Update on Sexually Transmitted Diseases and HIV

Release Date: August 1, 2011

Expiration Date: August 31, 2013

FACULTY:

Allana J. Sucher, PharmD, BCPS
Associate Professor of Pharmacy Practice
Regis University School of Pharmacy
Denver, Colorado

Lisa D. Inge, PharmD, BCPS, AAHIVE
Assistant Director, Jacksonville Campus
Clinical Associate Professor of Pharmacotherapy & Translational Research
University of Florida, College of Pharmacy
Shands Jacksonville Medical Center
Jacksonville, Florida

Brandon J. Sucher, PharmD, CDE, AE-C
Associate Professor of Pharmacy Practice
Regis University School of Pharmacy
Denver, Colorado

FACULTY DISCLOSURE STATEMENTS:

Drs. Allana Sucher, Lisa Inge, and Brandon Sucher have no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-11-020-H02-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To provide pharmacists with the knowledge necessary to appropriately manage patients infected with sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV).

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Discuss strategies to prevent the spread of STDs, including HIV.
  2. Identify the most common etiologies of STDs.
  3. Recognize the clinical presentation of STDs.
  4. Recommend an appropriate antimicrobial agent or regimen for the treatment of STDs, including antiretroviral therapy for HIV.
  5. Counsel a patient who is receiving treatment for an STD.

The spectrum of sexually transmitted diseases (STDs) encompasses a variety of pathogens that are spread by sexual contact. STDs remain a major public health challenge, as evidenced by information from the Centers for Disease Control and Prevention (CDC), which estimates that 19 million new infections are caused by STDs each year, costing the U.S. health care system over $16 billion annually.1

Guidelines for the treatment of STDs and human immunodeficiency virus (HIV) in adolescents and adults were recently updated.2,3 This article focuses on these guidelines and reviews the current etiology, diagnostic strategies, and treatment choices for the management of syphilis, trichomoniasis, gonorrhea, chlamydia, genital herpes, human papillomavirus (HPV), and HIV.

Prevention

Per the CDC, a reliable way to avoid STDs is to abstain from oral, vaginal, and anal sexual activity or to be in a long-term, mutually monogamous relationship with an uninfected partner. For persons about to enter into a mutually monogamous relationship, partners may discuss screening for STDs prior to the initiation of sex. Although consistent and correct use of latex condoms is important, they cannot provide complete protection against diseases such as herpes, syphilis, and genital warts that are spread outside the area that a condom covers. Finally, pre-exposure vaccination against HPV is one of the most important ways of preventing this particular STD.2

Syphilis

Syphilis is a bacterial infection caused by the spirochete Treponema pallidum.4 It is classified by different stages based on clinical findings (TABLE 1), which are used to help guide treatment. Although symptoms of primary and secondary syphilis will eventually resolve without treatment, antibiotic therapy is necessary to prevent progression to a later stage of infection.2,4,5

tbl1

Diagnostic Tests: A dark-field microscope can be used to examine material from a chancre, with the presence of T pallidum indicating infection. There are two types of serologic blood tests (treponemal and nontreponemal) that may also be used for diagnosis. Treponemal tests include fluorescent treponemal antibody absorbed (FTA-ABS), enzyme immunoassays (EIAs), and the T pallidum passive particle agglutination (TP-PA). If positive, these tests will remain positive, and should not be used to assess disease activity or treatment response. Nontreponemal tests include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests and are reported in antibody titers. Since these titers correlate with disease activity, a change in two dilutions (example from 1:16 to 1:4 or 1:8 to 1:32) is considered significant. Typically, a treponemal screening test is used first; if positive, a nontreponemal test is performed, with titers used to assess the patient’s response to treatment.2,4,6

Treatment: Parenteral penicillin G is the preferred treatment for all stages of syphilis. The treatment of choice for primary, secondary, or early latent syphilis is benzathine penicillin G 2.4 million units IM as a one-time dose. A patient’s nontreponemal titers should be rechecked in 6 months; if titers have not declined by two dilutions, treatment should be extended to 2.4 million units IM weekly for 3 weeks. Alternatives for those allergic to penicillin include doxycycline 100 mg po bid for 14 days or ceftriaxone 1 g IV daily for 14 days.2

The treatment of choice for tertiary and late latent syphilis or for syphilis of an unknown duration is benzathine penicillin G 2.4 million units IM weekly for 3 weeks. An alternative for penicillin-allergic patients is doxycycline 100 mg po bid for 28 days.2

As parenteral penicillin G is the only agent with documented efficacy for the treatment of syphilis during pregnancy, all pregnant women should be desensitized and treated with penicillin according to their stage of infection.2

All patients with neurologic symptoms should be evaluated for neurosyphilis with a cerebrospinal fluid examination. Additionally, some providers will assess all HIV-positive patients who have an RPR titer >1:32 for neurosyphilis. The treatment of choice for neurosyphilis is aqueous penicillin G 3 to 4 million units IV every 4 hours or as a continuous infusion for 10 to 14 days. For those who are allergic to penicillin, desensitization is recommended.2

The most common adverse reaction in patients with syphilis treated with penicillin is the Jarisch-Herxheimer reaction. This is not a drug allergy, but a reaction characterized by acute fever, headache, and/or myalgias. Patients should be counseled about this possible reaction, which usually occurs within 24 hours after the initiation of therapy and can be managed with antipyretics. Women who experience the Jarisch-Herxheimer reaction during the second half of pregnancy are at an increased risk for premature labor and fetal distress, and should be counseled to contact their physician immediately if this reaction occurs.2

Sexual partners of infected patients should be considered at risk and provided treatment if they have had sexual contact with the patient within 3 months of the diagnosis of primary syphilis, 6 months of the diagnosis of secondary syphilis, and 1 year of the diagnosis of early latent syphilis.2

Trichomoniasis

Trichomoniasis is caused by the protozoan Trichomonas vaginalis. It is considered to be the most common curable STD worldwide in young, sexually active women. Women with trichomoniasis usually have a frothy, yellow-green vaginal discharge with a strong odor. Other symptoms may include discomfort during urination or intercourse, irritation or itching of the genital area, and lower abdominal pain. Most men with trichomoniasis do not have signs or symptoms, while some may have temporary penile irritation, mild discharge, or burning after urination or ejaculation.2,4,7

Diagnostic Tests: Because of the high prevalence, it is recommended to test for T vaginalis in all women seeking medical care for vaginal discharge. There are several diagnostic tests available, including microscopic examination or culture of vaginal secretions for T vaginalis or a point-of-care rapid test of vaginal secretions. A pelvic examination may show small red ulcers on the vaginal wall or cervix. In men, culture or polymerase chain reaction (PCR) testing of a urethral swab, urine, or semen is a diagnostic option.2

Treatment: Nitroimidazoles are the only class of drugs useful for the treatment of trichomoniasis. The recommended treatment is either metronidazole or tinidazole given 2 g orally as a single dose. If treatment failure occurs after the aforementioned regimen of metronidazole, it is recommended to treat the patient with metronidazole 500 mg orally twice daily for 7 days. If this regimen is not successful, it is recommended to give either metronidazole or tinidazole at a dosage of 2 g orally daily for 5 days.2

Patients should be counseled to take metronidazole immediate-release tablets or tinidazole with food to minimize gastrointestinal (GI) upset. In addition, patients receiving either agent should be counseled to avoid alcohol during treatment and to continue to avoid it for 24 hours after metronidazole therapy or 72 hours after tinidazole.2,8

All sexual partners of those diagnosed with T vaginalis should be treated, and patients should abstain from sex until both they and their partners have finished therapy and are asymptomatic.2

Gonorrhea

Gonorrhea, caused by the aerobic, gram-negative coccus Neisseria gonorrhoeae, may involve asymptomatic or symptomatic infections.2 If present, signs and symptoms of infection in women include a painful or burning sensation when urinating, increased vaginal discharge, or vaginal bleeding between periods. In men, symptoms include a burning sensation when urinating, or a white, yellow, or green discharge from the penis. Symptoms of rectal infection in both genders include discharge, anal itching, soreness, bleeding, or painful bowel movements. If untreated, gonorrhea can lead to epididymitis or infertility in men and pelvic inflammatory disease, infertility, or ectopic pregnancy in women. Gonorrhea may also spread to the blood or joints in men and women.2,4,9

Diagnostic Tests: The diagnosis of infection with N gonorrhoeae can be made by checking endocervical, vaginal, or urine specimens with culture or nucleic acid amplification testing. In men, a Gram’s stain of a urethral specimen may also be performed.2

Treatment: It is important to note that patients infected with N gonorrhoeae are frequently co-infected with Chla mydia trachomatis (discussed in the next section); thus, patients treated for a gonococcal infection should also be initially treated with a regimen that is effective against uncomplicated genital chlamydia.2

Recommended treatment regimens for uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx are listed in TABLE 2. For disseminated gonococcal infections (in the bloodstream or at a site distant from uncomplicated infections), the recommended regimen is ceftriaxone 1 g IM or IV daily for 24 to 48 hours after the patient clinically improves, followed by cefixime 400 mg orally twice daily to complete at least 1 week total of antimicrobial therapy. For those who have a severe penicillin or cephalosporin allergy, azithromycin 2 g orally as a single dose or a fluoroquinolone may be tried, but the use of these agents should be limited because of the risk of resistance.2

tbl2

Intramuscular ceftriaxone may cause local induration, warmth, or skin tightness. Patients should be counseled to report any signs of rash. Azithromycin or doxycycline may cause nausea and/or diarrhea, which may be minimized by taking the agent with food. In addition, patients receiving doxycycline may be more sensitive to sunlight and should be counseled to avoid direct exposure and to use sunblock.8

Sexual partners from within 60 days prior to the onset of the patient’s symptoms or diagnosis of gonorrhea should be evaluated and treated for N gonorrhoeae and C trachomatis. If the patient’s most recent sexual intercourse was more than 60 days prior, it is recommended to treat the patient’s last sex partner. To minimize disease transmission of chlamydia to sex partners, patients should abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen.2

Chlamydia

Chlamydia genital infection, caused by the atypical bacterium Chlamydia trachomatis, has the highest prevalence in those ≤25 years of age. Chlamydia is known as a “silent” disease because asymptomatic infection is common among both men and women.2,10

Chlamydia causes essentially the same signs and symptoms as gonorrhea in both women and men. Untreated chlamydia in women can cause pelvic inflammatory disease, ectopic pregnancy, or infertility, while complications of untreated infection in men (such as epididymitis or sterility) are rare.2,10

Diagnostic Tests: The CDC recommends annual screening of all sexually active women aged ≤25 years or those >25 years of age with risk factors, such as new or multiple sex partners. Diagnosis of C trachomatis may be performed by cell culture or nucleic acid amplification testing of urine or swab specimens from the endocervix or vagina in women and the urethra in men.2,11

Treatment: The recommended regimen for the treatment of chlamydia is azithromycin 1 g orally as a one-time dose or doxycycline 100 mg po bid for 7 days. (Counseling points for these agents have been covered in the previous section.) Alternative regimens include a 7-day course of either erythromycin 500 mg po every 6 hours or levofloxacin 500 mg po daily.2 The evaluation and management of sexual partners is the same as for gonorrhea.2

Genital Herpes

Genital herpes is caused by two types of herpes simplex virus (HSV), HSV-1 and HSV-2.2 Symptoms of genital herpes include painful, ulcerative, itchy lesions, painful urination, and vaginal or urethral discharge. In addition, patients commonly have systemic symptoms of fever, headache, or malaise and a prodrome of flulike symptoms, genital pain, or genital tingling prior to the outbreak of lesions. It is important to note that most people infected with HSV-2 have mild or unrecognized symptoms but continue to shed virus intermittently in the genital tract. Thus, the majority of genital herpes infections are spread by persons unaware that they are infected.4,12

Diagnostic Tests: Clinicians may diagnose genital herpes by visual inspection, but this should be confirmed by laboratory testing. There are two types of laboratory tests for HSV. Virologic tests use cell culture and PCR assays from genital ulcers or mucocutaneous lesions, while serologic tests are blood tests (both laboratory-based and point-of-care tests) that detect antibodies to HSV-specific glycoprotein G2 (for HSV-2) and glycoprotein G1 (for HSV-1).2,4

Treatment: Systemic antivirals can partially control the signs and symptoms of herpes when used to treat clinical and recurrent episodes or when used daily as suppressive therapy. However, it is important for the clinician to counsel the patient that antivirals do not eradicate the virus. The three antiviral agents with randomized trials that show clinical benefit for genital herpes are acyclovir, valacyclovir, and famciclovir. Topical therapy offers minimal clinical benefit and should not be used for the management of genital herpes.2 Since patients with a first episode of herpes can develop severe or prolonged symptoms, all patients with first episodes should receive antiviral therapy, started within 72 hours of the onset of symptoms (TABLE 3).2,13

Almost all persons with symptomatic first-episode HSV-2 infection will experience recurrent episodes of genital lesions, while genital recurrences are less frequent for those initially infected with HSV-1. There are several different antiviral dosing regimens and durations of therapy for the episodic treatment of recurrent genital herpes (TABLE 3). It is important to note that medications should be initiated within 24 hours of the onset of symptoms. Thus, patients are usually prescribed a supply of medications to keep at home, with instructions to initiate therapy immediately after the onset of symptoms or during the prodrome period.2

Daily suppressive therapy (TABLE 3) should be considered in those with frequent recurrences, defined as 6 or more episodes per year. The antiviral medication should be discontinued after 1 year and the patient evaluated for the frequency of recurrences to assess the need for continued use. Treatment with valacyclovir 500 mg orally daily has also been shown to decrease the rate of HSV-2 transmission between discordant heterosexual couples.14 Such couples should be encouraged to consider daily suppressive therapy (no matter how many outbreaks the infected partner experiences each year) in addition to consistent condom use.2

tbl3

Patients receiving acyclovir, valacyclovir, or famciclovir may experience nausea, headache, or dizziness and should be counseled to maintain adequate hydration, to use caution when engaging in tasks that require alertness (until effects are known), and to take the agent with food to minimize GI effects.8 Patients with complications of HSV that necessitate hospitalization should receive IV acyclovir. Finally, in those patients with persistent or recurrent lesions while receiving the proper dosage of antiviral treatment, “cyclovir”-resistant (i.e., acyclovir, famciclovir, valacyclovir) HSV should be suspected. In these cases, foscarnet or cidofovir (both IV) may be used.2

Sexual partners of those with genital herpes can benefit from both evaluation and counseling. Symptomatic partners should be evaluated and treated in the same manner as their infected partner; asymptomatic partners should be offered serologic testing for HSV infection.2

Human Papillomavirus

Of the more than 100 types of HPV that exist, over 40 can infect the genital area, with most infections remaining asymptomatic or subclinical. HPV types 16 and 18 are considered high-risk HPV types because they cause 70% of cases of cervical cancer, in addition to being associated with anal, penile, vulvar, and vaginal cancers. HPV types 6 and 11 are considered low-risk types because they do not cause cancer; however, these types are responsible for 90% of cases of genital warts. Genital warts are usually asymptomatic but may be painful or pruritic.2,4

Diagnostic Tests: HPV tests to detect viral nucleic acid or capsid protein are available for women >30 years of age undergoing cervical cancer screening. A pap smear may be performed to assess for cell abnormalities on the cervix. Clinicians can diagnose genital warts based on clinical presentation, and for those cases in which the diagnosis is uncertain, a biopsy may be performed.2,15

Vaccines: Pre-exposure vaccination is one of the most effective methods for preventing transmission of HPV. There are two available HPV vaccines—the quadrivalent vaccine Gardasil, which offers protection against HPV types 6, 11, 16, and 18, and the bivalent vaccine Cervarix, which protects against HPV types 16 and 18. Both Gardasil and Cervarix are indicated in females between the ages of 9 and 26 years for the prevention of cervical cancer. Gardasil is also indicated in males and females between the ages of 9 and 26 years for the prevention of genital warts.2,16

Treatment: The main reasons for treating genital warts are to improve symptoms and relieve cosmetic concerns. If left untreated, genital warts may resolve on their own, remain unchanged, or increase in size or number. Therapy should be guided by patient preference and health care provider experience, as no one treatment has been shown to be superior to another (TABLE 4).2

tbl4

HIV

Epidemiology: As HIV/AIDS enters into the fourth decade since its identification in the U.S., the virus still infects one American every 9.5 minutes.17 An estimated one million Americans are living with HIV, and 1 in 5 remains unaware of their status.18 Approximately 18,000 people in the U.S. still die each year from the disease.18

Testing: In 2006, the CDC recommended routine HIV testing for all persons aged 13 to 64 years at least once in their lifetime, with testing more often for those with risk factors for transmission.19 To date, the institution of this practice has been limited at best.20 In 2010, the FDA approved a 60-second HIV test, which may increase ease of use and patient receipt of test results in a variety of patient care settings. The sensitivity and specificity of this test are 99.8% and 99.5%, respectively.21

Initiation of Antiretroviral (ARV) Therapy: The Department of Health and Human Services (HHS) has issued updated HIV treatment guidelines that state that ARV therapy should be initiated in all persons who have a CD4+ T-cell count of <350 cells/mm3 or an AIDS-defining illness or opportunistic infection. ARVs should also be initiated in all pregnant women with HIV, in those requiring hepatitis B treatment, and in individuals with HIV-associated nephropathy. Furthermore, a rapid decline in CD4+ T cells of >100 cells/mm3 per year or an HIV RNA (viral load [VL]) that exceeds 100,000 copies/mL should trigger some urgency to start ARV therapy to prevent additional immune system damage.3

The guidelines also recommend starting ARV therapy in patients with CD4+ T-cell counts of <500 cells/mm3, as this may decrease mortality. However, data are currently insufficient to definitively support this recommendation, as it was obtained from cohort studies. Furthermore, the guidelines address the possibility of starting ARVs in patients with a CD4+ count of >500 cells/mm3 who are ready to make the lifelong commitment to ARV. Treatment of this population may not only offer public health benefits by decreasing transmission (from reducing the VL), but may also prevent additional disease complications (e.g., cardiovascular disease, HIV-associated nephropathy, or liver damage) associated with the inflammatory response to the virus. There has also been a proven benefit to starting ARV therapy in HIV-positive patients with a CD4+ count of >500 cells/mm3 who have been diagnosed with a malignancy.3 The limitations of starting ARV therapy early include the unknown risks associated with an even longer duration of therapy, the likelihood of drug resistance to develop due to lack of adherence or to pharmacokinetic alterations (as a result of drug or herbal interactions), and the potential cost to both the patient and society.3

Selection of Therapeutic Agents: The HHS guidelines recommend specific, preferred ARV regimens for treatmentnaïve patients (TABLE 5). Selection criteria are based on a variety of factors including potency, administration frequency, potential toxicity, and tolerability. However, ARV therapy must be individualized based on resistance testing, potential contraindications and drug interactions, adherence factors (e.g., number of pills, size of pills, food and fluid restrictions), comorbidities, and potential for pregnancy. Lastly, all patients placed on ARV therapy should be assessed by the pharmacist for drug interactions in order to prevent potential drug toxicity or decreased efficacy of either ARV or other medications.3 TABLES 6 and 7 provide a list of all ARVs along with their recommended dosing and most common side effects.3,8

tbl5

Prior to initiation of ARV therapy, the following laboratory values should be assessed: a baseline CD4+ count and VL; a basic chemistry panel, including serum creatinine to calculate an estimated creatinine clearance; liver function tests; a CBC with differential; and fasting lipid and glucose levels. A pregnancy test should also be performed prior to starting efavirenz.3 The goal of therapy is to achieve an increase in the CD4+ count by 100 to 150 cells/mm3 in the first year and an undetectable VL by 24 weeks.3

Adverse Effects: Although specific adverse effects are described in TABLES 6 and 7, each class of ARV medications has its own adverse-event risk profile. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are associated with a risk of lactic acidosis, particularly when they are not dose adjusted for renal dysfunction, which is required for all agents in the class except abacavir. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly associated with a risk of rash, while protease inhibitors (PIs) are associated with elevations of both lipids and glucose. Lastly, when using NNRTIs and/or PIs, the patient’s liver function should be monitored closely, particularly if the patient is co-infected with hepatitis.3,8

tbl6

tbl7

Adherence: In order to achieve optimal benefits from any ARV regimen, an adherence rate of at least 95% must be achieved. Factors that contribute to poor adherence include low level of literacy, age-related challenges (such as poor vision), psychosocial issues (depression, dementia), active substance abuse, difficulty taking medications due to size or pill burden, adverse effects, and treatment fatigue. Pharmacists can address many of the factors that contribute to poor adherence and serve as part of a multidisciplinary health care team to improve patient outcomes.3

Selection of ARV therapy in patients who experience drug failure or who are unable to tolerate first-line regimens requires the input of HIV experts. Additionally, these providers may often recommend combinations that do not follow the routine selection of two NRTIs and either a PI or an NNRTI when there is extensive drug resistance. In all cases, the pharmacist should be aware that a minimum of two to three active ARV agents is recommended for the treatment of any patient.

Conclusion

STDs—especially HIV—remain a major public health challenge. Pharmacists should actively work with clinicians in the selection of the most suitable anti-infective agent or ARV regimen for the treatment of STDs and HIV. In addition, pharmacists can monitor and counsel patients regarding their drug therapy in order to achieve optimal outcomes while minimizing side effects and unnecessary toxicity. Pharmacists must actively work with patients and other health care providers to ensure the proper prevention and treatment of STDs.

REFERENCES

  1. CDC. Trends in sexually transmitted diseases in the United States: 2009 national data for gonorrhea, chlamydia, and syphilis. www.cdc.gov/std/stats09/ trends.htm. Accessed March 30, 2011.
  2. Workowski KA, Berman S; CDC. Sexually transmitted diseases treatment guidelines, 2010. MMWR. 2010;59(RR-12):1-110.
  3. Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. January 10, 2011; 1-166. www.aidsinfo.nih.gov/ ContentFiles/AdultandAdolescentGL.pdf. Accessed April 16, 2011.
  4. Knodel L. Sexually transmitted diseases. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw Hill; 2008.
  5. LaFond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev. 2006;19:29-49.
  6. Association of Public Health Laboratories and CDC. Laboratory diagnostic testing for Treponema pallidum. Expert consultation meeting summary report. January 13-15, 2009. Atlanta, GA.www.aphl.org/aphlprograms/infectious/std/Documents/ LaboratoryGuidelinesTreponemapallidumMeetingReport. pdf. Accessed March 30, 2011.
  7. CDC fact sheet: trichomoniasis. www.cdc.gov/std/ trichomonas/STDFact-Trichomoniasis.htm. Accessed March 30, 2011.
  8. Lexi-Comp Online. Hudson, OH: Lexi-Comp, Inc; 2011. www.lexi.com. Accessed April 16, 2011.
  9. CDC fact sheet: gonorrhea. www.cdc.gov/std/ gonorrhea/STDFact-gonorrhea.htm. Accessed March 30, 2011.
  10. CDC fact sheet: chlamydia. www.cdc.gov/std/ chlamydia/STDFact-Chlamydia.htm. Accessed March 30, 2011.
  11. Association of Public Health Laboratories and CDC. Laboratory diagnostic testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert consulta tion meeting summary report. January 1315, 2009. Atlanta, GA. www.aphl.org/aphlprograms/infectious/std/ Documents/CTGCLabGuidelinesMeetingReport.pdf. Accessed March 30, 2011.
  12. CDC fact sheet: genital herpes. www.cdc.gov/ std/herpes/STDFact-Herpes.htm. Accessed March 30, 2011.
  13. Valtrex (valacyclovir) package insert. Research Triangle Park, NC: GlaxoSmithKline; September 2008.
  14. Corey L, Wald A, Patel R, et al. Once-daily vala cyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.
  15. CDC. Human papillomavirus (HPV). Screening. www.cdc.gov/hpv/Screening.html. Accessed March 30, 2011.
  16. CDC. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR. 2010;59:630-632.
  17. Act Against AIDS. www.actagainstaids.org. Accessed April 16, 2011.
  18. CDC. HIV in the United States. www.cdc.gov/ hiv/resources/factsheets/us.htm. Accessed April 18, 2011.
  19. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR. 2006;55(RR-14):1-17.
  20. Ratcliffe L, Thomas S, Beeching NJ, et al. Acute presentations of HIV are still missed in low preva lence areas. Postgrad Med J. 2011;87:170-174.
  21. FDA. Approval of rapid INSTI HIV-1 Antibody Test. December 2, 2010. www.fda.gov/ ForConsumers/ByAudien/USPExams/ForPatientAdvocates/ HIVandAIDSActivities/ucm235483.htm. Accessed April 16, 2011.
  22. Edurant (rilpivirine) package insert. Raritan, NJ: Tibotec Pharmaceuticals; May 2011.

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