#94182: Viral Sexually Transmitted Infections

Practical strategies for risk assessment and counseling are provided in the CDC treatment guidelines document [1]. Health providers should use simple, direct language when asking these questions, taking care to exhibit respect, compassion, and a nonjudgmental attitude. Organizations such as the National Network of STI/HIV Prevention Training Centers, a CDC-funded group, can help providers enhance skills in counseling individuals about prevention. Resources can be found online at https://www.cdc.gov/std/treatment/resources.htm.

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].

Behavioral counseling interventions can reduce the risk of acquiring an STI. Interventions ranging in intensity from 30 minutes to more than 2 hours of contact time are beneficial; evidence of benefit increases with intervention intensity [3]. Interventions can be delivered by primary care clinicians or through referral to trained behavioral counselors. Successful interventions provide basic information on STIs and STI transmission; assess patient risk for transmission; and provide pertinent skills training, such as condom use, communication about safe sex, problem solving, and goal setting. Many successful interventions aim to increase motivation or commitment to safe sex practices [3]. Specific counseling messages for patients diagnosed with genital herpes, HPV, or hepatitis are described in later sections of this course.

Nonspecific topical microbicides are ineffective in preventing HIV, and spermicides containing nonoxynol-9 (N-9) might disrupt genital or rectal epithelium to increase the risk for HIV infection [21,22]. In one study, condoms plus N-9 were no more effective than condoms alone for the prevention of STIs, and N-9 alone or in addition to a condom is not recommended for STI prevention [23]. N-9 use may also increase the risk for bacterial urinary tract infection in women [24]. As of 2020, no topical antiretroviral agent has been proven effective in preventing HIV, but vaginal and rectal microbicides using tenofovir and other antiretroviral drugs are under investigation [25].

Uncontrolled studies found that diaphragms protected against cervical gonorrhea, chlamydia, and trichomoniasis, but controlled studies found that compared with external condoms, diaphragms plus lubricant did not improve protection against HIV or herpes acquisition [26]. Diaphragms should not be solely relied on for protection against HIV/STIs [27,28].

Contraceptive methods that are not mechanical barriers provide no protection against HIV or other STIs. Sexually active women who use hormonal contraception, nonhormonal intrauterine devices, or have been surgically sterilized or undergone a hysterectomy should be advised to use condoms to reduce risks for STIs [10].

Vaginal washing and douching after sexual exposure are ineffective in protecting against HIV and STIs. These practices may increase the risk for bacterial vaginosis, some STIs, and HIV infection [1,29].

In patients seeking medical care for genital ulcers or other mucocutaneous lesions, cell culture and polymerase chain reaction (PCR) testing can detect herpes from a vesicle scraping [42]. If vesicles or pustules are present, these lesions should be unroofed, and the base of the ulcer swabbed to obtain adequate material for virus detection. Cell culture can distinguish HSV-1 from HSV-2, but it takes at least two days to complete. In addition, false negatives can occur with low viral load in the sample, and sensitivity is low, especially with recurrent or partially healed lesions [42]. PCR has sufficient sensitivity to detect HSV in low virus concentrations, and it is preferred for diagnosing systemic HSV infections, meningitis, central nervous system (CNS) involvement (encephalitis), and neonatal herpes [42,43,44].

The U.S. Preventive Services Task Force recommends against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including those who are pregnant.

(https://jamanetwork.com/journals/jama/fullarticle/2801311 Last Accessed: June 14, 2023)

Strength of Recommendation/Level of Evidence: D (There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.)

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].

HSV antibody tests can also diagnose herpes by detecting HSV-1 or HSV-2 (type-specific) viral type. The most accurate type-specific HSV serologic assays are glycoprotein G (gG)-based [42,46,47].

The presence of anti-HSV-1 IgG alone is nonspecific and of little diagnostic import because most adults are seropositive, having acquired oral HSV-1 infection during childhood. However, genital HSV-1 is increasing and can be asymptomatic, so typing alone is not a predictor of the likely infection site [38,48]. General population screening for HSV-1/2 is not indicated, but all patients with HSV-2 should be tested for HIV infection [3]. Selective serologic screening may be helpful in patients presenting without current symptoms of genital herpes, given that most individuals who have acquired genital HSV are not aware that they have the infection. CDC guidelines suggest that testing be considered in patients presenting for STI screening and/or those who have high-risk sexual behavior, as well as those with HIV infection and MSM at risk for HIV acquisition [1].

Newly acquired genital herpes can cause prolonged clinical illness, with severe genital ulcerations and neurologic involvement. Even patients with mild first-episode herpes symptoms can develop severe or prolonged symptoms, and all patients with an episode of genital herpes should receive antiviral therapy [51,52].

Almost all patients with symptomatic first-episode genital HSV-2 will subsequently experience recurrent episodes of genital lesions, and intermittent asymptomatic shedding occurs in genital HSV-2 patients, even with dormant infection [53]. Antiviral therapy for recurrent genital herpes can be administered continuously (daily) to suppress recurrence frequency or episodically to ameliorate or shorten active lesion duration [54]. Many patients prefer suppressive therapy, which also decreases the risk of genital HSV-2 transmission to susceptible partners [55].

Suppressive Therapy

In patients with frequent recurrence, suppressive therapy reduces recurrences by 70% to 80%, and many patients report an absence of symptomatic breakouts [50,52]. Continuous treatment also benefits patients with less frequent recurrences. Safety and efficacy are documented with daily acyclovir therapy taken as long as six years, and valacyclovir or famciclovir for one year [56,57]. Suppressive therapy also reduces genital shedding and the risk of transmission and leads to greater improvements in quality of life than episodic treatment [58].

Even in the absence of treatment, the frequency of genital herpes recurrences diminishes over time in many patients and may result in psychologic adjustment to the disease. During suppressive treatment, providers should discuss the need to continue therapy, but treatment discontinuation or laboratory monitoring in healthy patients is unnecessary [1].

Daily treatment with antiviral therapy can decrease HSV-2 transmission rates in infection-discordant heterosexual couples. Such couples should be encouraged to consider suppressive antiviral therapy to prevent transmission, to consistently use condoms, and to avoid sexual activity during recurrences. Suppressive antiviral therapy is also likely to reduce transmission by patients with multiple partners (including MSM) and in HSV-2 seropositive patients without a history of genital herpes [50,52,53].

Acyclovir, famciclovir, and valacyclovir have comparable efficacy as episodic genital herpes treatment, while famciclovir appears somewhat less effective in suppressing viral shedding [54,59]. Important considerations with prolonged treatment include costs and the ease of administration. Allergic and adverse reactions to oral acyclovir, valacyclovir, and famciclovir are rare. However, desensitization to acyclovir has been described [60].

Episodic Therapy

Effective episodic treatment of recurrent herpes requires initiation of therapy within one day of lesion onset or during the prodromal period before an outbreak. The patient should be provided with a supply of drug or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin [1].

Intravenous (IV) acyclovir therapy should be provided for patients with severe HSV disease or complications that require hospitalization, including disseminated infection, pneumonitis, hepatitis, or CNS complications (meningoencephalitis) [1].

Sex partners of patients with genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients with HSV-2. Asymptomatic sex partners should be assessed for a history of genital lesions and offered type-specific serologic HSV testing [1].

Episodic anogenital or oral herpes in immunocompromised patients can be severe and prolonged. HSV lesions are common in patients with HIV infection and may be severe, painful, and atypical. While antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes outbreaks, frequent subclinical viral shedding still occurs. Clinical manifestations of genital herpes may worsen during immune reconstitution following initiation of antiretroviral therapy [61,62].

Chronic suppressive or episodic oral antiviral therapy decreases the clinical manifestations of HSV in patients with HIV infection [63]. HSV type-specific serologic testing may be offered to persons with HIV infection during their initial evaluation if infection status is unknown, and suppressive antiviral therapy may be considered in those who have HSV-2 infection. In patients with HIV, suppressive anti-HSV therapy reduces the risk of both HSV-2 shedding and genital ulcer disease after initiation of HIV antiretroviral therapy, but it does not reduce the risk of HIV transmission to susceptible sex partners [64,65].

Pregnant women with genital herpes can transmit HSV-2 to the fetus or neonate during delivery via contact with lesions and/or vaginal secretions containing HSV. The virus is rarely transmitted transplacentally. Mothers of neonates with HSV infection tend to have newly acquired genital infection, often without symptoms at the time of delivery. Managing women with genital HSV acquired during late pregnancy requires specialist consultation [66].

During the third trimester, pregnant women without known genital or orolabial herpes should be advised to abstain from vaginal intercourse or receptive oral sex with partners with suspected genital or orolabial herpes, respectively. The efficacy of antiviral treatment to decrease or prevent HSV transmission to pregnant women by infected partners has not been studied. All pregnant women should be questioned about genital herpes history before and at the onset of labor. Patients with a known history of genital herpes should be assessed for prodromal symptoms and examined carefully for herpetic lesions during labor. Women without genital lesions or prodromal symptoms or signs can deliver vaginally. Cesarean delivery reduces but does not eliminate risk of HSV transmission to the neonate and may be considered for women with active outbreaks [1].

No adverse effects from oral or IV acyclovir to the fetus or newborn have been reported, and acyclovir is safe during breastfeeding and all pregnancy stages [67,68]. Safety data for prenatal exposure to valacyclovir and famciclovir are limited, but these agents probably pose a low risk. Third trimester antiviral prophylaxis significantly reduces the recurrence of genital herpes at delivery, the need for cesarean delivery due to genital herpes, and detection of HSV-2 at delivery, but it may not prevent transmission to neonates in all cases [69,70].

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].

Anogenital warts appear following an incubation period of one to six months and usually present as flat, papular, or pedunculated growths (often in clusters) on the genital mucosa. While usually asymptomatic, some patients experience itching, burning, pain, or discomfort [90].

Anogenital warts commonly occur around the vaginal introitus, under the foreskin of the uncircumcised penis, and on the shaft of the circumcised penis. Common sites in the anogenital epithelium or within the anogenital tract include the cervix, vagina, urethra, perineum, perianal skin, anus, and scrotum. Intra-anal warts are mostly observed in MSM and others who practice receptive anal intercourse, but they may occur in men and women without histories of anal sexual contact [90]. 


The clinical diagnosis of anogenital warts is made by visual inspection and confirmed with biopsy. Biopsy is indicated to rule out anogenital neoplasia if lesions are atypical (e.g., pigmented, indurated, affixed to underlying tissue, bleeding, ulcerated). Especially for patients with immunocompromise, biopsy is indicated when the diagnosis is uncertain; if lesions do not respond to standard therapy; or if the disease worsens during therapy. HPV testing is not recommended for anogenital wart diagnosis, because test results are not confirmatory and do not guide management [90].

Endocervical and anal warts can only be visualized by colposcopy and anoscopy. Visualization and detection of small warts is enhanced before colposcopy by applying a 3% to 5% acetic acid solution for several minutes, which causes the warts to whiten. This procedure should not be used to detect HPV infection [90].

Treatment can alleviate symptoms and emotional distress in some patients, particularly those with cosmetic concerns, and it resolves wart(s) in most patients, although it may take several attempts. If left untreated, anogenital warts may resolve spontaneously, remain unchanged, or increase in size or number. In immunocompetent people, genital warts may resolve without treatment within one year. For these patients, an acceptable option is deferred treatment to allow for spontaneous clearance. Available therapies for anogenital warts are intended to reduce, but not eradicate, HPV infectivity. Whether future transmission of HPV is decreased by treatment is unknown [1].

No treatment of genital warts is clearly more efficacious than others. Therapy selection is based on wart size, number, and anatomic site; patient preference; costs; convenience; adverse effects; and provider experience (Table 3). Some clinicians combine therapies, such as provider-administered cryotherapy along with patient-applied topical therapy [90].

Treatment involves topical therapy (mostly patient-applied) or provider-administered mechanical removal. Some patients prefer to apply treatment themselves for privacy reasons. To ensure patient-applied treatment is effective, all anogenital warts should be accessible and identified during the clinic visit, and patients should be instructed on proper application technique. Follow-up after several weeks allows providers to answer questions about medication use, address side effects, and assess treatment response [1].

Recommended Regimens for External Anogenital Warts

Recommended topical therapies for external anogenital warts include patient-applied imiquimod, an immune enhancer that stimulates production of interferon and other cytokines; podophyllotoxin, an antimitotic drug that causes wart necrosis; sinecatechins, a green tea extract with catechins the active constituent; and clinician-applied trichloroacetic acid (TCA) or bichloroacetic acid (BCA), caustic agents that destroy warts by chemical coagulation of proteins [90].

Soft, non-keratinized warts respond well to podophyllotoxin and TCA. Keratinized lesions are better suited for physical ablative methods such as cryotherapy, excision or electrocautery, or TCA. Imiquimod is suitable for both keratinized and non-keratinized warts. Patients with a low number of smaller warts can be treated with ablative therapy or topical podophyllotoxin from the outset. With patient-applied therapy, clinicians should provide a demonstration on lesion finding and treatment application. Very large wart lesions generally respond better to surgical treatment [90]. 


Patient-applied treatments differ in recommended application and possible side effects. Imiquimod is applied three times per week (5% cream) or daily (3.75% cream) at bedtime for up to 16 weeks. Local reactions can include redness, irritation, induration, ulceration/erosions, or vesicles, and imiquimod may worsen psoriasis, vitiligo, and other inflammatory or autoimmune skin diseases [91,92,93,94].

Podophyllotoxin is applied twice daily for three days, followed by four days without therapy; this is repeated for up to four cycles. Mild-to-moderate pain or local irritation may develop [90].

Sinecatechins is applied three times daily for up to 16 weeks [95]. Patients should be advised to avoid sexual contact with treated areas during therapy. Common side effects are erythema, pruritus/burning, pain, ulceration, edema, induration, or vesicular rash. Safety and efficacy is not known in patients with genital herpes or HIV and other immune-impaired conditions [96].

TCA and BCA are widely used but have not been studied extensively. A small amount is applied to the warts and allowed to dry before the patient sits or stands. Treatment can be repeated weekly, if needed [1].

Mechanical removal options include cryotherapy, electrocauterization, and laser or surgical excision. Cryotherapy employs thermal-induced cytolysis for wart destruction and requires proper training to avoid over- or undertreatment and resultant complications or inefficacy. Pain is common following liquid nitrogen treatment from necrosis or blistering, and local anesthesia can help facilitate therapy [1].

Surgical therapy can eliminate most warts in a single visit, but recurrence may occur. After local anesthesia is applied, anogenital warts are physically destroyed by electrocautery, and no additional hemostasis is required. Warts can also be removed by tangential excision with a pair of fine scissors or scalpel, by carbon dioxide (CO2) laser, or by curettage. Because most warts are exophytic, the wound is not deeper than the upper dermis. Hemostasis can be achieved with an electrocautery unit or, in cases of very minor bleeding, a chemical styptic (e.g., an aluminum chloride solution). Most cases do not need suturing. As noted, with large or extensive warts, surgical therapy, including CO2 laser, is most beneficial, especially for intraurethral warts and in patients lacking response to other treatments [90].

Alternative Regimens

Alternative approaches for anogenital warts have less supportive data and potentially greater side effects. Options include podophyllin resin, intralesional interferon, photodynamic therapy, and topical cidofovir. Patient-applied podophyllin resin is no longer recommended because of potentially severe systemic toxicity; however, provider-administered podophyllin resin 10% to 25% may be considered with strict adherence to recommended use [1,97,98].

Change to a new treatment modality is indicated if the patient fails to show substantial improvement or experiences severe side effects. Complications are rare when treatment is administered properly, but persistent hypo- or hyperpigmentation can occur with cryotherapy, electrocautery, and imiquimod cream. Depressed or hypertrophic scars are uncommon but can occur, especially with insufficient healing time between treatments. Rarely, treatment can result in chronic pain syndromes such as vulvodynia, hyperesthesia of the treatment site, or painful defecation or fistulas (with anal warts) [1].

Podophyllotoxin, podophyllin, and sinecatechins should not be used during pregnancy. Imiquimod appears to pose low risk but should be avoided until more data are available. Anogenital warts can proliferate and become friable during pregnancy, and although removal of warts can be considered, resolution might be incomplete or poor until pregnancy is complete.

Rarely, HPV types 6 and 11 can cause respiratory papillomatosis in infants and children, although the route of transmission is not completely understood. Whether cesarean delivery prevents respiratory papillomatosis in offspring is also unclear, and cesarean delivery should not be performed solely to prevent transmission of HPV. Cesarean delivery is indicated for women with anogenital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding. Pregnant women with anogenital warts should be counseled about the low but present risk for warts on the larynx of their infants or children (recurrent respiratory papillomatosis) [1,99].

Patients with HPV who have HIV infection or are immunosuppressed are more likely to develop anogenital warts, to present with larger or more numerous lesions, to lack treatment response, and to have more frequent recurrences after treatment [100,101]. Despite this, treatment should not be altered for patients with HIV. Squamous cell carcinomas inside of, or resembling, anogenital warts are more frequent in immunosuppressed patients, requiring biopsy for diagnostic confirmation in suspicious cases [102,103]. Biopsy of an atypical wart might reveal high-grade squamous intraepithelial lesions or cancer of the anogenital tract. In this instance, specialist referral for treatment is recommended [1].

More than 70% of adults are symptomatic during acute HAV infection, but most children are asymptomatic or have mild, nonspecific symptoms and little or no jaundice [1]. Most symptomatic patients follow a clinical course of a prodromal phase, icteric illness, and recovery. Rarely, patients may develop fulminant infection during acute HAV infection [105].

Prodromal Illness

After an average 28-day incubation (range: 15 to 45 days), patients can experience nonspecific flu-like symptoms (e.g., malaise, myalgia, fatigue), often with right upper abdominal pain. This phase lasts 3 to 10 days.

Icteric Illness

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.

In patients with acute HAV infection, acute liver failure develops in 0.4%, but 15% may require hospital care. The overall mortality is <0.1%, which rises to 40% with acute liver failure; these patients should be considered for liver transplantation [105].

Diagnosis of HAV infection requires serologic testing [1,105]. Diagnosis is confirmed by positive serum anti-HAV IgM, which usually remains positive for 45 to 60 days. As noted, HAV-IgG does not distinguish current from past infection and remains positive for life.

Most patients with symptomatic acute HAV infection are managed as outpatients, with emphasis on rest and oral hydration. Hospitalization is necessary for patients who become dehydrated from nausea and vomiting or who have signs of hepatic encephalopathy (e.g., drowsiness, somnolence, confusion). Medications that may damage, or are metabolized by, the liver should be used with caution in persons with HAV infection [1,105].

Vaccination is the most effective means of preventing HAV transmission among persons at risk for infection. HAV vaccines are prepared from formalin-inactivated, cell-culture-derived HAV. Two monovalent vaccines (Havrix and VAQTA) are FDA-approved for persons 12 months of age or older [1,109].

HAV vaccines are given IM in a two-dose series at 0 and 6 to 18 months. Protective antibody levels are induced in 94% to 100% of adults by one month after the first dose, and in 100% after the second dose. Kinetic models of antibody decline indicate that protective antibody levels persist for more than 20 years [109].

HAV vaccine should be offered to the following persons seeking STI services [1]:

A combined HAV/HBV vaccine (Twinrix) is FDA-approved for use as a three-dose series in adults 18 years of age or older at risk for hepatitis A and hepatitis B infections. When administered IM on a 0-, 1-, and 6-month schedule, the vaccine has equivalent immunogenicity to that of the monovalent vaccines [110,111,112].

Pre-Vaccination Serologic Testing

Around one-third of the U.S. population has serologic evidence of previous HAV infection, and prevalence increases with age. The potential cost savings of pre-vaccination susceptibility testing should be weighed against the cost and probability that testing will interfere with initiating vaccination. Serologic testing should not be a barrier to vaccination of at-risk populations, and vaccinating a person already immune is not harmful. When a history of at least two-dose HAV vaccination is documented, no further vaccination or serologic testing is needed [113].

When given within two weeks of HAV exposure, intramuscular (IM) immunoglobulin is more than 85% effective in preventing HAV infection [114]. Persons exposed to HAV who have not previously been vaccinated should receive a single dose of monovalent hepatitis A vaccine or immunoglobulin (0.02 mL/kg) as soon as possible; efficacy is not established more than two weeks post-exposure [109]. There is limited information on vaccine versus immunoglobulin post-exposure efficacy, and no data are available on patients older than 40 years of age or with medical comorbidities. The decision to use the vaccine versus immunoglobulin should be informed by patient risk for more severe HAV infection (e.g., older age, chronic liver disease) and HAV transmission risk from the exposure [109].

Immunoglobulin is preferred for prophylaxis in children younger than 12 months of age, patients with immune compromise or chronic liver disease, and when vaccination is contraindicated. Immunoglobulin is also preferred for persons older than 40 years of age, due in part to the greater severity of hepatitis A in this age group. In these cases, the vaccine can be used if immunoglobulin cannot be obtained [109]. For healthy persons 1 to 40 years of age, the vaccine is preferred to immunoglobulin because of the advantages in long-term protection and ease of use [1]. The combined HAV/HBV vaccine may be considered in eligible persons [1].

It is crucial that all patients with diagnosed HAV infection receive information and counseling [105]. Clinicians should provide detailed explanations verbally and in writing, with emphasis on long-term health implications for the patient and partner(s). Pregnant women should be advised of the increased risk of miscarriage/premature labor and the importance of seeking medical advice if symptoms develop. All patients should exercise care whenhandling food and avoid unprotected sexual intercourse until they are considered noninfectious. Partner notification is necessary for at-risk sexual contacts (oro-anal, digital/rectal, or penetrative anal sex) within two weeks before and up to one week after the onset of jaundice.

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].

Routes of HBV transmission include [36,105,115]:

Signs and symptoms of patients in the prodromal and icteric phases of acute HBV infection are similar to hepatitis A but can be more severe and prolonged in symptomatic patients. Acute HBV infection is asymptomatic in almost all infants and children and in 10% to 50% of adults [105].

Chronic HBV infection usually occurs without physical signs, but some patients may develop fatigue or loss of appetite. After years of infection, signs of chronic liver disease may develop, including spider nevi, finger clubbing, jaundice, and hepatosplenomegaly. Severe cases can develop thinning skin, bruising, ascites, asterixis ("liver flap"), and encephalopathy [116].

Acute liver failure occurs in less than 1% of symptomatic acute cases; prognosis is worse than in hepatitis A. Pregnant women have increased rates of miscarriage/premature labor and risk of vertical transmission. Mortality is less than 1% in acute infection [116].

Chronic infection (longer than six months) occurs in 5% to 10% of symptomatic patients. Risk is inversely related to age when infected; chronic HBV infection develops in roughly 90% of those infected as infants, 25% to 50% infected before the age of 5 years, and 5% of those infected as adults [117]. Risk of premature death from cirrhosis or hepatocellular carcinoma is 15% to 25% with chronic HBV infection [116,117].

Diagnosis of acute or chronic HBV infection requires serologic testing [1,117]. Antibody to hepatitis B surface antigen (HBsAg) is present in acute and chronic infection; the presence of IgM antibody to hepatitis B core antigen (IgM anti-HBc) is diagnostic of acute or recently acquired HBV infection. Antibody to HBsAg (anti-HBs) persists after infection has resolved and is the HBV antibody marker used to verify vaccination. Presence of HBsAg and total anti-HBc, with a negative test for IgM anti-HBc, indicates chronic HBV infection. Presence of anti-HBc alone can reflect acute, resolved, or chronic infection or a false-positive result.

All persons with confirmed HBsAg should be reported to the state or local health department. In addition, patients with HBsAg should be retested to assess chronic HBV infection, confirmed by the absence of IgM anti-HBc or the persistence of HBsAg for six months.

In patients with severe acute HBV infection, antiviral agents can prevent acute liver failure and improve morbidity and mortality [105,117]. Otherwise, treatment is supportive for patients with acute HBV. Patients with chronic HBV should receive specialist management. Drugs FDA approved for treating chronic hepatitis B can achieve durable suppression of HBV replication and remission of liver disease [1,117,118].

The national strategy for eliminating transmission of HBV infection includes [117,119,120]:

High vaccination rates and subsequent declines in the incidence of acute HBV infection have been achieved in infants and adolescents [120,121]. In addition, the aging of vaccinated children and adolescents has likely led to improved vaccination coverage and lower acute HBV infection rates in adults younger than 30 years of age [122]. However, coverage of adults 30 years of age and older in high-risk groups (e.g., multiple sex partners, MSM, IDUs) remains low, and these groups account for the highest rates of preventable acute infections [119,123]. Settings that provide STI services should vaccinate those who are unvaccinated, as adults seeking STI services are considered at increased risk for HBV infection.

Two FDA-approved agents are available for HBV prevention: hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) [119,120]. HBIG protects for three to six months against HBV infection and is used in post-exposure prophylaxis as an adjunct to hepatitis B vaccination (in unvaccinated persons) or in persons without vaccine response.

Hepatitis B vaccine contains HBsAg produced in yeast by recombinant DNA and is effective for prevention of HBV infection as pre-exposure vaccination and post-exposure prophylaxis. Available monovalent hepatitis B vaccines are [117]:

Pediarix is a combination HBV/diphtheria, tetanus, DTaP, and IPV vaccine for infants 6 weeks to 7 years of age; Vaxelis is a similar product for children birth to 4 years of age [117]. As discussed, Twinrix is a combination HAV/HBV vaccine for patients 18 years of age or older.

Hepatitis B vaccines differ by vaccination schedule; some require three injections over 4 or 6 months, while others require four injections over 12 months. Selection should consider the need to achieve completion of the vaccine series and likelihood of extended follow-up [1].

In adolescents and healthy adults younger than 40 years of age, 30% to 55% achieve a protective antibody response (i.e., anti-HBs ≥10 mIU/mL) after the first vaccine dose, 75% after the second, and more than 90% after the third. Vaccine-induced immune memory is demonstrated to persist for at least 30 years [117]. Periodic testing to determine antibody levels is not necessary, and booster doses of the vaccine are not currently recommended [121,124,125].

Hepatitis B vaccination is generally well tolerated by most patients; injection-site pain and low-grade fever are reported in a minority. In children and adolescents, anaphylaxis has been reported in 1 patient for every 1.1 million vaccines, but no deaths have been reported in these patients. Hepatitis B vaccination is contraindicated in patients with previous anaphylactic reaction to the vaccine itself or any vaccine component. No other adverse events with hepatitis B vaccine have been demonstrated [119,120].

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

As noted, hepatitis B vaccine should be routinely offered to all unvaccinated persons attending STI clinics and those seeking STI evaluation or treatment in correctional facilities, drug-abuse treatment and prevention programs, federally qualified health centers, and settings that serve MSM.

Pre-Vaccination Serologic Testing

Pre-vaccination serologic testing for susceptibility to HBV may reduce the costs of completing the vaccine series in populations with a high prevalence of HBV infection (e.g., older IDUs, MSM). Susceptibility testing is recommended for the unvaccinated household, sexual, and needle-sharing contacts of HBsAg-positive persons. Vaccination of those immune to HBV due to current/past infection or vaccination is not harmful and does not increase the risk for adverse events [123].

Anti-HBc is the test of choice for pre-vaccination testing, and those who test anti-HBc-positive should be tested for HBsAg. If HBsAg negative, no further action is required. Persons who are HBsAg-positive should be referred to a specialist in hepatitis B infection management [1].

Post-Vaccination Serologic Testing for Response

Post-vaccination serologic testing for immunity is not necessary after routine vaccination of most healthy adolescents or adults. Such testing is recommended for persons whose clinical management depends on confirming their immune status, including healthcare and public safety workers at high risk for exposure to blood or body fluids. Post-vaccination testing is also recommended for persons with HIV and other immunocompromising conditions and sex and needle-sharing partners of HBsAg-positive persons. If indicated, anti-HBs testing should be performed one to two months after the last dose of the vaccine series [1].

Passive-active post-exposure prophylaxis (i.e., HBIG plus HBV vaccine at separate IM sites) and active post-exposure prophylaxis (i.e., hepatitis B vaccination alone) are both highly effective in preventing transmission after exposure to HBV. HBIG alone is effective in preventing HBV transmission, but it is typically combined with hepatitis B vaccine.

Unvaccinated persons should receive HBIG plus hepatitis vaccine as soon as possible (within 24 hours) after exposure to blood or body fluids from a person with known HBsAg, and the full HBV vaccine series should be completed. Persons exposed during the vaccine process should receive HBIG and complete the series [126].

Unvaccinated persons exposed to blood or body fluids from a person with unknown HBsAg status should receive the hepatitis B vaccine series, with the first dose initiated preferably less than 24 hours after exposure [126].

According to the American Association for the Study of Liver Diseases, patients with hepatitis B should be counseled regarding transmission to others. For casual sex partners or steady partners who have not been tested or have not completed the full immunization series, barrier protection methods should be utilized.

(https://journals.lww.com/hep/Fulltext/2018/04000/Update_on_prevention,_diagnosis,_and_treatment_of.34.aspx Last Accessed: June 14, 2023)

Level of Evidence: Expert Opinion/Consensus Statement

Sex partners of patients with HBV infection should be advised to use latex condoms for protection from sexual exposure unless they demonstrate immunity post-vaccination (anti-HBs ≥10 mIU/mL) or from previous infection (anti-HBc positive). To minimize transmission risk to others through infected blood or bodily fluids, patients with HBV should:

In addition, to protect the liver from further harm, patients with HBV are advised to: 


When seeking medical or dental care, patients should disclose their HBsAg status so they can be appropriately evaluated and managed.

HBV is not usually spread by hugging, coughing, contaminated food or water, shared eating utensils or drinking glasses, or casual contact. It is important that patients with HBV not be excluded from work, school, play, childcare, or other settings because of their infection. Support group involvement can help patients cope with chronic HBV infection.

Regardless of previous testing or vaccination, all pregnant women should be tested for HBsAg at the first prenatal visit. Those at high risk should also be tested at delivery and receive hepatitis B vaccination. All pregnant women with HBsAg should be reported to state and local perinatal hepatitis B prevention programs and referred to a specialist [1].

HIV infection and other immune suppressing conditions can impair hepatitis B vaccine response. Persons with HIV infection should be tested for anti-HBs one to two months after the third vaccine dose. Modified dosing regimens, including doubling the standard antigen dose and adding additional doses, might increase the response rate [1].

In 2012, the FDA approved the first medication for the prevention of sexually transmitted HIV infection, the combination drug Truvada (emtricitabine/tenofovir DF) [142]. In 2019, another combination drug—Descovy (emtricitabine/tenofovir)—was approved to prevent HIV infection [143]. In 2021, the FDA approved the first injectable agent for the prevention of HIV infection; cabotegravir is given first as two initiation injections administered one month apart, and then every two months thereafter [76]. In conjunction with safer sex practices, these agents have been found to be partially effective as pre-exposure prophylaxis in high-risk patients. The Chemoprophylaxis for HIV Prevention in Men study, also known as iPrEx, studied the effect of once daily Truvada in 2,499 HIV-seronegative men or transgender women who have sex with men compared with placebo [144]. Researchers found that persons receiving Truvada experienced a 44% reduction in the incidence of HIV after a median of 1.2 years compared with placebo. Pre-exposure prophylaxis was most effective among participants at particularly high risk for HIV (i.e., self-reports of unprotected receptive anal intercourse). Research has indicated that Descovy and cabotegravir are similarly effective [143].

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]:

Prophylaxis is also recommended for high-risk heterosexual adults who have had sex with an opposite sex partner(s) in the past six months, and are not in a monogamous partnership with a recently tested, HIV-negative partner, and have one of the following risk factors [145]:

IDUs are also considered candidates for pre-exposure prophylaxis if they meet certain criteria. The guideline states that persons who have injected drugs not prescribed by a clinician in the past six months may be candidates for prophylaxis if they also are positive for one of the following factors [145]:

Injection cabotegravir given bimonthly and fixed-dose combination tenofovir and emtricitabine (Truvada or Descovy) taken daily are approved for pre-exposure prophylaxis, and they are considered the recommended first-line option [142,145]. However, because tenofovir alone has been proven effective in trials with IDU and heterosexually active men and women, it is the alternative option for these populations [145]. No other antiretroviral regimens should be used for pre-exposure prophylaxis.

All patients prescribed pre-exposure prophylaxis must have a negative HIV test prior to initiating treatment and every three months thereafter. In addition, patients should be advised regarding possible side effects and the continued necessity for safe sex practices. Eligible patients should also be screened for hepatitis B and have a confirmed creatinine clearance of 60 mL per minute or greater [145].