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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
HIV-1 Associated Opportunistic Infections
Angel A. Justiz Vaillant; Roopa Naik.
Author Information
Last Update: July 2, 2020.
Introduction
Human immunodeficiency virus (HIV) is a retrovirus known to attack the CD4+ T lymphocytes.
Of the two subtypes, HIV-1 and HIV-2, the former is common and prevalent worldwide, and the
latter is confined to West Africa and hence less common. In individuals with chronic HIV
infection not on treatment with antiretroviral agents, as the CD4+ count drops they are vulnerable
to a multitude of infections which rarely occur in an immunocompetent host, hence the term
opportunistic infections (OIs). The presence of an AIDS-defining illness or CD4+ less than 200
cells/mm³ is necessary for defining AIDS and the literature describes potentially fatal
opportunistic infections in these patients which are often challenging to treat.
Etiology
HIV infected individuals, even with high CD4+ cell counts, are at a higher risk of developing
both common and OIs than the general population. However, in HIV patients with CD4+ cell
counts less than 200 cells per millimeter, the risk of developing OIs and subsequent death
remains the highest.[1] These individuals are prone to a wide variety of bacterial, viral, fungal
and protozoal infections which include Toxoplasma gondii, Pneumocystis jirovecii (previously
Pneumocystis carinii), Cryptococcus neoformans, Mycobacterium avium, Mycobacterium
tuberculosis, Cytomegalovirus, Herpes simplex viruses, Histoplasma capsulatum.
Epidemiology
In 2015, 1.1 million people were estimated to be living in the US with HIV.[2] It has an
estimated worldwide prevalence of 36.7 million as of 2017. Health authorities recognize the
disease as a global health problem. Transmission of HIV infection is common via unprotected
sexual contact, highest in male-to-male sexual contact in the US with a reported 70% of new
HIV infections, followed by injection drug users, contaminated blood transfusions. Vertical
transmission during or after birth from the mother to the newborn may also occur. The successful
initiation of antiretroviral therapy (ART) has lowered the occurrence of HIV-related opportunistic
infections. However, patients who present in the late stages of HIV or are unable to maintain
viral suppression remain a high risk for opportunistic infections.
Pathophysiology
An HIV-1 virion consists of two identical strands of RNA and associated enzymes, including
reverse transcriptase packaged in a cone-shaped core composed of p24 capsid protein with a
surrounding p17 protein matrix, all enclosed by a phospholipid membrane envelope derived from
the host cell. Glycoproteins, gp41 and gp120, are bound to the envelope. CD4+ and chemokine
receptors on the host cell surface function as HIV-1 receptors.
The HIV life cycle starts with the virion binding to CD4+ and chemokine receptor. Fusion of
HIV membrane with cell membrane occurs, followed by the entry of the viral genome into the
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cytoplasm. Reverse transcriptase mediates the synthesis of proviral DNA leading to the
integration of provirus into the cell genome. Subsequently, cytokine activation of the cell,
transcription of HIV genome, transport of spliced and unspliced RNAs to cytoplasm occur.
Synthesis of HIV proteins and assembly takes place and finally the expression of gp120/gp41 on
the cell surface, and budding of mature virion transpires. An infected cell produces many virions
that are capable of infecting CD4+ cells, macrophages, and neurons, thereby amplifying the
infectious cycle.
The pathognomonic feature of HIV is the progressive reduction in the CD4+ T cells, leading to
the destruction of both cell-mediated and antibody-mediated immune mechanisms.
History and Physical
History and physical should aim at localizing the affected organ system, concurrently with the
CD4+ cell counts. Since these opportunistic infections are manifested depending on the severity
of the suppression of CD4+ counts, for this review, they have been categorized accordingly.
All CD4+ counts
Mycobacterium tuberculosis:
Following infection with Mycobacterium tuberculosis, the bacilli can persist for years, referred to
as latent TB infection (LTBI). An estimated 3 to 16% of untreated HIV patients have the annual
risk of reactivation with TB disease, whereas the lifetime risk among HIV-negative persons with
LTBI is about approximately 5%.[3] This organism can involve every organ system. Symptoms
include fatigue, weakness, weight loss, and fever. Pulmonary tuberculosis features chronic cough
and spitting of blood. Meningitis and urinary tract involvement may occur. Disseminated
bloodstream infections lead to lesions in many organs (miliary tuberculosis) and are associated
with a high mortality rate.
CD4+ count less than 250 cells/mm^3
Coccidioidomycosis:
Consists of two species, Coccidioidesimmitis, and Coccidioides posadasii, found in soil. Four
different syndromes are noted: (1) focal pneumonia presenting with fever, cough and pleuritic
chest pain, (2) diffuse pneumonia with fever, dyspnea, hypoxemia, (3) meningitis with headache,
lethargy, and (4) positive serology tests without evidence of localized infection.[4]
CD4+ count < 200 cells/mm^3
Pneumocystis jirovecii pneumonia (PCP):
This fungus, until recently, was thought to be a protozoan. History of fever, progressive dyspnea,
non-productive cough and hypoxemia on the exam are characteristic. Chest x-ray shows diffuse,
bilateral, symmetrical interstitial infiltrates with a ground glass pattern.[5]
Mucocutaneous candidiasis:
The causative organism is Candida albicans. Oropharyngeal infections present as painless,
creamy, white, plaque-like lesions in the oral cavity. These lesions scrape off easily. Angular
cheilosis is another feature. Esophageal candidiasis can present with retrosternal burning pain,
odynophagia. Endoscopic testing reveals white plaques as seen in the oral cavity. In women with
HIV, vulvovaginal candidiasis presents with mucosal burning and itching.
CD4+ count < 150 cells/mm^3
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Histoplasma capsulatum:
In immunocompetent individuals, acute pulmonary histoplasmosis is characterized by fever,
myalgia, chills, headaches, and a nonproductive cough. These symptoms resolve spontaneously
without therapy. In patients with AIDS and some elderly patients without HIV, chronic
pulmonary histoplasmosis occurs as a reactivation process. Severe disseminated histoplasmosis
manifesting as fever, fatigue, cough, weight loss, lymphadenopathy, hepatosplenomegaly,
mucocutaneous ulcers of the nose, mouth, tongue, and intestine may occur.
CD4+ count < 100 cells/mm^3
Cryptococcus neoformans:
It is a yeast that is characterized by a thick polysaccharide capsule. Can manifest as subacute
meningitis or meningoencephalitis. Fever, malaise, headache are the common presenting
symptoms. Pulmonary cryptococcosis can present with fever, chest pain, cough, dyspnea,
positive blood cultures.[6]
Cryptosporidiosis:
This condition results from the protozoa, Cryptosporidium. Typically associated with infections
of the small bowel and causes diarrhea, however, in a profoundly immunosuppressed state may
be associated with severe, extraintestinal cryptosporidiosis. Watery diarrhea with abdominal
pain, nausea and vomiting are common.
Herpes simplex viruses (HSV):
Patients with AIDS suffer frequent and severe HSV infections including oropharyngeal disease,
keratoconjunctivitis, genital herpes, eczema herpeticum, encephalitis, and neonatal herpes. HSV
proctitis, with deep, extensive, nonhealing ulcers, generally seen in male patients in sexual
relations with male HIV patients.
Microsporidiosis:
They are ubiquitous organisms, predominantly zoonotic or waterborne. Many species are
reported to cause infections in human. Clinical presentations differ by the causative
species. Encephalitozoon bieneusi can cause diarrhea, malabsorption, and cholangitis. E. cuniculi
lead to hepatitis, encephalitis, and disseminated disease. E. intestinalis can cause diarrhea,
disseminated infection, and superficial keratoconjunctivitis. E. hellem can cause superficial
keratoconjunctivitis, sinusitis, prostatic abscesses, and disseminated
infection. Anncaliia and Trachipleistophora cause keratoconjunctivitis, myositis.
Trachipleistophora can cause encephalitis and disseminated disease.
JC virus infection:
Manifested as progressive multifocal leukoencephalopathy (PML). It is characterized by focal
demyelination.[7] Symptoms vary based on the brain area involved and can range from weakness
in one extremity to hemiparesis, aphasia. Optic nerves are never involved, and it rarely affects
the spinal cord.[8] PML can develop as a response to immune reconstitution secondary to ART.
These patients can have atypical features including mass effect from the PML lesions with
surrounding edema referred to as inflammatory PML.[9] Fever and headaches are not typical
and may suggest a concomitant opportunistic infection. Seizures can present when lesions are
close to the cortex.
CD4+ count < 50 cells/mm^3
Cytomegalovirus:
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The most common manifestation is retinitis. Often unilateral, but ultimately leads to bilateral
involvement. Other presentations such as colitis, esophagitis, ventriculoencephalitis present.
CMV pneumonitis is not common.
Mycobacterium avium complex (MAC):
It is one of the most common opportunistic bacterial infections in the AIDS population in the US.
It can involve any organ and leads to persistent bacteremia and extensive infiltration of the
tissues resulting in organ dysfunction. In the lung, nodules and cavitary lesions are common.
Other manifestations include pericarditis, soft tissue abscesses, skin lesions, lymph node
enlargement, central nervous system lesions, and bone infection.
Toxoplasma gondii encephalitis:
It is a coccidian protozoan of worldwide distribution. Focal encephalitis is the most common
presentation.[10] Symptoms of fever, confusion, headaches, or motor weakness should be
promptly worked up.
Bartonellosis:
Bartonella henselae and Bartonella quintana are associated with infections in HIV patients.
[11] Bacillary angiomatosis (BA), and bacillary peliosis hepatitis only present in
immunocompromised patients.[12] BA is hematogenously spread, and hence lesions are seen in
most organ systems, but skin manifestations are the easiest to diagnose. Fever, weight loss, night
sweats are common. B. henselae causes bacillary peliosis hepatitis and B. quintana is associated
with osteomyelitis and culture-negative endocarditis.
Coexisting infections with HIV
Syphilis:
Manifestations are similar to patients without HIV infection. Primary syphilis presents as a
solitary, painless nodule at the point of contact which ulcerates quickly to form chancre. Primary
lesions, however, may be absent in HIV patients.[13] Secondary syphilis, which usually
manifests 2 to 8 weeks after inoculation can cause mucocutaneous lesions, associated with fever,
malaise, headache, and lymphadenopathy. Condyloma lata can occur which is a flat, moist,
papular lesions in warm intertriginous areas. Hepatitis, pneumonia, nephrotic syndrome have
been reported. Tertiary syphilis involves the cardiovascular system and gummatous disease
affecting any organ system. Neurosyphilis may occur in any stage of syphilis. Manifestations
include cranial nerve abnormalities, stroke. Concomitant meningitis and uveitis may be more
common in HIV patients.[14]
Human papillomavirus infection:
Major risk factor for cervical cancer.[15] Majority of manifestations are mucosal infections
leading to genital, anal and oral warts. These are flat, papular or pedunculated growths on the
mucosa of the epithelium. They are usually asymptomatic. Intraepithelial neoplasia can manifest
as bleeding, pain or a palpable mass.
Hepatitis B virus infection:
It is the leading cause of chronic liver disease.[16] Acute infection is asymptomatic in about 70%
of patient and leads to fulminant hepatic failure in less than 1%.[17] Symptoms include nausea,
vomiting, abdominal pain predominantly in the right upper quadrant, fever, with or without
jaundice. In patients with HIV infection, there is a higher risk of developing chronic HBV
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infection, which is defined as persistent detection of HBsAg on two different occasions 6 months
apart.[18] [19] Late manifestations include liver cirrhosis and hepatocellular carcinoma.
Hepatitis C virus infection:
They are minimally symptomatic in both acute and chronic infections. Low-grade fever,
abdominal pain in the right upper quadrant, nausea, vomiting, and anorexia along with jaundice
characterize the presentation. Long term complications include cirrhosis, which is seen in
approximately 20% of patients with chronic HCV infections within 20 years after infection.[20]
Evaluation
In all HIV infected patients, regular monitoring of CD4+ cell counts is necessary for the
early diagnosis and treatment of opportunistic infections. CD4+ counts also help in the initiation
of prophylactic treatment regimens in the appropriate patients. Infection-specific diagnostic tests
are listed below.
Mycobacterium tuberculosis: All HIV positive patients require testing for LTBI. Tuberculin skin
test (TST) is performed and considered positive when there is a greater than 5 mm induration at
48 to 72 hours in HIV positive patients, without any clinical or radiologic signs of TB disease.
Limitations include reduced specificity in patients who have received Bacillus Calmette-Guerin
(BCG) vaccination, reduced sensitivity in advanced immunodeficiency and the need to call
patients for two visits, to place the test and to read it. Interferon-gamma release assays (IGRA)
are FDA approved, consistent, and have higher specificity (92 to 97%) compared to (56 to 95%)
for TST. An incidental finding of fibrotic lesions on chest x-ray should prompt further diagnostic
testing for LTBI and active infection. Sputum samples for AFB smear and culture must be
obtained, including from asymptomatic patients. The only patient populations excluded from
these testings are those with prior active TB who have completed treatment. In HIV positive
individuals whose CD4+ counts are less than 200 cells/mm^3, the presence of fibrotic lesions on
chest x-ray which are highly suggestive of TB infection must be considered as having an active
infection and subsequently, should be started on empiric treatment while performing further
testing and awaiting results.[21]
Coccidioidomycosis: Isolation of the organism on culture is part of the diagnosis, and so is the
visualization of the spherules on histopathologic evaluation of the affected tissue. Cerebrospinal
fluid (CSF) analysis for complement fixation IgG antibody is often used in the detection of
coccidioidal meningitis. CSF cultures demonstrate positive results in less than 30% of patients
with meningitis. Coccidioidal IgG and IgM serology are seldom positive in individuals with low
CD4+ counts. Blood cultures are generally positive in diffuse pulmonary involvement.[21]
Pneumocystis jirovecii pneumonia: Demonstration of the organism in tissue, bronchoalveolar
lavage fluid or induced sputum samples is necessary for the diagnosis. Giemsa, Diff-Quik, and
Wright stains are used to detect the cyst and trophozoite forms but not the cyst wall. Gomori
methenamine silver, toluidine blue, and cresyl violet are used to stain the cyst wall. Beta-Dglucan is found in fungal cell walls could be elevated in patients with PCP; however, needs
further evaluation of both the sensitivity and specificity.[21]
Mucocutaneous candidiasis: Oropharyngeal candidiasis are diagnosed clinically based on the
appearance and the ability to scrape off the white plaques. These lesions can be visualized using
a potassium hydroxide (KOH) preparation which reveals yeast forms on microscopy. Endoscopy
is necessary to diagnose esophageal candidiasis coupled with the demonstration of Candida yeast
forms in tissues along with the isolation of Candida in cultures. Vulvovaginal candidiasis can be
diagnosed clinically followed by the demonstration of yeast forms using KOH preparation.[21]
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Histoplasma capsulatum: Disseminated histoplasmosis is diagnosable by detecting Histoplasma
antigen in blood or urine. However, it is not sensitive to pulmonary infections. Peripheral blood
smears may show the organisms engulfed by WBCs. The organism grows slowly and hence
requires weeks for culture isolation; They have been cultured from bone marrow, blood,
respiratory secretions in greater than 85% of AIDS patients. CSF cultures are rarely positive, and
hence the diagnosis of meningitis is difficult. Detection of either anti-Histoplasma antibodies or
Histoplasma antigen in the CSF is diagnostic and is positive in about 70% of cases.[22]
Cryptococcus neoformans: In patients with meningitis or meningoencephalitis, Cryptococcal
antigen is easily detected in the CSF, as well as in the serum. Positive blood cultures present in
up to 75% of HIV positive patients with cryptococcal meningitis.[21]
Cryptosporidiosis: Microscopic identification of the oocytes in stool or tissue as well as their
detection by direct immunofluorescence or enzyme-linked immunosorbent assay (ELISA).[21]
Herpes simplex viruses (HSV): HSV DNA PCR, viral culture and HSV antigen detection are
utilized for the detection of mucocutaneous lesions. All genital lesions must undergo typing as
HSV-2 more commonly correlates with genital lesions than HSV-1.
Microsporidiosis: These microsporidia can be detected by light microscopy using stains such as
Chromotrope 2R, calcofluor white and Uvitex 2B which can help differentiate between the
spores of the microsporidia and the cells and debris (e.g., stool). In patients with gastrointestinal
symptoms, if the stool testing is negative and the infection is suspected, small bowel biopsy must
be considered.[23]
JC virus infection: PML diagnosis is by clinical and neuroradiologic clues. MRI findings of
white matter lesions which are hyperintense (bright) on T2-weighted images and hypointense
(dark) on T1-weighted sequences, in areas corresponding to the clinical deficits present in most
cases. PCR can be utilized to detect JCV DNA in CSF. Perivascular mononuclear inflammatory
infiltration present on histopathology.[9]
Cytomegalovirus: Detection of CMV viremia by PCR occurs in both end-organ disease and
without an end-organ state. A negative IgG level helps to look for an alternate etiology for
symptoms. CMV retinitis diagnosis occurs with the help of an ophthalmoscopic examination
which has a positive predictive value of 95%.[21] CMV colitis is diagnosed by the demonstration
of mucosal ulcerations on endoscopy or colonoscopy. Biopsy of these lesions
shows characteristic intranuclear and intracytoplasmic inclusions on the histopathologic exam.
[24] In patients with CD4+ counts under 50 cells/mm^3, a regular fundoscopic exam is a
requirement.
Mycobacterium avium complex (MAC): Growth of MAC from cultures of blood, lymph node,
or any other sterile tissues or body fluids along with the clinical signs and symptoms are useful in
the diagnosis of disseminated MAC infection.[25]
Toxoplasma gondii encephalitis (TE): Detection of anti-toxoplasma immunoglobulins G
antibodies is noted in a majority of HIV positive patients with TE. Furthermore, a combination of
clinical signs with imaging findings on CT or MRI of mass lesions, coupled with
the demonstration of the organisms on brain biopsy is necessary for a definitive diagnosis.[21]
Bartonellosis: BA lesions have a characteristic vascular proliferation with the demonstration of
numerous bacilli on a modified silver stain. Gram stain and acid-fast staining are negative and
not helpful. Bartonella species are difficult to culture but have been isolated using EDTA tubes.
[21] CDC has developed a well-characterized serologic test which is available in some state
health labs.[26]
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Syphilis: Direct visualization of Treponema pallidum by darkfield microscopy, biopsy with silver
stain or direct fluorescent anti-Treponema antibody; treponemal tests (FTA-ABS or TP-PA);
serologic diagnosis using Venereal Disease Research Laboratory [VDRL] and rapid plasma
reagin [RPR] have been used. Neurosyphilis is diagnosed by CSF examination which may show
mononuclear pleocytosis, reactive CSF-VDRL or normal to mildly elevated protein
concentration.[27]
Human papillomavirus infection: Visual inspection of the warts is usually sufficient to make the
diagnosis, although confirmation is obtained via biopsy. There is currently no role for HPV
testing in HIV positive women. In these patients, if their cervical Pap test shows ASCUS, ASCH, LSIL, HSIL they require referral for colposcopy.[21]
Hepatitis B virus infection: All HIV positive individuals require testing for HBV infection.
Testing, specifically, for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (antiHBc total), and hepatitis B surface antibody (anti-HBs) is necessary to identify those who have
received preventative vaccination or in the diagnosis of chronic hepatitis B. In patients with
chronic HBV, HBeAg, anti-HBe and HBV DNA must be tested to evaluate for the levels of
replicating virus and progression of liver disease, progression to HCC and responses to therapy,
respectively.[21]
Hepatitis C virus infection: Detection of anti-HCV in blood is necessary for all patients with
HIV.[28] Qualitative or quantitative testing for plasma HCV RNA usually confirms chronic
infection. Liver biopsy is reserved for the evaluation of HCV-related complications like fibrosis,
assess prognosis and help with treatment options.[29]
Treatment / Management
All patients with HIV/AIDS are candidates for highly active antiretroviral therapy (HAART).
This therapy has shown a reduction in the morbidity and mortality, in addition to lowering the
risk of transmitting the infection to others. Drug dosing is once daily. For example:
Rilpivirine/emtricitabine/tenofovir disoproxil is a tablet that contains 25 mg rilpivirine,
200 mg emtricitabine, and 245 mg tenofovir disoproxil
Rilpivirine/tenofovir alafenamide/emtricitabine is a tablet with 25 mg rilpivirine, 25 mg
tenofovir alafenamide, and 200 mg emtricitabine
Dolutegravir/abacavir/lamivudine is an antiretroviral drug combination containing 50 mg
dolutegravir, 600 mg abacavir, and 300 mg lamivudine
Management of opportunistic infections in HIV/AIDS is tailored based on the causative
organisms
Toxoplasma gondii: In patients who are Toxoplasma-seropositive and with CD4+ counts less
than 100 cells/mm^3 prophylactic double strength daily dose of trimethoprim-sulfamethoxazole
(TMP-SMX) should be initiated. The alternative prophylactic regimen is dapsone-pyrimethamine
and leucovorin. Acute infections can be treated with a combination of pyrimethamine and
sulfadiazine and leucovorin. Alternative drugs include spiramycin, clindamycin, trimethoprimsulfamethoxazole. Spiramycin is the recommendation for use in pregnancy to prevent congenital
transmission. Anticonvulsants may be useful in patients with a history of seizures who have TE
but are not recommended as prophylaxis.[21]
Pneumocystis jirovecii: All HIV positive patients, including pregnant women, must be started on
TMP-SMX for chemoprophylaxis when their CD4+ count is less than 200
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cells/mm^3. Alternative prophylactic medications include dapsone, dapsone plus pyrimethamine
plus leucovorin, atovaquone and aerosolized pentamidine. PCP is treated with TMP-SMZ which
is the drug of choice. Other drugs include dapsone, TMP, clindamycin plus primaquine or IV
pentamidine, atovaquone suspension. Aerosolized pentamidine is not used to treat PCP.
Recommended duration of therapy is 21 days.[21]
Cryptococcus neoformans: Combination therapy of flucytosine and amphotericin B is the
treatment of choice for cryptococcal meningitis. An alternative regimen of fluconazole and
flucytosine are options, although it is inferior to amphoterin B.[30] Duration of combination
therapy is 2 weeks, following which, after confirmation of a negative CSF culture on repeat
lumbar puncture, they can be discontinued and started on fluconazole 400 mg daily for 8 weeks.
Following this, the dose is reduced to 200 mg daily for 1 year. Secondary prophylaxis must be
reinitiated when the CD4+ counts less than 100 cells/mm^3.[21]
Mycobacterium avium complex (MAC): MAC organisms are resistant to first-line
antituberculosis therapy. Clarithromycin is the preferred drug of choice and the first agent along
with ethambutol (second drug) for the initial treatment of MAC. Rifabutin has been added as the
third drug. Azithromycin may be used when clarithromycin cannot be tolerated due to drug
interactions or patient intolerance. The fourth agents that can be used are either levofloxacin or
moxifloxacin.[21] Clofazimine should not be used due to increased mortality and lack of
efficacy. Primary prophylaxis is not recommended in patients with HIV unless their CD4+ cells
count are less than 50 cells/mm^3.[31]
Mycobacterium tuberculosis: Drug-susceptible TB infection is treated for 6 months using
a combination of isoniazid (INH), pyrazinamide (PZA), rifampin (RIF) or rifabutin, and
ethambutol (EMB) for 2 months by directly observed therapy (DOT), followed by INH and RIF
for 4 months. In patients with cavitary disease noted on chest X-ray or those with positive
cultures, the treatment should be for a total of 9 months with an additional 3 more months of INH
and RIF. All patients receiving INH therapy must be prescribed pyridoxine supplements.
Extrapulmonary TB except for CNS disease, bone, and joint involvement, should be treated for 6
to 9 months (2 months of INH, PZA, RIF, and EMB, followed by 4 to 7 months of INH and
RIF). In patients with CNS, bone, and joint diseases, treatment must be for 9 to 12 months.
Intermittent dosing has better medication compliance rates when administered by DOT and
achieves higher peak serum concentration.[21]
Cytomegalovirus: Oral or IV ganciclovir, IV foscarnet, IV cidofovir has been used successfully
to treat life-threatening cytomegalovirus infection in people with CMV retinitis. In pregnancy,
intravitreous ganciclovir coupled with valganciclovir is given in the first trimester for retinal
disease.
Herpes simplex viruses: Both orolabial and genital HSV lesions are treatable with oral
acyclovir, valacyclovir or famciclovir. Duration of treatment is 5 to 10 days. IV acyclovir can be
used for severe mucocutaneous lesions.
Histoplasma capsulatum: IV liposomal amphotericin B is used in severe disseminated
histoplasmosis. Duration of treatment is 2 weeks followed by 3 days of oral itraconazole 200 mg
3 times daily and finally 200 mg daily for at least 12 months.
Coccidioidomycosis: Fluconazole or itraconazole are options in the treatment of mild disease as
well as meningitis. Itraconazole is used for bone or joint disease, while amphoterin B is used for
pulmonary involvement. Posaconazole or voriconazole are also possibilities, although the data is
limited.[21]
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Mucocutaneous candidiasis: Oral fluconazole is the drug of choice. Both itraconazole and
posaconazole solutions are as effective as fluconazole but less tolerated. Esophageal candidiasis
can be treated with a 14 to 21-day therapy of oral or IV fluconazole or oral itraconazole.
Vulvovaginal candidiasis is treatable with oral fluconazole, topical azoles (clotrimazole,
miconazole) or oral itraconazole solution.[21]
Cryptosporidiosis: ART must be initiated in patients with a goal to restore CD4+ cells count
greater than 100 cells/mm^3 as this leads to the resolution of clinical cryptosporidiosis. Diarrheal
losses should be adequately repleted either orally or by the IV route. Multiple agents
including nitazoxanide, spiramycin, paromomycin, bovine dialyzable leukocyte extract,
and bovine hyperimmune colostrum are studied, but none of these are effective consistently
without concurrent ART use.[32]
Microsporidiosis: ART must be initiated in patients with a goal to restore CD4+ cells count over
100 cells/mm^3 as this leads to the resolution of clinical microsporidiosis.
JC virus infection: There is no definitive treatment available for JCV. Initiation of ART
to reverse immunosuppression is the main therapy in these patients.
Bartonellosis: Doxycycline and erythromycin have been used to treat BA, bacteremia, peliosis
hepatis, bone infections successfully. Duration of the therapy is usually long and requires
treatment for at least 3 months. CNS infections receive treatment with doxycycline with or
without RIF. Azithromycin can be used in patients with concerns for medication compliance.
[21]
Syphilis: Penicillin is the drug of choice. Early syphilis can be treated with benzathine penicillin.
Neurosyphilis can be treated with IV aqueous crystalline penicillin G or procaine penicillin
for 10 to 14 days. Tertiary syphilis involves complex management and must always include a
specialist to guide the course of the treatment.
Human papillomavirus infection: Oral and genital warts are difficult to treat as more than one
medications are often necessary for refractory or recurrent lesions. Podophyllotoxin, imiquimod,
cryotherapy, trichloroacetic acid (TCA), or bichloroacetic acid are all options with varying
efficacy. Surgical treatments are very effective and include electrocautery, tangential shave
excision, curettage, tangential scissor excision, electrosurgery, infrared coagulation. A specialist
must address all cancerous lesions.
Hepatitis B virus infection: In HIV/HBV coinfections, fixed-dose formulations of tenofovir
disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine are the treatment of
choice due to their anti-HBV activity. Lamivudine or emtricitabine, if used long term, as the only
drug active against HBV, can lead to a high rate of HBV drug-resistance mutations.
Hepatitis C virus infection: Emphasis should be on starting ART at the earliest in these patients
to reduce the risk of progression of liver disease. HCV infection is not preventable with
vaccinations. There is also no post-exposure prophylaxis. Treatment of chronic hepatitis C is
based on the viral genotype and is beyond the scope of this review.
Differential Diagnosis
Central nervous system toxoplasmosis:
CNS lymphoma
CNS vasculitis
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Brain abscess
Rubella
Newborn hemolytic anemia
Infections caused by Cryptococcus neoformans, Aspergillus species and Nocardia species
Mycosis fungoides
Sarcoidosis
Bacterial sepsis
Syphilis
Tuberculosis
Tularemia
Acute HIV infection
Cytomegalovirus retinitis
Cytomegalovirus encephalitis
Cytomegalovirus ventriculitis
CNS tuberculosis
Disseminated tuberculosis
Leukemia
Lymphoma
Progressive multifocal leukoencephalopathy
Fungal endophthalmitis
Intraocular foreign body
Ocular manifestations of syphilis
Anterior granulomatous uveitis
Anterior nongranulomatous uveitis
Toxocariasis
Primary intraocular lymphoma
Herpes simplex infection
Histoplasmosis
Listeriosis
Pneumocystis jirovecii pneumonia:
Acute respiratory distress syndrome
Cytomegalovirus infection
Lymphocytic interstitial pneumonia
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Mycoplasma infection
Viral pneumonia
Legionellosis
Tuberculosis
Cryptococcus neoformans:
Acanthamoeba infection
Basal cell carcinoma
Aspergillus abscess
Pyogenic abscess
Nocardial abscess
Mycoses
Chronic, benign lymphocytic meningitis
Hemorrhages
Lymphomas
Meningeal metastases
Histoplasmosis
Molluscum contagiosum
Pneumocystis jirovecii pneumonia
Lipoma
Tuberculosis
Syphilis
Toxoplasmosis
Mycobacterium avium complex (MAC):
Mumps
Parotid Tumor
Mycobacterium scrofulaceum infection
Nontuberculous mycobacterial infections
Lung cancer
Lymphoma
Aspergillosis
Bartonellosis
Cytomegalovirus
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Blastomycosis
Actinomycosis
Mycobacterium marinum infection
Tuberculosis
Histoplasmosis
Hypersensitivity pneumonitis
Sarcoidosis
Mycobacterium tuberculosis:
Tularemia
Actinomycosis
Mycobacterium avium complex infection
M. chelonae infection
M. fortuitum infection
M. gordonae infection
M. kansasii infection
M. marinum infection
Squamous cell carcinoma
Endemic syphilis
Erythema induratum (nodular vasculitis)
Erythema nodosum
Leprosy
Leishmaniasis
Cat scratch disease
Syphilis
Actinomycosis
Aspergillosis
Bronchiectasis
Constrictive pericarditis
Fungal pneumonia
Histoplasmosis
Lung abscess
Nocardiosis
Non-small cell lung cancer
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Cytomegalovirus:
HIV/AIDS
Enteroviruses
Autoimmune hepatitis
Human herpesvirus 6 infection
Infectious mononucleosis
Toxoplasmosis
Viral hepatitis
Herpes simplex encephalitis:
Apsetic meningitis
Neuro-Behcet disease
Benign childhood epilepsy
Intracranial epidural abscess
Haemophilus meningitis
CNS complications in HIV
Intracranial hemorrhage
Migraine headache
Neurosyphilis
Paraneoplastic encephalomyelitis
Histoplasma capsulatum:
Sarcoidosis
Aspergillosis
Aspiration pneumonitis and pneumonia
Chlamydial pneumonia
Fungal pneumonia
Bacterial pneumonia
Blastomycosis
Carcinoid lung tumors
Legionellosis
Coccidioidomycosis and Valley fever
Mediastinal cysts
Mediastinal lymphoma
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Mycoplasma infection
Pneumococcal infection
Pneumocystis jirovecii pneumonia
Viral pneumonia
Tuberculosis
Prognosis
The prognosis of opportunistic infections in AIDS remains poor; however, improving patient
compliance with ART may lead to fewer infections, in turn improving overall outcomes in HIV
positive patients.[33]
Complications
Patients with HIV/AIDS are prone to opportunistic infections given their immunosuppressed
state; this risk is exaggerated with the weakening of the immune system as the disease
progresses. In addition to the infections, some of the noninfectious complications include HIVrelated encephalopathy, high-grade B-cell lymphoma, HIV-induced wasting syndrome, HIV
associated nephropathy.[34]
Enhancing Healthcare Team Outcomes
Management of HIV patients is best accomplished with the help of an interprofessional team of
healthcare professionals that includes the infectious disease specialist, pharmacist, internist,
infection control specialty nurses, and other specialists depending on the organ infected. This
approach demonstrates the best chances for optimal patient care and therapeutic success. [Level
V]
The pharmacist has to emphasize medication compliance and regular follow up of HIV
seropositive individuals. Education on the importance of checking serial CD4+ counts and its
implications in initiating chemoprophylaxis to prevent opportunistic infections must be
emphasized at every clinic visit. Safe sex practices, needle disposal education in intravenous
drug users are highly encouraged to reduce the spread of HIV infection.
Continuing Education / Review Questions
Access free multiple choice questions on this topic.
Earn continuing education credits (CME/CE) on this topic.
Comment on this article.
References
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