Segundo Ciclo de Reflexión: Construyendo Nuevas Experiencias

limited countries, IRIS increasingly is being recognized in patients receiving ART. Clinicians should include IRIS in the differential diagnosis when evaluating patients who recently have begun ART and present with new or worsening symptoms of an OI. However, limited diagnostic testing resources may make it difficult to establish IRIS and other diagnoses.

Given that coinfection with HIV and TB is epidemic in many countries, and because IRIS is not uncommon in patients with TB, clinicians should be particularly vigilant about symptoms that may signal IRIS. As in resource-sufficient countries, consultation with a clinician trained in caring for patients with HIV is recommended if diagnosis or treatment is in question.

Patient Education

• Patients starting ART who have CD4 counts of <100 cells/µL or known concomitant OIs should be counseled about the likelihood of IRIS.

• All patients starting ART should be advised to contact the clinic promptly if they experience new or worsening symptoms. • Advise patients to take their medications for

HIV and for the treatment or prevention of OIs exactly as prescribed.

References

• Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706.

• Havlir DV, Kendall MA, Ive P, et al.; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91.

• Blanc FX, Sok T, Laureillard D, et al.; CAMELIA (ANRS 1295–CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1471-81.

• DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000 Sep 19;133(6):447-54.

• French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009 Jan 1;48(1):101-7.

• Jacobson MA. Clinical Implications of Immune Reconstitution in AIDS. In: Coffey S, Volberding PA, eds. HIV InSite Knowledge Base [textbook online]. San Francisco: UCSF Center for HIV Information; 2006. Available at hivinsite. ucsf.edu/InSite?page=kb-03-04-03. Accessed December 1, 2013.

• Lawn SD, Wilkinson RJ, Lipman MC, et al. Immune reconstitution and “unmasking” of tuberculosis during antiretroviral therapy. Am J Respir Crit Care Med. 2008 Apr 1;177(7):680-5.

• Manosuthi W, Van Tieu H, Mankatitham W, et al.; N2R Study Team. Clinical case definition and manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2009 Nov 27;23(18):2467-71.

Sec tion 6: C omor bidities , Coinf ec tions , and C omplications

• Meintjes G, Lawn SD, Scano F, et al.; International Network for the Study of HIV-associated IRIS. Tuberculosis-associated immune reconstitution inflammatory

syndrome: case definitions for use in resource- limited settings. Lancet Infect Dis. 2008 Aug;8(8):516-23.

• Meintjes G, Rabie H, Wilkinson RJ, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome and unmasking of tuberculosis by

antiretroviral therapy. Clin Chest Med. 2009 Dec;30(4):797-810.

• Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at aidsinfo.nih.gov/guidelines. Accessed December 1, 2013.

• Ratnam I, Chiu C, Kandala NB, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis. 2006 Feb 1;42(3):418-27.

• Shelburne SA, Montes M, Hamill RJ. Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother. 2006 Feb;57(2):167-70.

• Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005 Mar 4;19(4):399-406.

• Shelburne SA 3rd, Darcourt J, White AC, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005 Apr 1;40(7):1049-52. • Zolopa A, Andersen J, Powderly W, et al.

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575.

Anal Dysplasia | 383 Sec tion 6: C omor bidities , Coinf ec tions , and C omplications

Anal Dysplasia

Background

Anal cancer is a squamous cell cancer associated with human papillomavirus (HPV), the same virus that is associated with cervical cancer (see chapter Cervical Dysplasia). The anal canal and cervical canal share a common embryologic origin: both have a squamocolumnar transition zone and are prone to infection with HPV, a sexually transmitted virus. HPV infection, in combination with cofactors, may stimulate dysplastic changes in the cervix or anus that may develop through precursor stages into squamous cell cancer. In the United States, the incidence of anal cancer in the general population is approximately 1:100,000 per year. In HIV-infected men and women, the incidence of anal cancer and the prevalence of its precursors are significantly higher than in the general population. Advanced immunosuppression, as demonstrated by lower CD4 cell counts, appears to increase the risk of anal intraepithelial neoplasia (AIN), a precursor to cancer, and anal cancer. Rates of anal cancer also are higher among men who have sex with men (MSM), whether HIV infected or uninfected, compared with the general population. Current rates in an HIV-infected MSM population have been estimated to be as high as 70-144 per 100,000. Although most studies have examined anal dysplasia and cancer in MSM, its prevalence also is high among HIV-infected women and heterosexual men. Some studies of HIV-infected individuals have shown that anal HPV infection is present in 93% of MSM and 76% of women, and that anal dysplasia (any grade) is present in 56% of MSM and 26% of women. In some studies of HIV-infected women, anal dysplasia has been seen more frequently than cervical dysplasia, and it has not been exclusive to those with behavioral risk factors (e.g., history of receptive anal intercourse). HIV-infected heterosexual men with no history of receptive anal intercourse also have elevated risks of anal HPV infection. Thus, although receptive anal intercourse may increase the likelihood of anal HPV infection, it is not a prerequisite for anal HPV or dysplasia.

Screening strategies for anal dysplasia and cancer and the optimal management of abnormal test results are areas in which questions remain unanswered. The rationale for screening for anal cancer and its precursors is based on the success of cervical Papanicolaou (Pap) screening in reducing cervical cancer incidence and mortality. Because of the similarities between cervical and anal dysplasia, many experts postulate that many of the paradigms of managing cervical cytologic abnormalities may be translated to management of anal dysplasia. However, there are no randomized clinical trials that document the value of screening for anal precancers.

Current guidelines from the HIV Medicine Association of the Infectious Diseases Society of America recommend anal pap tests for MSM, women with a history of abnormal cervical Pap tests or a history of anal receptive sex, and all HIV-infected persons with genital warts, though they do not specify screening intervals. The New York State Department of Health AIDS Institute recommends that an anal Pap test be done at baseline and annually thereafter for MSM, patients with a history of anogenital warts, and women with abnormal cervical or vulvar histology, and many HIV clinics elsewhere do routine screening. Further investigations are ongoing to define appropriate screening intervals, diagnostic approaches, indications for therapy, and modalities of treatment.

ART and subsequent immune reconstitution does not appear to alter the prevalence or distribution of anal cancers and anorectal disease nor does it appear to reduce the progression of AIN and other cancer precursors.

Sec tion 6: C omor bidities , Coinf ec tions , and C omplications

S: Subjective

Patients with anal dysplasia usually are asymptomatic, and the condition cannot be identified without screening tests. Exophytic anal condylomata may cause itching, discomfort, or bleeding, but are usually associated with low-risk phenotypes of HPV and low-grade dysplasia (note, however, that oncogenic HPV types also may be present). Anal cancer may cause nonspecific symptoms such as pain (with defecation or after

intercourse), itching, bleeding, or sensation of a rectal mass.

Risk factors for anal dysplasia and cancers include the following:

• HIV infection

• CD4 count of <200 cells/µL • RAI

• HPV infection

• Genital warts (or history of genital warts) • Immunosuppression

• High-grade cervical or vulvar dysplasia • Cigarette smoking

• Multiple sex partners

Ask patients about these risk factors, about previous history of anal dysplasia or cancer, and about previous screening.

O: Objective

Examine the genital and perianal region, and perform a digital anorectal examination. Look and feel for masses, condylomata, and other abnormalities such as hypo- or hyperpigmented plaques or lesions, and lesions that bleed. Note that simple visual examination may not reveal abnormalities. In women, also examine the vulva, vagina, and cervix. Examine the inguinal lymph nodes.

If the digital examination is performed in conjunction with an anal Pap test, the Pap specimen should be obtained before the

introduction of lubrication.

Anoscopic examination with the naked eye may not reveal any abnormality because dysplastic tissue tends to be flat and difficult to differentiate from normal anal tissue; application of 3% acetic acid is required (see below for a description of how high-resolution anoscopy [HRA] is performed).

A: Assessment

HIV-infected individuals with anal dysplasia have an increased risk of progression to anal cancer. If the history or physical examination reveals abnormalities suggestive of anal dysplasia or anal cancer, an appropriate evaluation should be undertaken. Because most patients with anal dysplasia have no symptoms, anal cancer screening using a Pap test can be considered if follow-up evaluation of an abnormal cytologic result (ASCUS or higher, see Bethesda 2001 grading system, below) by high-resolution anoscopy is available either on-site or by referral.

P: Plan