An unusual outbreak of Kaposi sarcoma (KS) and Pneumocystis carinii pneumonia among young homosexual men was first reported by the Centers for Disease Control and Prevention (CDC) in 1981. By the end of 1982, the term acquired immune deficiency syndrome (AIDS) was born. In 1983, two research groups published their findings of the retrovirus thought to be responsible for AIDS. Initially referred to as human T-lymphotrophic virus III and lymphadenopathy-associated virus, it turned out both researchers were dealing with the same virus, renamed human immunodeficiency virus (HIV) in 1986.
AIDS and HIV are global pandemics. By the end of 2011, the World Health Organization estimated that 34 million people were living with HIV. This number varies from country to country, with African nations being the most severely affected; 4.9% of the African population is living with HIV. More than 2.5 million new cases of HIV were diagnosed in 2011, and the World Health Organization estimates that 1.7 million people worldwide succumbed to AIDS-related illnesses in 2011. Heterosexual spread is the most common mode of transmission, although in the Western world, homosexual men are still the most frequently affected.
HIV infections and the syndrome of AIDS are big public health problems in the United States. The CDC estimated that in the United States in 2010 there were 47,500 new HIV infections and that 872,990 people were living with HIV. The CDC also reported that in the United States in 2010, a total of 32,052 people were diagnosed with AIDS and 487,692 people were living with AIDS. The number of AIDS-related deaths in the United States in 2010 was 15,529, and the estimated total AIDS-related deaths through 2010 was more than 636,048. Gay and bisexual persons and men who have sex with men are the most frequently affected individuals in the United States. White men having sex with men account for 11,200 of the new infections, followed by black men having sex with men at 10,600.
HIV is spread through exposure to infected blood (transfusions, needle sticks, or needle sharing), sexual contact (including oral, vaginal, and anal sex), and transmission from pregnant mothers to fetuses. The risk varies depending on the type of exposure and the surrounding circumstances. Direct exposures to infected blood or needle sticks still carry the highest risk. Varying sexual acts carry differing risks of infection, with receptive anal intercourse having the highest risk. The rectum is a well vascularized organ with fragile mucosa, allowing for easier transmission of the virus. Multiple publications have shown that the presence of other sexually transmitted diseases increases the risk of HIV transmission.
Primary HIV infection often presents with a short flu-like illness that lasts around 14 days. This illness is accompanied by fever, malaise, and lymphadenopathy. Seroconversion, the period when antibodies are produced by the body’s immune system, occurs in 4 to 10 weeks in most patients but can take up to 6 months. In this “window” period, antibody tests may give false-negative responses. Rapid antibody tests are available and used for point of care tests to aid in the diagnosis of HIV infection. The Food and Drug Administration has recently approved the use of a rapid in-home test for this purpose. Further testing is required to confirm the diagnosis, and a negative result may not be reliable in the “window” period. The enzyme-linked immunosorbent assay tests the patient’s serum against a plate of HIV antigens. If antibodies are present, the test is confirmed via Western blot. The current immunoassay for detection of HIV is in its fourth generation. It uses a synthetic peptide or recombinant protein antigens that are designed to detect immunoglobulin (Ig)M and IgG antibodies and p24 antigen. A positive result is tested to differentiate HIV-1 antibodies from HIV-2 antibodies. Patients with a positive result from this second test should be considered positive to either HIV-1 or HIV-2 and should seek medical care for further testing for viral load and resistance assays.
The introduction of antiretroviral therapy, more commonly referred to as highly active antiretroviral therapy (HAART), has helped improve the outcomes of patients infected with HIV. HAART medication is made up of three categories of drugs: protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and nucleoside reverse transcriptase inhibitors. The combination of these drugs has allowed patients to live longer, increasing life expectancy from months to decades. A recent study from the HIV Prevention Trials Network confirmed that HAART therapy can reduce the risk of sexual transmission of HIV from one partner who is infected with HIV to his or her noninfected partner by 96%.
Cytomegalovirus (CMV) is a double-stranded DNA virus first isolated in 1956. It is a member of the herpes virus family, often establishing a latent infection after the initial exposure. Recent statistics suggest that at least 60% of the U.S. population has been exposed to CMV. CMV infection is thought to occur most frequently in immunosuppressed patients. The risk of exposure increases with the age of the patient and varies according to geographic location. CMV, the most common colonic infection in patients with HIV, is found in up to 10% of cases. Clinical disease often occurs when the CD4 counts have fallen below 100 cells/mm 3 . Prior to the introduction of HAART medication, the incidence of CMV end organ dysfunction was greater than 20% per year among patients with HIV and AIDS. According to reports from recent AIDS literature, the proportion is now 3.2% to 5% per year.
The role of CMV in the development of colitis remains unclear. The question is whether the virus itself is the source or acts as a promoter or cofactor for other infections. Infection often produces a vasculitis affecting the capillaries and arterioles, leading to thrombosis and subsequent ischemia, thrombosis, or ulceration. One study of the mechanism of CMV colitis suggested that the CMV virus helped block the macrophage inhibition of the HIV-1 infection, enhancing inflammation and tumor necrosis factor-α release.
The most common symptoms of CMV colitis are bloody diarrhea and abdominal pain. Patients may present with hemorrhage but also can have fever, weight loss, and anorexia. Diarrhea is a symptom of other opportunistic infections in the AIDS population, such as cryptosporidium, Giardia, and shigella. Stool cultures are important. Perianal ulceration may occur and must be distinguished from herpes simplex.
Patients presenting with suggestive symptoms will often undergo extensive workup including radiographs, computed tomography scan, and colonoscopy. The computed tomography findings may include colonic wall thickening, localized edema, and fat stranding. These findings are suggestive of colitis, but the diagnosis cannot be confirmed without endoscopic evaluation. A barium enema was often performed in the past, with findings including diffuse mucosal ulceration, skip areas, and thumbprinting.
The gold standard for diagnosis for CMV colitis is colonoscopy with biopsy. Endoscopic findings include submucosal hemorrhage and diffuse ulcerations that measure 3 to 5 mm. Random biopsies are recommended to distinguish CMV from other causes of colitis. The ulcers may be seen throughout the colon but can also be patchy, commonly clustering in the right colon. In one study, in 13% of patients, disease was only found in the right colon. For that reason, a full colonoscopy rather than a flexible sigmoidoscopy is important. CMV lesions can resemble those of ulcerative colitis and occasionally have findings of a whitish membrane similar to pseudomembranous colitis.
Diagnosis of CMV colitis is confirmed via biopsy. The pathognomonic finding on histology, often described as “owl eyes,” is the presence of large basophilic intranuclear cytomegalic viral inclusion bodies. As the cells infected with the virus necrose, the inclusion bodies become less clear and take on a blue-red appearance, which is highly suggestive of CMV colitis. CMV can be detected by antigen pp65 testing and polymerase chain reaction assays. However, viremia may be present in the absence of colitis, suggesting latent infection. Treatment of patients with CMV but without evidence of colitis is not recommended. Treatment should start with the initiation of HAART therapy by HIV specialists.
The treatment of choice for CMV colitis is ganciclovir, and improvement is often seen in the first week. Ganciclovir is a competitive inhibitor of deoxyguanosine triphosphate incorporation into DNA. Treatment dose is 5 mg/kg by intravenous (IV) administration every 12 hours for 14 to 21 days. Adverse effects include neutropenia, anemia, thrombocytopenia, fever, diarrhea, and liver dysfunction.
In pre-HAART studies, maintenance therapy was frequently required for patients with evidence of CMV colitis. This maintenance therapy was often given as an oral preparation of valganciclovir or an IV maintenance dose of ganciclovir every 4 to 6 weeks. More recent studies from the National Institutes of Health challenge those recommendations. Current literature does not support the use of lifelong maintenance therapy, although it should be considered if relapse occurs.
Foscarnet is a DNA chain inhibitor of phosphorylation that is active against herpes simplex virus and CMV virus. It is often used against ganciclovir-resistant strains of the CMV virus. Foscarnet is given at a dose of 90 mg/kg by IV administration every 12 hours for 14 to 21 days. Foscarnet is nephrotoxic, so the patient must stay well hydrated during treatment to avoid renal impairment. Adverse effects include anemia, headache, nausea, and neurologic toxicities.
Other drugs, including oral valganciclovir, can be used when symptoms are less severe. No evidence exists that preemptive therapy with antiviremic medications is necessary in high-risk patients. CMV disease is best prevented by utilization of HAART to keep CD4 counts above 100 cells/mm 3 . The treatment of CMV retinitis includes newer medications such as cidofovir that have not been adopted for the treatment of CMV colitis. Since the advent of HAART in 1996, the incidence of opportunistic infections, including CMV, has significantly decreased.