Prevention of Opportunistic Infections (OI) in Patients With HIV Infection 

Updated: Apr 11, 2019
  • Author: David R Haburchak, MD, FACP; Chief Editor: John Bartlett, MD  more...
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General Guidelines for Prophylaxis

Prevention of opportunistic infections in patients with HIV disease is important to optimize outcome. All HIV-related infections and malignancies escalate in frequency and morbidity as the absolute CD4 T-lymphocyte count falls toward 200 cells/μL and below. Therefore, the CD4 count must be known to determine the risk of infection in a specific patient and serve as an impetus to drug prophylaxis or other interventions. Patients should be aware of their CD4 count and their risk of specific infections. For patients who are stable on antiretroviral therapy (ART) with a CD4 count above 200 cells/μL, CD4 monitoring is considered unnecessary by some experts. [1]

All HIV-infected individuals are susceptible to a wide array of opportunistic infections and are at higher risk to pathogenic organisms that plague the general population. Behaviors and the social environment of HIV-positive patients may place them at higher risk of venereal, skin, pulmonary, gastrointestinal, and liver infections than the general population, as well as infectious-related malignancies such as lymphoma, cervical, anal, and liver cancer.

Besides causing morbidity and mortality by themselves, opportunistic infections accelerate the progression of HIV disease itself, especially syphilis and tuberculosis (TB), while ulcerative lesions can facilitate spread of HIV. [2] For this reason, current guidelines emphasize concurrent antiretroviral therapy (ART) with prophylaxis, treatment, secondary prophylaxis, or continuation therapy of opportunistic infections. Timing of ART warrants thoughtful consideration and knowledge of particular immunological, psychosocial, and economic considerations in the specific patient.

Because many HIV-seropositive patients first present late after infection, early identification of CD4 cell count and initiation of appropriate prophylaxis remains critically important. Academic detailing by pharmacists was shown in a North Carolina hospital to increase the use of early prophylaxis in newly diagnosed HIV inpatients. [3] Many patients with newly diagnosed HIV continue to present with opportunistic infections or develop them within 180 days of enrollment. [4] Nevertheless, it is very encouraging that the rates of opportunistic infections and mortality among HIV cohorts have decreased by 60% over the past two decades. [5] Particularly noteworthy has been the decline in mortality associated with Pneumocystis infection in the United States. [6] Tuberculosis, cryptococcal meningitis, and pneumococcal pneumonia continue to be major causes of mortality in patients with HIV infection and are the focus of much investigation [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17] and updated WHO guidelines [18] .

Guidelines from the US Centers for Disease Control and Prevention, National Institutes of Health, and the Infectious Diseases Society of America (CDC/NIH/IDSA) emphasize early HIV detection and the supervised use of ART to maintain cellular immunity before reaching risky CD4 levels. Additionally, early effective HIV viral suppression is recommended to possibly decrease the rate of HIV transmission to others. [2]

The recommendations below use evidence-based criteria as published by the CDC/NIH/IDSA that summarize the strength of the recommendation and quality of the evidence as of March 2019: [2]

Strength of recommendation is as follows:

  • A: Strong recommendation for the statement
  • B: Moderate recommendation for the statement
  • C: Optional recommendation for the statement

Quality of evidence for the recommendation is as follows:

  • I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints
  • II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes
  • III: Expert opinion

Exposure Avoidance

Recommending exposure avoidance is always appropriate, but usually difficult to implement except in the most compulsive patients. Nevertheless, persons infected with HIV should practice appropriate hygiene and dietary precautions, such as avoiding the following: [2, 19]

  • Cat litter and excreta or saliva of farm animals, wild animals, and pets
  • Animal bites and scratches
  • Persons with skin infections
  • Raw meats, eggs, and shellfish; unwashed raw fruits and vegetables
  • Unpasteurized dairy products
  • Drinking untreated lake or river water
  • Human fecal-oral contact

HIV-infected individuals should also limit occupational or recreational exposure to dirt as much as possible in geographical locales with hyperendemic fungal disease (eg, histoplasmosis, coccidioidomycosis, Penicillium marneffei infection). [2]

Specially treated water is not helpful. [2]

Use of male latex condoms is strongly recommended for preventing transmission of HPV and other sexually transmitted diseases. In situations in which male latex condoms cannot be used properly, an FC1 or FC2 Female Condom should be considered for heterosexual vaginal intercourse (AII recommendation) or male same-sex anal intercourse (BIII recommendation). [2]

Drug, alcohol, and tobacco abuse prevention and therapy should be part of any HIV disease management program. Many patients with HIV infection have suffered trauma, placing them at higher risk for poor adherence to preventive and therapeutic interventions. All programs should incorporate principles of trauma-informed care in optimally assisting patients to better health. [20, 21]


Initiation of Prophylaxis and Treatment

Despite increasingly widespread HIV screening, many HIV infections continue to be diagnosed late and after opportunistic infections have already developed. [4] Such patients usually have very low CD4 counts and need prompt treatment and secondary prophylaxis for the presenting opportunistic infection, as well as additional CD4 count–appropriate primary prophylaxis.

In most instances, such preventive therapy is applied prior to the initiation of antiretroviral therapy (ART). Many of these patients have significant psychiatric, social, and economic problems, as well as major medical comorbidities and drug abuse. The healthcare team must address and control these issues if prophylaxis is to be successful; this requires motivation and cooperation on the part of the patient.

Clinicians should withhold ART from asymptomatic patients until the patient has demonstrated mastery of the prophylactic regimen or directly observed therapy can be assured. Exceptions include cases in which renal, hematologic, or neurologic disease is directly attributed to HIV viremia.

Clinicians must weigh the complexity of pill burden, risk of toxicity, and the benefits of co-initiation of ART for patients first presenting with opportunistic infection and Kaposi sarcoma at the time of presentation. Early ART (preferably at the same time as opportunistic infection treatment) is indicated for patients presenting with Pneumocystis carinii pneumonia (PCP), toxoplasmosis encephalitis, and pulmonary tuberculosis. The most recent NIH guideline has rescinded a two-week waiting period for ART in patients presenting with disseminated Mycobacterium avium complex (MAC) infection. Such patients should receive at least two-drug antimycobacterial therapy at the same time and should be monitored closely for symptoms of the immune reconstitution inflammatory syndrome (IRIS). Severe IRIS has also been reported after early ART in the management of cryptococcal and tuberculous meningitis, and it has been suggested that such patients delay ART until at least two weeks of treatment of the opportunistic infection. Patients with CD4 counts of less than 50 cells/μL at presentation should be considered for cryptococcal antigen testing, and, among those diagnosed with cryptococcal meningitis, initial ART should be delayed at least 2 weeks into cryptococcal therapy. [2]

The following CD4 counts are useful landmarks for initiation of antimicrobial prophylaxis:

  • Less than 250 cells/μL - Coccidioidomycosis prophylaxis if seropositive in high-risk area
  • Less than 200 cells/μL - PCP prophylaxis
  • Less than 150 cells/μL - Histoplasmosis prophylaxis if high-risk exposure
  • Less than 100 cells/μL - Toxoplasmosis prophylaxis (if seropositive)
  • Less than 100 cells/uL - Cryptococcosis preemptive therapy if antigen-positive [18]
  • Less than 100 cells/μL - Penicilliosis prophylaxis if living in high-risk area
  • Less than 50 cells/μL - MAC infection prophylaxis unless ART is immediately initiated [2]

Risks of Prophylaxis

Prior to initiation of prophylaxis, the clinician should attempt to clinically exclude active disease, as the prophylactic regimen may not suffice in aborting uncontrolled infection or may even mask signs of infection. In most cases, obtaining a thorough history and conducting an examination with symptom-targeted laboratory and radiologic tests are enough to exclude active P carinii pneumonia (PCP), M avium complex (MAC) infection, and tuberculosis. Increasingly, serum cryptococcal antigen testing is used to screen at-risk patients for early disease, particularly in Africa. [12, 13, 18]

Adverse drug reactions to prophylactic therapy are common and should be expected. Patients should completely understand the purpose of the prophylaxis, the possible adverse effects, and what to do if they occur. Typical toxicities include the following:

  • Trimethoprim-sulfamethoxazole - Rash and neutropenia
  • Dapsone - Rash; anemia; methemoglobinemia, especially if G-6-PD deficient
  • Azithromycin and clarithromycin - Gastrointestinal distress (pain and diarrhea), QT prolongation (clarithromycin)
  • Pyrimethamine - Leukopenia
  • Itraconazole - Hepatitis (hepatitis is less likely with fluconazole), QT prolongation
  • Atovaquone - Headache, nausea, diarrhea, rash, transaminase elevation

As patients live longer with long-term immunosuppression and control of the HIV virus, they often accumulate multiple comorbid conditions associated with early aging. These include renal and hepatic disease, hyperlipidemia, lung disease, and cardiovascular disease. Drug-drug interactions with antiretroviral therapy and prophylactic drugs is inevitable. Automated drug screens used by pharmacies often alert the physician to unanticipated potential interactions of variable significance. Finding one's way through the maze of therapy benefits from the assistance of a pharmacy HIV specialist, especially in moderate to large clinics.


Initial Tests and Prophylactic Regimens

On the patient's first visit, serologies for syphilis; hepatitis A, B, and C; and toxoplasmosis should be obtained. Although the incidence of CMV disease, including retinopathy, has declined significantly, [22] it is recommended that HIV-positive patients who are not at high risk of CMV infection (ie, men who have sex with men, people who intravenously inject drugs, or patients who are exposed to children in daycare centers) be screened to confirm that they are CMV-negative (BIII recommendation). Such HIV-positive, CMV-negative persons would be instructed to limit exposure to CMV by using latex condoms and other barrier precaution (AII recommendation) and be informed of the risk of acquisition in daycare facilities (BII recommendation) and to accept only CMV-seronegative or leukocyte-reduced blood products in nonemergent situations (BIII recommendation). [2]

Urine chlamydial and gonorrheal nucleic acid amplification testing should be performed in all patients with newly diagnosed HIV infection. Similarly, patients who participate in oral or anal receptive intercourse should undergo chlamydial and gonorrheal nucleic acid amplification testing. Women should be evaluated for trichomoniasis. A purified-protein derivative (PPD) skin test should be placed unless a prior positive result for tuberculosis has been documented. An interferon-gamma release assay may be sufficiently sensitive for one-step testing, but false-negative test results are common in advanced immunodeficiency. [2]

Pneumococcal PCV13 vaccine should be administered on the first visit, and on subsequent visits, vaccines for hepatitis A, hepatitis B, diphtheria-tetanus, and influenza should be administered as indicated by serology results, history, and season, respectively. Patients should be given the PPV23 vaccine at least 8 weeks after the PCV13, if it has not already been administered. The 9-valent recombinant HPV vaccine should be given to all patients aged 13-26 years. All live vaccines should be avoided in HIV-infected patients, with the exception of measles and varicella vaccines in immunocompetent patients (in general, CD4 count >200 cells/μL). The meningococcal ACWY vaccine should be administered, but meningococcal B and Haemophilus influenzae B should be administered only under epidemic conditions for hematological disorders, respectively. [2] (For general information on vaccines, see the Medscape Vaccines Resource Center.)


Monitoring Patient Compliance

Once initiated, prophylaxis should be accompanied by education from a trained educator and such teaching documented. The same educator should reinforce later antiretroviral therapy (ART). At each visit, patients should bring their prescription bottles and explain their purpose. Failure to give correct answers or to bring bottles warrants a return visit to the educator. Isoniazid preventive therapy for latent tuberculosis or tuberculosis exposure is particularly important and facilitated by excellent communication with healthcare workers. [9] Reminders delivered via text messaging are increasingly being used to enhance patient adherence.

As patients improve and CD4 counts rise, prophylaxis can often be terminated. The containers of terminated drugs may need to be removed from patients’ possession, and repeated calls and email messages may need to be sent to the pharmacy to ensure cessation of delivery of the drugs to the patient. Continuing unnecessary medication could be a significant problem, especially with computerized prescribing, unless specific efforts are made to stop the drug.


Clinical Landmarks for Terminating Primary Prophylaxis

After retroviral therapy is initiated and HIV viremia suppressed, P carinii pneumonia (PCP) and toxoplasmosis prophylaxis should be continued until the CD4 count exceeds 200 cells/μL for 3 months (AI recommendation) or 100-200 cells/uL with negative HIV viral load for 6 months (BII recommendation). Histoplasmosis prophylaxis can be discontinued when the CD4 count has exceeded 150 cells/μL for 6 months (BIII recommendation), coccidioidomycosis prophylaxis when CD4 counts exceed 250 cells/μL for 6 months (CIII recommendation), and penicilliosis prophylaxis when CD4 counts exceed 100 cells/μL for 6 months (BII recommendation). [2]


Primary Prophylaxis as the Standard of Care

P carinii pneumonia (PCP)

Indications for prophylaxis include a CD4 cell count of fewer than 200 cells/μL (AI recommendation) or < 14% of lymphocytes (BII recommendation). The preferred regimen is trimethoprim-sulfamethoxazole 1 double-strength tablet orally daily or 1 double-strength tablet orally 3 times weekly. Alternatives include dapsone 100 mg orally daily (however, see toxoplasmosis), aerosolized pentamidine 300 mg administered via the Respirgard II nebulizer monthly, or atovaquone suspension 750 mg (5 mL) orally twice daily. [2]

Latent Mycobacterium tuberculosis infection (LTBI) and exposure

Screening for tuberculosis in the HIV-infected population has been suboptimal, with only 47-65% of patients completing screening. The most common predisposition for tuberculosis now is birth or residence outside of the United States. [2]

A course of prophylaxis (LTBI treatment) is indicated for all patients with a history of a positive tuberculin skin test result of 5 mm or greater or a US Food and Drug Administration (FDA)–approved interferon-gamma release assay who have not previously received such therapy (AI recommendation). HIV patients who are close contacts of a person with infectious tuberculosis, yet show no signs themselves of active tuberculosis, should be administered LTBI treatment regardless of screening results (AII recommendation). [2] This appears particularly critical for HIV-seropositive children not on ART, as a Cochrane review of a South African study has shown a 69% reduction in the risk of active tuberculosis and 54% reduction in death. [8] An Ethiopian study showed improved outcomes in adults on combined ART and LTBI therapy. [10]

Active tuberculosis should be excluded by lack of symptoms and negative chest radiograph before prophylactic regimens are started. Active tuberculosis may be more likely in a patient with previous active tuberculosis (treated or untreated) than in a patient without a history of tuberculosis.

Regimens depend on the likelihood that the patient is infected with resistant tuberculous bacilli. The preferred regimen for probable infection with latent isoniazid-sensitive bacilli is isoniazid 300 mg plus pyridoxine 25 mg orally daily for 9 months (AII recommendation).

Patients with suspected isoniazid-resistant infection should receive prophylaxis with rifampin 600 mg daily for 4 months or rifabutin dose adjusted based on concomitant antiretroviral therapy (ART) used (BIII recommendation).

In patients with multidrug-resistant (MDR) tuberculosis or extensively drug-resistant (XDR) tuberculosis, public health authorities should be consulted for recommended regimens and supervision (AII recommendation). [2]

LTBI therapy and ART act independently to decrease the risk of active tuberculosis. Therefore, both should be used, but rifamycin drug interactions should be expected. Rifampin use requires increased dosing of raltegravir and maraviroc and discontinuation of etravirine, while rifabutin requires higher dosing with efavirenz, lower dosing with ritonavir-boosted protease inhibitors, and lower dose of maraviroc ART. [2]

Monthly monitoring of liver-associated enzymes during LTBI therapy is appropriate.

Combination LTBI therapy with rifapentine plus isoniazid may soon offer the possibility of one-month rather than conventional nine-month isoniazid therapy. [7] A randomized open-label phase three trial in high-risk locales (prevalence 60 cases per 100,000 population) in 10 countries showed one month of rifapentine 300 mg daily plus isoniazid 300 mg daily with pyridoxine was noninferior to isoniazid/pyridoxine alone for 9 months in patients with HIV-positive skin results and patients with HIV-negative skin test results. The endpoint of newly diagnosed active TB or death of TB or unknown cause was 2% in each group after a median of 3.3 years. Drug adherence was higher (97%) in the shorter-course than longer-course LTBI therapy (90%). [17]

M avium complex (MAC) infection

Primary prophylaxis for MAC in people living with HIV infection who immediately initiate ART is no longer recommended, regardless of CD4 count (AII recommendation). [2]

Patients who expect a delayed initiation of ART and have a CD4 count of fewer than 50 cells/μL should be given azithromycin 1200 mg orally weekly after ruling out disseminated MAC infection on clinical assessment (AI recommendation). Alternatives include clarithromycin 500 mg orally twice daily (AI recommendation) or rifabutin 300 mg orally daily with drug dose modifications noted above (BI recommendation).

Toxoplasma gondii infection

Patients with a CD4 count below 100 cells/μL who are not previously known to be seronegative for toxoplasmal immunoglobulin G (IgG) should receive prophylaxis for toxoplasmosis. Trimethoprim-sulfamethoxazole, one double-strength tablet orally once daily is preferred (AII recommendation). Dapsone alone is ineffective against toxoplasmosis. Therefore, dapsone 50 mg orally daily plus pyrimethamine 50 mg orally weekly plus leucovorin 25 mg orally weekly is appropriate for both PCP and toxoplasmosis (BI recommendation). Alternatively, atovaquone with or without pyrimethamine/leucovorin can be considered. [2]

Varicella-zoster virus infection

HIV-infected patients should generally avoid close contact with persons with zoster or chickenpox.

Because the varicella and zoster vaccines are live-virus vaccines, they should not be administered to persons with HIV and CD4 counts lower than 200 cells/µL (AIII recommendation). The current guidelines continue to recommend varicella immune globulin (AIII recommendation) for postexposure prophylaxis, but this requires an IND application and call to the manufacturer. The latest guideline offers a BIII recommendation to consider a 7- to 10-day course of acyclovir or valacyclovir in this situation. [2]


Patients exposed to a sex partner with a diagnosis of primary, secondary, or early latent syphilis within the past 90 days should receive benzathine penicillin G 2.4 million units intramuscularly as a single dose (AII recommendation). [2]


Patients with a CD4 count of less than 150 cells/μL at high risk for exposure or who live in a hyperendemic area should receive itraconazole 200 mg PO daily (BI recommendation). [2]


Patients with a new positive immunoglobulin M (IgM) or IgG serologic test result who live in endemic areas and have a CD4 count of less than 250 cells/μL should receive fluconazole 400 mg PO daily (BIII recommendation). [2]

Penicilliosis (recently renamed talaromycosis)

Patients with a CD4 count of less than 100 cells/μL living or staying in rural endemic areas of Southeast Asia should receive itraconazole 200 mg PO daily (BI recommendation). [2]

Cryptococcal disease

While US guidelines do not recommend screening or prophylaxis of cryptococcal disease, a 2018 supplemental guideline from WHO recommends the following based on high prevalence and mortality in Africa: screening adult and adolescent patients with a CD4 count < 100 cells/µL not suspected of meningitis for cryptococcal antigen followed by preemptive therapy (short-course one-week amphotericin B deoxycholate [1 mg/kg/day] plus flucytosine [100 mg/kg/day divided into 4 doses per day] followed by 1 week of fluconazole 1200 mg/day in adults, 12 mg/kg/day in children and adolescents up to 800 mg daily)) prior to ART (strong recommendation; moderate-certainty evidence). Such therapy "should be considered" in antigen-positive adults and adolescents with a CD4 count < 200 cells/µL (conditional recommendation; moderate-certainty evidence). In the absence of available antigen screening, fluconazole prophylaxis (200 mg/day) should be given to adults and adolescents with HIV infection who have a CD4 count < 100 cells/µL (strong recommendation, moderate-certainty evidence) and "may be considered" in patients with a CD4 count of 100-200 cells/µL (conditional recommendation; moderate-certainty evidence). This guideline considers it "a good practice principal" to perform a lumbar puncture with opening pressure in all patients who are cryptococcal antigen-positive. [18]


Generally Recommended Vaccines

All HIV-positive adolescents and adults who have never had a pneumococcal vaccine should receive a single dose of PCV13 at presentation (AI recommendation). If CD4 cell count is higher than 200 cells/µL, they should receive a 23 valent polysaccharide vaccine (PPV23) at least 8 weeks later (AII recommendation). Those with a CD4 cell count of less than 200 cells/µL should preferably wait until the CD4 count is higher than 200 cells/µL with antiretroviral therapy (ART) before receiving the PPV23 (BIII recommendation). PCV13 should be given to patients who have previously received PV23 (AII recommendation) more than a year prior (AII recommendation). [2]

Other recommended vaccinations are as follows:

  • Hepatitis B virus infection - All susceptible (anti-HBc-negative) patients should receive the 3-dose hepatitis B vaccine (AII recommendation)
  • Influenza virus infection - All patients should receive inactivated trivalent influenza vaccine annually before the influenza season (AIII recommendation)
  • Hepatitis A virus infection - All susceptible (anti-HAV-negative) patients should receive the 2-dose hepatitis A vaccine (AII recommendation)
  • The 9-valent recombinant human papillomavirus (HPV) vaccine (0.5 mL at 0, 1-2, and 6 months) is recommended in HIV-positive males and females aged 13-26 years (AIII recommendation), even if they have received previous bivalent or quadrivalent vaccines (CIII recommendation). [2]
  • Meningococcal ACWY - Two doses 2 months apart and every 5 years
  • Tetanus, diphtheria, and pertussis - Tdap if not previously vaccinated, followed by Td booster every 10 years
  • Measles, mumps, rubella - Two-dose series at least 1 month apart in adults and adolescents without historical or serological evidence of immunity and a CD4 count >200 cells/µL
  • Varicella - Two-dose series at least 3 months apart in adults and adolescents without historical or serological evidence of immunity and a CD4 count >200 cells/µL

Rarely Indicated Primary Prophylaxis

Fungal or yeast infections

According to current NIH guidelines, Cryptococcus neoformans and Candida infections do not warrant primary prophylaxis. [2] In the case of Cryptococcus infection, primary prophylaxis has not been shown effective in Thailand. [14] New WHO guidelines recommend cryptococcal antigen testing and preemptive therapy in antigen-positive patients with a CD4 count < 100 cells/uL in Africa and other areas of high prevalence. [18] Prolonged suppressive therapy for Candida is not recommended owing to risk of resistance. However, if necessary because of frequent recurrence or severe disease, fluconazole 100 mg PO thrice weekly for thrush (BI recommendation), fluconazole 100-200 mg daily (esophagitis) (BI), or fluconazole 150 mg PO once weekly (vaginitis) (CII recommendation) are the first recommended drugs. [2]

Fortunately, aspergillosis and phycomycosis (mucormycosis) are rare in individuals infected with HIV. These infections should be considered in patients with invasive sinusitis and focal pulmonary lesions but do not warrant prophylaxis.

Travelers to malaria-prone areas should have malaria prophylaxis, and those who live in such areas should practice preventative measures, such as the use of treated mosquito netting.

Bacterial infections

Prophylaxis (primary or secondary) for the following community-acquired and healthcare-associated infections is seldom indicated, although these infections are not uncommon in patients infected with HIV:

Persons infected with HIV are at high risk for sexually transmitted diseases such as syphilis, chlamydia, and gonorrhea. These should be reported to authorities and treated with documented cure and provision of counseling to avoid reinfection. Individuals exposed to a sex partner with a diagnosis of primary, secondary, or tertiary syphilis should be treated prophylactically with benzathine penicillin G 2.4 million units intramuscularly one time (AII recommendation).

Nocardia infection is rare in even late stages of AIDS, probably because it is inhibited serendipitously by P carinii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole.

Protozoal and helminthic infections

Patients infected with HIV are at risk for infections with Cryptosporidium species, Giardia species, Isospora species, Cyclospora species, and Microsporidia species, as well as Entamoeba species and Strongyloidiasis species in some locales and with exposure to animals, especially animals with diarrhea. Neither primary nor secondary prophylaxis is indicated. Concomitant malaria and HIV disease is a major problem in Africa, but trimethoprim-sulfamethoxazole may have some prophylactic benefit. [23]

Patients with risk factors for Chagas disease and who are seropositive for Trypanosoma cruzi who have not been previously treated and do not have advanced cardiomyopathy can be considered for a course of either benznidazole or nifurtimox, but efficacy is suboptimal (CIII recommendation), while prompt ART therapy may prevent reactivation of parasitic disease (BIII recommendation). [2]

Other viral infections

Recurrent genital and, occasionally, oral herpes simplex infections, zoster, molluscum contagiosum, and human papillomavirus infections are common. Primary infections are best avoided. Recurrent herpes simplex and zoster may be prevented with acyclovir 400 mg twice daily, continued indefinitely (AI recommendation). The efficacy of the 9-valent recombinant human papillomavirus (HPV) vaccine to prevent warts and neoplasia is unknown in adult patients infected with HIV, but it is recommended for men and women aged 13-26 years (see above). [2] Progressive multifocal leukoencephalopathy (JC virus) is not susceptible to prophylaxis, and no therapy other than immuno-reconstitution is recommended. [2] HHV-8 infection is not specifically treated, but HIV viral therapy plus chemotherapy is given for Kaposi sarcoma.


Secondary Prophylaxis

Secondary prophylaxis (now called maintenance therapy in the NIH/CDC guidelines) consists of therapy given to prevent relapse of known and appropriately treated opportunistic infections that have occurred prior to effective antiretroviral therapy (ART). For most of these infections, the initial treatment is much more intensive and may last for 2-4 weeks, followed by the secondary prophylaxis regimen. This is particularly noteworthy for cryptococcal meningitis, which must be treated initially with amphotericin and flucytosine.

For P carinii pneumonia (PCP), the recommended secondary prophylaxis is trimethoprim-sulfamethoxazole, a double-strength tablet orally daily (AI recommendation), until the CD4 count exceeds 200 cells/μL for 3 months (BII recommendation).

For toxoplasmosis, the following is recommended: sulfadiazine 500-1000 mg orally 4 times daily plus pyrimethamine 25-50 mg orally daily and leucovorin 10-25 mg orally daily (AI recommendation) until the CD4 count exceeds 200 cells/μL for 6 months (AIII recommendation). An additional agent must be added to prevent PCP.

For tuberculosis, it is important to collect specimens for culture and probes before therapy is started. Initial-phase therapy consists of 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol daily or 5-7 times per week per directly observed therapy (AI recommendation). The continuation phase, after ensuring drug susceptibility and repeat cultures, consists of daily isoniazid and rifampin or rifabutin for 6 months for pulmonary tuberculosis, 9 months for pulmonary tuberculosis in which cultures remained positive after the initial two months of therapy, 9-12 months for extrapulmonary tuberculosis with CNS involvement, 6-9 months for extrapulmonary tuberculosis with bone or joint involvement, and 6 months for disease limited to other sites (all BII recommendations).

For M avium complex (MAC) infection, the following is recommended: clarithromycin 500 mg orally twice daily plus ethambutol 15 mg/kg orally daily with or without rifabutin 300 mg orally daily for 12 months until patients have no signs or symptoms of MAC disease and until the CD4 count is greater than 100 cells/μL for 6 months (AII recommendation).

For cytomegalovirus (CMV) retinitis, maintenance therapy for immediate vision-threatening lesions close to the fovea consists of intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection) for 1-4 doses over 7-10 days (AIII recommendation) plus valganciclovir 900 mg PO BID for 14-21 days, then 900 mg PO once daily (AI recommendation). Therapy for peripheral lesions consists of systemic antiviral therapy (various regimens of ganciclovir, valganciclovir, foscarnet, and cidofovir) (AII recommendation). Maintenance therapy for central or peripheral lesions should be continued for at least 3-6 months and until lesions are inactive and the CD4 count has risen to more than 100 cells/μL (AII recommendation). Maintenance therapy should be stopped only after ophthalmological consultation. Quarterly retinal examinations are indicated during the follow-up period after stopping therapy (AIII recommendation). The duration of initial therapy for CMV gastrointestinal disease is 21-42 days or until signs and symptoms have resolved (CII recommendation). The use of maintenance therapy for CMV gastrointestinal, pulmonary, or neurological disease is not established but should probably be individualized, especially during relapses or immune reconstitution reactions.

For cryptococcal meningitis, after initial liposomal amphotericin and flucytosine therapy for at least 2 weeks, give fluconazole 400 mg orally or intravenously daily as "consolidation" therapy (AI recommendation). This should be followed by "maintenance" therapy with fluconazole 200 mg PO daily for at least 1 year (AI recommendation) and until the CD4 count exceeds 100 cells/μL for 3 months (BII recommendation).

Similarly, initial treatment for moderate to severely disseminated histoplasmosis consists of liposomal amphotericin B for induction of at least two weeks, followed by maintenance therapy consisting of itraconazole 200 mg TID for 3 days and then 200 mg BID for 12 months (AII recommendation).

Coccidioidomycosis infections are usually treated with fluconazole for mild disease or amphotericin for severe disease, followed by long-term suppressive therapy with oral fluconazole 400 mg daily or oral itraconazole 200 mg PO BID (AII recommendation).

For mucocutaneous and esophageal Candida infection, long-term suppressive therapy is usually not indicated or necessary, especially if the CD4 count rises above 200 cells/μL (BIII recommendation). Frequent or long-term therapy can result in resistance. If the decision is made to use suppressive therapy, use fluconazole 100 mg orally daily or 3 times weekly for oropharyngeal disease (BI recommendation), fluconazole 100-200 mg orally daily for esophageal disease (BI recommendation), or fluconazole 150 mg orally weekly for vulvovaginal disease (BII recommendation).

For recurrent herpes simplex infection, valacyclovir 500 mg PO BID or acyclovir 400 mg PO daily is recommended as long-term suppression (AI recommendation). The ongoing need for continued suppression should be evaluated yearly as the CD4 cell count rises with antiretroviral therapy.

For recurrent methicillin-resistant S aureus (MRSA) infection, the recommendation is mupirocin 2% nasal ointment to each nostril twice daily for 5 days if colonization is documented. Long-term efficacy is uncertain, and resistance may develop. Germicidal soaps have been recommended for perineal colonization, but little evidence suggests efficacy. Hygienic measures should be emphasized for this epidemic problem.


Questions & Answers


What is the role of opportunistic infection prevention in the treatment of HIV infection?

What is the focus of HIV guidelines on the prevention of opportunistic infections?

How were the CDC/NIH/IDSA guidelines for preventing opportunistic infections in patients with HIV structured?

What is the role of exposure avoidance in the prevention of opportunistic infections in patients with HIV infection?

When is antimicrobial prophylaxis indicated for the prevention of opportunistic infections in patients with HIV infection?

What is the role of CD4 counts in the selection of antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

What are risks of antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

What are the possible adverse drug reactions from antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

Which tests are performed prior to initiation of antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

What is the role of vaccines in the prevention of opportunistic infections in patients with HIV infection?

What is included in the monitoring of antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

What are the clinical landmarks for terminating antimicrobial prophylaxis for the prevention of opportunistic infections in patients with HIV infection?

What is the primary prophylaxis against P carinii pneumonia (PCP) in patients with HIV infection?

What is the primary prophylaxis against latent Mycobacterium tuberculosis infection (LTBI) in patients with HIV infection?

What is the primary prophylaxis against M avium complex (MAC) in patients with HIV infection?

What is the primary prophylaxis against toxoplasma gondii infection in patients with HIV infection?

What is the primary prophylaxis against varicella-zoster virus infection in patients with HIV infection?

What is the primary prophylaxis against syphilis in patients with HIV infection?

What is the primary prophylaxis against histoplasmosis in patients with HIV infection?

What is the primary prophylaxis against coccidioidomycosis in patients with HIV infection?

What is the primary prophylaxis against penicilliosis (talaromycosis) in patients with HIV infection?

Which vaccines are administered to prevent opportunistic infections in patients with HIV infection?

What is the role of prophylaxis against fungal or yeast infections in patients with HIV infection?

What is the role of prophylaxis against bacterial infections in patients with HIV infection?

What is the role of prophylaxis against protozoal and helminthic infections in patients with HIV infection?

What is the role of prophylaxis against viral infections in patients with HIV infection?

What is secondary prophylaxis (maintenance therapy) for the prevention of relapse of opportunistic infections in patients with HIV infection?

What is used as secondary prophylaxis against P carinii pneumonia (PCP) in patients with HIV infection?

What is used as secondary prophylaxis against toxoplasmosis in patients with HIV infection?

What is used as secondary prophylaxis against tuberculosis in patients with HIV infection?

What is used as secondary prophylaxis against M avium complex (MAC) infection in patients with HIV infection?

What is used as secondary prophylaxis against cytomegalovirus (CMV) retinitis in patients with HIV infection?

What is used as secondary prophylaxis against cryptococcal meningitis in patients with HIV infection?

What is used as secondary prophylaxis against histoplasmosis in patients with HIV infection?

What is used as secondary prophylaxis against coccidioidomycosis infections in patients with HIV infection?

What is used as secondary prophylaxis against Candida infection in patients with HIV infection?

What is used as secondary prophylaxis against herpes simplex infection in patients with HIV infection?

What is used as secondary prophylaxis against MRSA infection in patients with HIV infection?