HIV Infection and Sexually Transmitted Diseases



aThe addition of ritonavir is used to boost the level of the PI it is given with.


ART, antiretroviral therapy; NRTI, nucleos(t)ide reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; InSTI, integrase strand transfer inhibitor.


Data from Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2012;1-240. Available at: http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf, last accessed 12/6/15.



COMPLICATIONS


Viral Infections


Cytomegalovirus Reactivation



  • CMV reactivation is common in patients with advanced AIDS (CD4 count <100 cells/µL3).
  • Manifestations include viremia with fever and constitutional symptoms, chorioretinitis, esophagitis, gastritis, enterocolitis, pancreatitis, acalculous cholecystitis, bone marrow suppression, necrotizing adrenalitis, and upper and lower respiratory tract infections.
  • End-organ disease is seen most often when CD4 counts are <50 cells/µL3.
  • Ganciclovir 5 mg/kg IV or valganciclovir 900 mg PO every 12 hours is an effective induction therapy for chorioretinitis and gastrointestinal (GI) disease but is associated with significant hematologic toxicity.3 Blood cell counts should be monitored for neutropenia. Concomitant granulocyte colony–stimulating factor can be used as a possible means of ameliorating ganciclovir myelotoxicity.
  • Relapse after drug discontinuation is common, usually necessitating maintenance therapy until CD4 counts are >100 cells/µL3 for 6 months.
  • Patients with retinitis who are intolerant of systemic ganciclovir may benefit from intravitreal administration of the drug by an experienced ophthalmologist.
  • Foscarnet is indicated for ganciclovir-resistant CMV or those failing ganciclovir therapy.

Other Herpesviridae



  • Herpes simplex virus-2 (HSV-2), but not HSV-1, has been identified more commonly in HIV-infected individuals than in HIV-negative individuals.

    • HSV-2 likely facilitates the transmission of HIV by providing a portal of entry (e.g., the genital ulcer) and by increasing HIV viral shedding in the genital tract.
    • HSV-2 coinfection has also been found to speed the progression of HIV to AIDS.
    • HSV infection has been associated with esophagitis, proctitis, pulmonary disease, and large, atypical, persistent cutaneous ulcerations.
    • IV acyclovir is usually effective for these problems, but relapses are frequent and individuals may require chronic HSV suppression.3

  • Varicella-zoster virus may cause typical dermatomal lesions or disseminate. Recurrent disease, meningoencephalitis, and cranial neuritis have been reported. Acyclovir 800 mg PO five times per day or famciclovir 500 mg PO tid is the treatment of choice.
  • Evidence of Epstein-Barr virus (EBV) infection is common in patients with AIDS, particularly oral hairy leukoplakia, a benign condition on the lateral aspect of the tongue.

    • Oral acyclovir may be effective but should be reserved for symptomatic cases.
    • EBV is also associated with central nervous system (CNS) lymphomas in individuals with advanced AIDS (generally CD4 count <50 cells/µL3).
    • Effective therapy for EBV-related malignancies includes ART.

JC Virus



  • JC virus is a polyomavirus that is associated with progressive multifocal leukoencephalopathy (PML).
  • Diagnosis is made by characteristic clinical features, MRI, and polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) for JC virus. Detection of JC virus via PCR is needed for definite diagnosis, but has low sensitivity due to low viremia in the setting of ART.6

    • PML is characterized by subacute (weeks to months) progressive neurologic deficits including altered mental status, visual loss, weakness, and gait abnormalities.
    • MRI is the imaging modality of choice and reveals multifocal white matter hyperintensities on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images.
    • No effective therapy has been identified; however, the course may be significantly altered by immune reconstitution via ART.2

Human Papillomavirus



  • HPV causes a wide spectrum of disease in HIV-infected patients, from transient infection to anogenital warts (HPV types 6 and 11) and squamous cell cancers (HPV types 16 and 18).
  • HIV-infected women have a 5% to 10% increase in cervical intraepithelial neoplasia over HIV-negative women. Risk of more advanced cervical cancer increases with lower CD4 counts.
  • Likewise, anal intraepithelial neoplasia is more common in HIV-infected men.
  • Although usually asymptomatic, cervical, vaginal, or anal lesions may cause pain or spotting.
  • Annual pelvic examinations and cervical Pap smears are recommended in HIV-infected women with referral and additional testing as indicated by abnormal results.
  • The role of anal pap smears in HIV-infected patients, especially MSM, is under investigation.
  • There are now two vaccines available for HPV (bivalent for types 16 and 18 and quadrivalent for types 6, 11, 16, and 18).
  • The efficacy of the HPV vaccine in HIV infection is unknown, but the vaccine appears to be safe and produces a robust immune response.5 It may be reasonable to vaccinate individuals aged 9 to 26 years old, as is recommended for HIV-negative individuals.

Bacterial Infections


Bacterial Pneumonia



  • Bacterial pneumonias occur with increased frequency and are a common cause of morbidity.
  • Pneumonias are usually due to Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae.
  • Pneumonia due to gram-negative enteric organisms occurs in advanced HIV disease.
  • Chest radiographs may reveal typical lobar pneumonia, but diffuse interstitial infiltrates similar to PCP have been reported.

Syphilis



  • The natural history of syphilis may be altered by HIV infection.
  • Reactivation of previously treated disease, active disease with negative serology, asymptomatic neurosyphilis, and relapse after standard therapy have been reported. The optimal management of syphilis in this setting remains unclear.
  • Current guidelines suggest at least annual screening for syphilis in HIV-infected individuals and more frequently in patients with high-risk behavior. Additional information on diagnosis is provided later in this chapter.
  • Lumbar puncture is reserved for seropositive patients with neurologic symptoms. There are also data to support performing lumbar puncture in HIV-infected individuals with a serum rapid plasma reagin (RPR) titer >1:32 or CD4 count <350 cells/µL3.
  • Up to 20% of HIV-infected individuals will remain serofast after successful treatment of syphilis; serum RPR or Venereal Disease Research Laboratory (VDRL) remains reactive at a low titer, generally <1:8. The clinical relevance of this is unclear, but a fourfold rise in titer above this serofast baseline is indicative of reinfection or reactivation and may warrant a lumbar puncture to investigate for neurosyphilis.

Bacterial Diarrhea



  • Bacterial diarrhea due to Salmonella spp., Campylobacter spp., and Shigella spp. is more common in HIV patients, particularly MSM.
  • Nontyphoidal salmonellae (especially Salmonella typhimurium) are associated with invasive disease that often recurs or persists despite appropriate antibiotics.

    • Preferred treatment is ciprofloxacin for 7 to 14 days for diarrhea or 4 to 6 weeks for bacteremia.
    • Initial IV therapy should be followed by long-term oral suppressive therapy based on susceptibility testing; relapse may occur as soon as therapy is discontinued.

  • Campylobacter diarrhea is treated with ciprofloxacin, but resistance is increasing.
  • Shigellosis treatment is with ciprofloxacin or TMP-SMX.

Mycobacterial Infections


Tuberculosis



  • TB can occur at any CD4 count, but extrapulmonary manifestations occur with increased frequency in patients with lower CD4 counts.
  • In the developing world, TB is the most prominent AIDS-defining illness, and in the developed world, TB is most commonly diagnosed in substance abusers, immigrants from high-prevalence countries, and the urban poor.
  • Atypical radiographic patterns and extrapulmonary disease are quite common; apical cavitary disease is uncommon in advanced HIV disease.
  • See Chapter 26 for the treatment of TB.
  • After ruling out active disease, isoniazid for 9 months should be considered in any HIV-infected patient with a reactive (>5-mm induration) TST or positive IGRA. Pyrazinamide plus rifampin for 2 months is an alternative, although there are significant drug interactions with ART and rifampin.

Mycobacterium Avium Complex



  • MAC is one of the most frequent opportunistic pathogens in patients with advanced AIDS (usually CD4 count <50 cells/µL3).
  • Generalized infection and GI disease are the most common manifestations.
  • The organism can be cultured from sputum, blood, bone marrow, and tissue from the GI tract.
  • Treatment with clarithromycin, ethambutol, and rifabutin is often effective.3
  • For patients with CD4 counts <50 cells/µL3, MAC prophylaxis therapy should be initiated with either azithromycin 1,200 mg PO weekly or clarithromycin 500 mg PO bid.

Fungal Infections


Candidiasis



  • Persistent oral, esophageal, and vaginal infections are common; dissemination is rare in the absence of other risk factors such as IV catheters.
  • The severity and frequency of mucocutaneous candidiasis increase with declining immune function.
  • Oral thrush is effectively treated with topical therapy: clotrimazole troches PO five times per day for 14 days.3
  • Frequently recurring thrush can be prevented with fluconazole 100 mg PO daily.
  • Esophagitis should be treated with fluconazole (200 mg one time followed by 100 mg daily for 14 days; higher doses up to 400 mg daily may be required in some patients).
  • Vaginal candidiasis can be treated with antifungal vaginal suppositories as discussed later in this chapter.

Cryptococcosis



  • Cryptococcus neoformans is the most common cause of fungal CNS disease in patients with AIDS.
  • Symptoms may be mild; therefore, the threshold for performing a lumbar puncture should be low.
  • Lumbar puncture results include elevated opening pressure (often >200 mm H2O), lymphocyte predominant pleocytosis, and low glucose. However, normal CSF parameters occur in as many as 25% of AIDS patients with cryptococcal meningitis, so a cryptococcal antigen should be sent for all AIDS patients in whom a lumbar puncture is performed.
  • Repeat lumbar puncture is indicated for clinical deterioration as well as relief of elevated opening pressures, which are associated with poor outcomes.
  • Initial treatment is with IV amphotericin B and flucytosine for 2 weeks, followed by fluconazole 400 mg daily for 8 to 10 weeks.3
  • Following acute treatment, maintenance therapy is required with fluconazole 200 mg daily until CD4 count is >200 cells/µL3.
  • Response is usually monitored clinically and is generally slow.

Histoplasmosis



  • Histoplasma capsulatum is an important pathogen in patients with AIDS from endemic areas and may cause disseminated disease and septicemia. The organism’s endemic areas include the Ohio and Mississippi river valleys in the US, Central and South America, parts of southern Europe, Africa, eastern Asia, and Australia.
  • Diagnosis is made by sending a urine H. capsulatum antigen; the organism can also be cultured from blood and bone marrow.
  • Pancytopenia may result from bone marrow involvement.
  • Treatment includes a 12-week induction phase with a subsequent long-term maintenance phase to complete 1 year of therapy.
  • A cumulative dose of amphotericin B 1.5 to 2.0 g is given initially for severely ill patients. For patients who are intolerant of amphotericin B, liposomal amphotericin B can be considered. Itraconazole is effective for induction in milder disease. Itraconazole is also used for the maintenance phase.3

Coccidioidomycosis



  • Coccidioides spp. infections occur in patients with AIDS from endemic areas (southwestern US and northern Mexico).
  • In immunocompetent hosts, primary infection is a self-limited acute pneumonia known as valley fever.
  • Extensive pulmonary disease with extrapulmonary spread, including meningitis and lymphadenopathy, is common in AIDS patients.
  • Fluconazole 400 mg daily is usual treatment, with amphotericin B as an alternative therapy.3
  • Lifelong maintenance treatment is required for coccidioidal meningitis.

Pneumocystis Pneumonia



  • Pneumocystis jiroveci pneumonia remains the most common opportunistic infection in patients with AIDS and a leading cause of morbidity and mortality.
  • Presenting symptoms include progressive dyspnea, fever, and cough; early disease may have a subtle presentation and a normal chest radiograph.
  • The treatment of choice for PCP is TMP-SMX 5 mg/25 mg/kg PO or IV every 6 to 8 hours for 21 days.3

    • Anemia or rashes can occur in AIDS patients who are treated with TMP-SMX but may not require a change in therapy.8
    • For patients who do not tolerate TMP-SMX, dapsone-trimethoprim, clindamycin-primaquine, and pentamidine are other options.

  • In patients with well-documented PCP and moderate-to-severe disease (arterial oxygen pressure <75 torr on room air), adjunctive use of steroids prevents adult respiratory distress syndrome and leads to a survival benefit.9 Prednisone (or equivalent methylprednisolone) 40 mg PO bid for 5 days, followed by 40 mg PO daily for 5 days, followed by 20 mg PO daily for the duration of antipneumocystis therapy is recommended.

Protozoal Infections


Toxoplasma Reactivation



  • Toxoplasma gondii typically presents in HIV-infected patients with CD4 counts <100 cells/µL3.
  • It is characterized by multiple CNS lesions presenting as encephalitis with headache, confusion, fever, and focal neurologic findings. Extracerebral toxoplasmosis has also been reported.
  • Treatment with sulfadiazine 25 mg/kg PO every 6 hours (or TMP-SMX 5 mg/25 mg/kg PO or IV every 6 to 8 hours) plus pyrimethamine 100 to 150 mg PO on day 1 and then 50 to 75 mg PO daily often results in improvement, but indefinite therapy is needed to prevent relapse.3 Folinic acid 5 to 10 mg PO daily can be added to minimize hematologic toxicity.
  • For patients with sulfonamide allergy, clindamycin 600 mg PO four times per day can be substituted.

Diarrheal Diseases



  • Cryptosporidium spp., Isospora belli, and Cyclospora cayetanensis may all cause severe and prolonged diarrheal illness in patients with AIDS. Isospora belli is most frequently seen in MSM.
  • Diagnosis of cryptosporidiosis is by microscopy, immunoassay, or PCR. Diagnosis of isosporiasis and cyclosporiasis requires acid-fast staining and other specific staining techniques.
  • No therapy has proved to be effective for cryptosporidiosis besides immune reconstitution through ART (CD4 count >100 cells/µL3). TMP-SMX treats isosporiasis and cyclosporiasis.3

Neoplasms



  • Neoplasms associated with AIDS include non-Hodgkin lymphoma and Kaposi sarcoma. Primary CNS lymphomas are common and may be multicentric. The treatment of these conditions is beyond the scope of this manual.
  • As noted above, women should receive annual screening for cervical cancer. In addition, there is growing literature on the need for anal screening in both men and women.

Metabolic Complications


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Nov 3, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on HIV Infection and Sexually Transmitted Diseases

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