hepatitis, clinicians should assess the patient and, if necessary, refer for hospital admission. Tests should be performed to assess hepatitis severity, including liver function tests, coagulation tests, and hepatitis serology (i.e., anti-HAV IgM, HBsAg, hepatitis C virus [HCV] antibodies/RNA, and hepatitis E serology/PCR) [105].

The icteric phase is characterized by jaundice (mixed hepatic and cholestatic) and is associated with anorexia, nausea, and fatigue that usually lasts one to three weeks. This phase can persist 12 or more weeks in a minority of patients who have cholestatic symptoms (e.g., itching, deep jaundice). Fever is rare. Up to 10% of patients experience symptomatic relapse in the six months following acute illness.

After an incubation period of 40 to 160 days, high levels of HBV appear in the blood, followed by low levels of virus in wound exudates, semen, vaginal secretions, and saliva. HBV is efficiently transmitted by percutaneous or mucous membrane exposure to infected blood or body fluids. HBV is more infectious and more stable in the environment than other bloodborne pathogens, including HCV and HIV [1].

HBV vaccination is recommended for the following unvaccinated persons [120]:

In 2021, an estimated 38.4 million people globally were living with HIV, 1.5 million had become newly infected that year, and 650,00 people died of AIDS-related illnesses [82]. About 75% of people with HIV (28.7 million) were receiving antiretroviral therapy. Women and girls accounted for about 49% of all new infections. Since 2010, new infections have declined overall by 32% and among children have declined by 52%. AIDS-related deaths have been reduced by 68% since the peak in 2004 [82]. In 2021, 36,136 people were newly diagnosed with HIV in the United States and dependent areas. Male-to-male sexual contact accounted for 67% of all new diagnoses, heterosexual contact for 22% [129]. The incidence of new cases decreased 7% from 2017 to 2021. According to the CDC, an estimated 1.2 million people in the United States had HIV at the end of 2021; of these people, an estimated 13% were unaware they had HIV [129].

The highest risk of HIV infection comes from unprotected receptive anal intercourse, followed by unprotected receptive vaginal intercourse and unprotected insertive anal intercourse (particularly for uncircumcised men) [134,135]. Risk of transmission is reduced using latex condoms. For the wearer, latex condoms provide a mechanical barrier limiting penile exposure to infectious cervical, vaginal, vulvar, or rectal secretions or lesions. Likewise, the partner is protected from infectious pre-ejaculate, semen, and penile lesions. As discussed, natural membrane condoms (made from lamb cecum) contain small pores and do not block HIV passage. It is estimated that latex condom use reduces the risk of HIV transmission by approximately 70% to 80% [136,137,138]. Although abstinence from sexual contact is the sole way to absolutely prevent sexual transmission, sexual activity in a mutually monogamous relationship in which neither partner is HIV-infected and no other risk factors are present is considered safe [139]. However, men who identify publicly as heterosexual and generally have committed relationships with women, but who also engage in sexual activity with other men, may be a transmission bridge to heterosexual women [140]. To better understand the actual extent of this behavior and its impact on HIV transmission, more research is necessary.

In 2021, the CDC and the U.S. Department of Health and Human Services updated its clinical practice guidelines for pre-exposure prophylaxis/prevention of HIV infection [145]. This guideline outlines indications for prophylaxis as one option for preventing HIV transmission. The most important first step in determining if an individual is a candidate for pre-exposure prophylaxis is a thorough history, including sexual and injection drug activities. All candidates will be adults without an acute or established HIV diagnosis. Pre-exposure prophylaxis is indicated for high-risk MSM, meaning those who have had any male sex partners in the past six months, are not in a monogamous partnership with a recently tested, HIV-negative man, and have one of the following [145]: