Therapeutics/Consequences of Human Immunodeficiency Virus Infection

Case

A 26-year-old gay male was diagnosed with Human Immunodeficiency Virus infection 5 years ago. His CD4 nadir was 140cells/mm³ 2 years after diagnosis, but he has been on antiretroviral therapy for 3 years with excellent adherence (last CD4 = 480cells/mm³ and Human Immunodeficiency Virus RNA undetectable). In addition to Human Immunodeficiency Virus infection, he has a history of syphilis (adequately treated with appropriate rapid plasma reagin (RPR) response), gonorrhea on two occasions (oral and rectal), and past hepatitis A and B. His glycoprotein G herpes simplex-2 serology was negative. He is otherwise healthy.

Despite multiple prevention interventions by physicians and social workers, he continues to episodically have unprotected, receptive oral and anal intercourse. He attends clinic complaining of painful, blood-tinged bowel movements for 5 days associated with a low-grade fever and malaise. He denies recent travel, foreign body exposure, animal contact, or similar prior symptoms. On general physical examination the only abnormalities were mild perianal ulcerations and several tender inguinal lymph nodes; on anoscopy, there were diffuse, painful, and shallow ulcerations with overlying bloody exudates throughout the visualized anorectal field. The following studies were ordered: darkfield examination, syphilis serology, gonococcal and chlamydial DNA probes, viral culture (primarily for herpes simplex viruses in light of his good immune status), repeat glycoprotein G herpes simplex serology, Clostridium difficile toxin assay, and routine stool culture.

Within 24h his herpes simplex virus-2 culture was positive; all other studies were negative including herpes simplex virus-2 serology. The patient was treated with valacyclovir 1 g three times per day for 10 days then placed on 500mg twice per day for prophylaxis of anogenital herpes. Follow-up serologies 8 weeks later demonstrated glycoprotein G herpes simplex virus-2 seroconversion — thus, the patient had primary herpes simplex virus-2 anoproctitis.

Therapeutics

Therapeutic management for all causes of diarrhea should include appropriate fluid and electrolyte replacement. Symptomatic therapy with antidiarrheal agents such as bismuth subsalicylate and loperamide may be used to decrease the number of stools passed per day. However, caution should be observed with the use of antimotility drugs in the treatment of invasive forms of diarrhea as the development of toxic megacolon may occur. Appropriate antimicrobial therapy is generally pathogen-specific. However, if empiric therapy is necessary, ciprofloxacin 500 mg orally twice daily for 3-5 days is appropriate for adults with febrile dysenteric diarrhea.

For the empiric therapy of persistent diarrhea (>14 days’ duration), metronidazole 250mg orally three times daily for 7 days may be administered to adults. For opportunistic infections due to Cytomegalovirus, Mycobacterium avium complex, Cryptosporidium and microsporidia, combination antiretroviral therapy should be included in the treatment regimen. Appropriate immune reconstitution is often necessary for the cure of disease caused by these pathogens.

Table Causes of enterocolitis and proctitis in Human Immunodeficiency Virus-infected individuals

For the empiric treatment of proctitis, ceftriaxone 125 mg IM once, plus doxycycline 100 mg orally twice daily for 7 days may be used. Fluoroquinolones should not be used in the treatment of gonococcal disease or suspected gonococcal disease due to the high rate of fluoroquinolone resistance.

Summary

Human Immunodeficiency Virus-infected individuals can develop gastrointestinal disorders throughout the course of Human Immunodeficiency Virus infection. Recent studies have demonstrated that Human Immunodeficiency Virus infection involves the gastrointestinal tract (including the colon and rectum) from early infection with depletion of gut-associated lymphoid tissue, throughout chronic infection (when gut-associated lymphoid tissue may not be fully restored even with adequate antiretroviral therapy), and into full-blown acquired immunodeficiency syndrome.

Human Immunodeficiency Virus itself can result in a unique enteropathy The associated progressive immunodeficiency which occurs in untreated Human Immunodeficiency Virus-infected patients can allow fulminant reactivation of usually benign, latent infections (e.g., cytomegalovirus colitis or chronic, severe perirectal herpes simplex type 2 (herpes simplex virus-2) infection) or the transformation of a ubiquitous pathogen into a malignant, invasive agent (e.g., Mycobacterium avium complex). Many sexually-transmitted infections may be more severe and more varied in presentation in Human Immunodeficiency Virus-infected patients, and their therapy may be more complex. These patients are also at increased risk for certain malignancies of the colon (especially Kaposi sarcoma) and rectum (human papillovirus-associated intraepithelial neoplasia).

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Jennifer Bowles

Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.