1. Weight Changes

Weight loss is a particularly distressing complication of long-standing HIV infection. Patients typically have disproportionate loss of muscle mass, with maintenance or less substantial loss of fat stores. The mechanism of HIV-related weight loss is not completely understood but appears to be multifactorial, with some of the older thymidine analog medications implicated. In the setting of the newer medications, weight gain has been seen with some ART regimens, with integrase strand transfer inhibitors associated with greater weight gain than protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Among nucleoside/tide reverse transcriptase inhibitors, tenofovir alafenamide is associated with greater weight gain than tenofovir disoproxil fumarate or abacavir.

2. Nausea

Nausea leading to weight loss is sometimes due to esophageal candidiasis. Patients with oral candidiasis and nausea should be empirically treated with an oral antifungal agent. Patients with weight loss due to nausea of unclear origin may benefit from use of antiemetics or promotility agents prior to meals (ondansetron, 8 mg three times daily; prochlorperazine, 10 mg three times daily; or metoclopramide, 10 mg three times daily). Dronabinol (5 mg three times daily) or medical cannabis can also be used to treat nausea, although in some individuals it can worsen nausea and vomiting. Depression and adrenal insufficiency are two potentially treatable causes of weight loss.

1. Pneumocystis Pneumonia

(See also Part 38.) P jirovecii pneumonia is the most common opportunistic infection associated with AIDS. Pneumocystis pneumonia may be difficult to diagnose because the symptoms-fever, cough, and shortness of breath-are nonspecific and typically subacute. Furthermore, the severity of symptoms ranges from fever and no respiratory symptoms through mild cough or dyspnea to frank respiratory distress.

Hypoxemia may be severe, with a PO₂ less than 60 mm Hg. The cornerstone of diagnosis is the CXR or CT scan (Figure 33-2). Diffuse or perihilar infiltrates are most characteristic, but only two-thirds of patients with Pneumocystis pneumonia have this finding. Normal CXRs are seen in 5-10% of patients with Pneumocystis pneumonia, although sensitivity is increased with CT scanning, while the remainder have diffuse ground glass opacities. Severe cases can lead to pneumothoraces. Large pleural effusions are uncommon with Pneumocystis pneumonia; their presence suggests bacterial pneumonia, other infections such as tuberculosis, or pleural Kaposi sarcoma.

Figure 33-2. Pneumocystis Pneumonia in a Haitian Woman (She/Her) in Whom Underlying HIV/AIDS is Suspected

Pneumocystis pneumonia in a Haitian woman (she/her) in whom underlying HIV/AIDS is suspected. Typical CXR showing bilateral diffuse interstitial infiltrates extending out from the hilar areas. (Reproduced, with permission, from Grippi MA, Elias JA, Fishman JA et al (editors). Fishman's Pulmonary Diseases and Disorders, 5th ed. McGraw-Hill, 2015.)

Definitive diagnosis can be obtained in 70-90% of cases by Wright-Giemsa stain or direct fluorescence antibody (DFA) test of induced sputum. Increasingly, PCR testing is available and has high sensitivity and specificity. Sputum induction is performed by having patients inhale an aerosolized solution of 3% saline produced by an ultrasonic nebulizer. Patients should not eat for at least 8 hours and should not use toothpaste or mouthwash prior to the procedure since they can interfere with test interpretation. The next step for patients with negative sputum examinations in whom Pneumocystis pneumonia is still suspected should be bronchoalveolar lavage. This technique establishes the diagnosis in over 95% of cases.

In patients with symptoms suggestive of Pneumocystis pneumonia but with negative or atypical CXRs and negative sputum examinations, other diagnostic tests may provide additional information in deciding whether to proceed to bronchoalveolar lavage. Elevation of serum LD occurs in 95% of cases of Pneumocystis pneumonia, but the specificity of this finding is at best 75%. A normal serum beta-glucan test makes Pneumocystis pneumonia unlikely, although a variety of factors can cause a false-positive serum beta-glucan test. Either a normal diffusing capacity of carbon monoxide (DL_CO) or a high-resolution CT scan of the chest that demonstrates no interstitial lung disease makes the diagnosis of Pneumocystis pneumonia very unlikely. In addition, a CD4 count greater than 250 cells/mcL within 2 months prior to evaluation of respiratory symptoms makes a diagnosis of Pneumocystis pneumonia unlikely; only 1-5% of cases occur above this CD4 count level (see Figure 33-1). This is true even if the patient previously had a CD4 count lower than 200 cells/mcL but has had an increase with ART. Pneumothoraces can be seen in people with HIV with a history of Pneumocystis pneumonia.

Trimethoprim-sulfamethoxazole is the preferred treatment of Pneumocystis pneumonia (Table 33-3. Treatment of AIDS-Related Opportunistic Infections and Malignancies (Listed in Alphabetical Order)). In addition to specific anti-Pneumocystis treatment, corticosteroid therapy has been shown to improve the course of patients with moderate to severe P jirovecii pneumonia (PaO₂ less than 70 mm Hg on room air or alveolar-arterial O₂ gradient greater or equal to 35 mm Hg) when administered within 72 hours of the start of anti-Pneumocystis treatment. Steroids should be started as early as possible after initiation of treatment, using prednisone 40 mg orally twice daily for days 1-5, 40 mg daily for days 6-10, and 20 mg daily for days 11-21 (for patients who cannot take oral medication, intravenous methylprednisolone can be substituted at 75% of the oral dose). The mechanism of action for the steroids to improve outcomes is presumed to be a decrease in alveolar inflammation.

2. Other Infectious Pulmonary Diseases

Other infectious causes of pulmonary disease in patients with AIDS include bacterial, mycobacterial, and viral etiologies.

B. MYCOBACTERIAL- Tuberculosis occurs in an estimated 4.2% of persons in the United States who have HIV. Patients with active tuberculosis and CD4 counts above 350 cells/mcL are likely to present with upper lobe and hilar infiltrates and paratracheal adenopathy, findings similar to persons without HIV (Figure 33-3). With advanced immunodeficiency, lower lobe, middle lobe, interstitial, and miliary infiltrates are more common, along with mediastinal adenopathy and extrapulmonary involvement. Although a purified protein derivative (PPD) test or an interferon-gamma release assay (IGRA, including the QuantiFERON and T-SPOT tests) should be performed on all people with HIV in whom a diagnosis of tuberculosis is being considered, the lower the CD4 cell count, the greater the likelihood of falsely negative PPD or IGRA test results or of indeterminate IGRA test results. It is recommended to repeat PPD or IGRA testing following improvement in the CD4 count for those with CD4 count less than 200 cells/mcL. Because "anergy" skin test panels do not accurately classify those patients who are infected with tuberculosis but unreactive to the PPD, they are not recommended.

Figure 33-3. A 36-Year-Old Man (He/Him) with Pulmonary Tuberculosis

A 36-year-old man (he/him) with pulmonary tuberculosis. There is an opacification of a portion of the left upper lung in association with a cavity, findings consistent with pulmonary tuberculosis. Also, there is an infiltrate in the right lung. The extent of his disease raises the specter that he has underlying HIV/AIDS. (Reproduced with permission from Richard P. Usatine, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H. The Color Atlas of Family Medicine, 3rd ed. McGraw-Hill, 2019.)

In cases of active tuberculosis, treatment of people with HIV is similar to that of people without HIV. However, rifampin should not be given to patients receiving a boosted protease inhibitor (PI) regimen. In these cases, rifabutin may be substituted, but it may require dosing modifications depending on the antiretroviral regimen. Tenofovir alafenamide should not be used with rifampin and should be substituted for tenofovir disoproxil fumarate (TDF). Dolutegravir may be given with rifampin but should be dose adjusted to twice daily. Multidrug-resistant tuberculosis has been a major problem in several metropolitan areas of the developed world, and cases of "extremely resistant" tuberculosis in patients with HIV are an important global concern. Nonadherence with prescribed antituberculous medications is a major risk factor. Several of the reported outbreaks appear to implicate nosocomial spread. The emergence of medication resistance makes it essential that antibiotic sensitivities be performed on all positive cultures. Medication therapy should be individualized. Patients with multidrug-resistant (MDR) M tuberculosis infection should receive at least three medications to which their organism is sensitive. The rise of MDR TB and extensively resistant TB in Eastern Europe and Russia has prompted increasing use of bedaquiline/pretomanid/linezolid-based regimens.

Atypical mycobacteria can cause pulmonary disease in patients with AIDS with or without preexisting lung disease and responds variably to treatment. Distinguishing between M tuberculosis and atypical mycobacteria is typically accomplished using M tuberculosis nucleic acid amplification (NAA) if available, which can also identify rifampin resistance rapidly, or via culture. DNA probes allow for presumptive identification usually within days of a positive culture. Definitive species identification for nontuberculous mycobacteria typically requires culture of sputum specimens. While awaiting definitive diagnosis, if clinical suspicion is high, clinicians should err on the side of treating patients as if they have M tuberculosis infection. Clinicians may wait for definitive diagnosis if the person is smear-negative for acid-fast bacilli, M tuberculosis NAA negative, clinically stable, and not living in a communal setting. It is important to note that isolated M avium complex pneumonia is relatively uncommon in AIDS, so diagnostic work-up for unexplained pneumonia should continue if preexisting structural lung disease is not present.

BlancFXet al; STATIS ANRS 12290 Trial Team. Systematic or test-guided treatment for tuberculosis in HIV-infected adults. N Engl J Med. 2020;382:2397. [PMID: 32558469] Centers for Disease Control and Prevention (CDC). Provisional CDC guidance for the use of pretomanid as part of a regimen [bedaquiline, pretomanid, and linezolid (BPaL)] to treat drug-resistant tuberculosis disease. 2022 Feb. http://www.cdc.gov/tb/topic/drtb/bpal/default.htm KerkhoffADet al. VirtualCROI 2020: tuberculosis and coinfections in HIV infection. Top Antivir Med. 2020;28:455. [PMID: 32886465] LapinelNCet al. Prevalence of non-tuberculous mycobacteria in HIV-infected patients admitted to hospital with pneumonia. Int J Tuberc Lung Dis.2019;23:491. [PMID: 31064629]

3. Noninfectious Pulmonary Diseases

4. Sinusitis

Chronic sinusitis can be a frustrating problem for people with HIV. Symptoms include sinus congestion and discharge, headache, and fever. Some patients may have radiographic evidence of sinus disease on sinus CT scan in the absence of significant symptoms.

1. Toxoplasmosis

Toxoplasmosis used to be one of the most common CNS space-occupying lesion in people with HIV. Headache, focal neurologic deficits, seizures, or altered mental status may be presenting symptoms. The diagnosis is usually made presumptively based on the characteristic appearance of cerebral imaging studies in an individual known to be seropositive for Toxoplasma. Typically, toxoplasmosis appears as multiple contrast-enhancing lesions on CT scan that do not reduce on diffusion on MRI scan. Lesions tend to be peripheral, with a predilection for the basal ganglia.

Single lesions are atypical of toxoplasmosis. When a single lesion has been detected by CT scanning, MRI scanning may reveal multiple lesions because of its greater sensitivity. If a patient has a single lesion on MRI and is neurologically stable, clinicians may pursue a 2-week empiric trial of toxoplasmosis therapy. A repeat scan should be performed at 2 weeks. If the lesion has not diminished in size, biopsy of the lesion should be performed. A positive Toxoplasma serologic test does not confirm the diagnosis because many people with HIV have detectable titers without having active disease. Conversely, less than 3% of patients with toxoplasmosis have negative titers. Therefore, negative Toxoplasma titers in a patient with HIV infection and a space-occupying lesion should be a cause for aggressively pursuing an alternative diagnosis. The preferred treatment of toxoplasmosis is with pyrimethamine and sulfadiazine (Table 33-3. Treatment of AIDS-Related Opportunistic Infections and Malignancies (Listed in Alphabetical Order)). If pyrimethamine is not available, patients can be treated with oral trimethoprim-sulfamethoxazole.

2. Cns Lymphoma

Primary non-Hodgkin lymphoma is the second most common CNS space-occupying lesion in people with HIV. Symptoms are similar to those with toxoplasmosis. While imaging techniques cannot distinguish these two diseases with certainty, lymphoma more often is solitary. Other less common lesions should be suspected if there is preceding bacteremia, tuberculosis risk factors, fungemia, or injection drug use. These include bacterial abscesses, cryptococcomas, tuberculomas, and Nocardia lesions.

Stereotactic brain biopsy should be strongly considered if lesions are solitary or do not respond to toxoplasmosis treatment, especially if they are easily accessible. Diagnosis of lymphoma is important because many patients benefit from treatment (radiation therapy). A positive PCR assay of CSF for Epstein-Barr virus (EBV) DNA is consistent with a diagnosis of lymphoma; a PCR for EBV DNA in CSF is 100% sensitive and 98.5% specific for AIDS-associated primary CNS lymphoma, making it useful as a diagnostic tumor marker.

3. HIV-Associated Dementia and Neurocognitive Disorders

Patients with HIV-associated neurocognitive disorders, including dementia typically have difficulty with cognitive tasks (eg, memory, attention), exhibit diminished motor function, and have emotional or behavioral problems. Patients may first notice a deterioration in their handwriting. The manifestations of cognitive impairment or dementia may wax and wane, with persons exhibiting periods of lucidity and confusion over the course of a day. The diagnosis of HIV-associated dementia most commonly occurs in untreated patients with advanced HIV infection, and is one of exclusion based on a brain imaging study and on spinal fluid analysis that excludes other pathogens. Neuropsychiatric testing is helpful in distinguishing patients with dementia from those with depression. Many patients improve with ART. However, slowly progressive neurocognitive deficits may still develop in patients taking ART as they age.

Metabolic abnormalities may also cause changes in mental status: hypoglycemia, hyponatremia, hypoxia, and drug overdose are important considerations in this population. Other less common infectious causes of encephalopathy include progressive multifocal leukoencephalopathy (discussed below), CMV, syphilis, and herpes simplex encephalitis.

4. Cryptococcal Meningitis

Cryptococcal meningitis typically presents with fever and headache. Less than 20% of patients have meningismus. Diagnosis is based on a positive latex agglutination test of serum or CSF that detects cryptococcal antigen (or "CrAg") or positive culture of spinal fluid for Cryptococcus. Approximately 99% of patients with cryptococcal meningitis have a positive serum CrAg. Thus, a negative serum CrAg test makes a diagnosis of cryptococcal meningitis unlikely and can be useful in the initial evaluation of a patient with headache, fever, and normal mental status. Treatment has three phases: induction, consolidation, and maintenance. Induction treatment is given for a minimum of 2 weeks plus evidence of clinical improvement and a negative CSF culture on repeat lumbar puncture. The preferred induction treatment is liposomal amphotericin with flucytosine (Table 33-3. Treatment of AIDS-Related Opportunistic Infections and Malignancies (Listed in Alphabetical Order)), followed by an oral fluconazole treatment, and then secondary prophylaxis. Prophylaxis can be stopped if the patient is asymptomatic, has a CD4 cell count of greater than 100/mcL for at least 3 months, and has suppressed viral load on ART. Of note, a 2022 study showed that an alternative induction regimen of just a single dose of liposomal amphotericin B with 14 days of flucytosine and concomitant fluconazole was noninferior to the longer course of amphotericin B; this can be considered an alternative approach in resource-limited settings or if liposomal amphotericin B is not tolerated.

5. Meningococcal Meningitis

People with HIV infection are at increased risk for bacterial meningococcal disease. Treatment is the same as in people without infection. The Advisory Committee on Immunization Practices recommends the meningococcal conjugate vaccine routinely (serogroups A, C, W, and Y) for all persons aged 2 months or older with HIV infection. In settings of meningococcal outbreaks, the meningococcal B vaccine may be administered to adolescents and young adults with HIV, not necessarily all patients with HIV, for short-term protection against most strains of serogroup B meningococcal disease. Routine administration of meningococcal B vaccine to patients with HIV, however, is not indicated.

6. HIV Meningitis and HIV Myelopathy

HIV meningitis, characterized by lymphocytic pleocytosis of the spinal fluid with negative culture, is common early in HIV infection. Spinal cord function may also be impaired in individuals with HIV infection. HIV myelopathy presents with leg weakness and incontinence. Spastic paraparesis and sensory ataxia are seen on neurologic examination. Myelopathy is usually a late manifestation of HIV disease, and most patients will have concomitant HIV encephalopathy. Pathologic evaluation of the spinal cord reveals vacuolation of white matter. Because HIV myelopathy is a diagnosis of exclusion, symptoms suggestive of myelopathy should be evaluated by lumbar puncture to rule out CMV polyradiculopathy (described below) and an MRI or CT scan to exclude epidural lymphoma.

7. Progressive Multifocal Leukoencephalopathy (PML)

PML is a viral infection (with the JC polyomavirus) of the white matter of the brain seen in patients with very advanced HIV infection. It typically results in focal neurologic deficits such as aphasia, hemiparesis, and cortical blindness. Imaging studies are strongly suggestive of the diagnosis if they show non-enhancing white matter lesions without mass effect; the diagnosis is verified by JC virus positivity via PCR in the CSF. Patients can stabilize or improve after ART initiation; there is no other treatment. In the setting of wide-scale ART and because PML occurs at very low CD4 counts, the prevalence of this condition is rare.

1. Candidal and other Esophagitis

(See also Part 17.) Esophageal candidiasis is a common AIDS complication. In a patient with characteristic symptoms, empiric antifungal treatment is begun with fluconazole (200-400 mg orally daily for 14-21 days). Improvement in symptoms should be apparent within 1-2 days of antifungal treatment. If there is no improvement, fungal culture to exclude fluconazole resistance, and further evaluation to identify other causes of esophagitis (herpes simplex, CMV) is recommended.

2. Hepatic Disease

3. Biliary Disease

Cholecystitis presents with manifestations similar to those seen in immunocompetent hosts but is more likely to be acalculous. Sclerosing cholangitis and papillary stenosis have also been reported in people with HIV. Typically, the syndrome presents with severe nausea, vomiting, and right upper quadrant pain. Liver enzymes generally show alkaline phosphatase elevations disproportionate to elevation of the aminotransferases. Although dilated ducts can be seen on ultrasound, the diagnosis is made by endoscopic retrograde cholangiopancreatography, which reveals intraluminal irregularities of the proximal intrahepatic ducts with "pruning" of the terminal ductal branches. Stenosis of the distal common bile duct at the papilla is commonly seen. CMV, Cryptosporidium, and microsporidia are thought to play inciting roles in this syndrome, but these conditions are rarely seen unless the patient is experiencing very advanced HIV-related immunodeficiency.

4. Enterocolitis

5. Other Disorders

Two other important GI abnormalities in people with advanced AIDS are gastropathy and malabsorption. It has been documented that some people with HIV do not produce normal levels of stomach acid and therefore are unable to absorb medications that require an acid medium. This decreased acid production may explain, in part, the susceptibility of people with HIV to Campylobacter, Salmonella, and Shigella, all of which are sensitive to acid concentration. There is no evidence that Helicobacter pylori is more common in people with HIV.

A malabsorption syndrome occurs commonly in patients with AIDS. It can be due to infection of the small bowel with M avium complex, Cryptosporidium, or microsporidia.

1. Viral Dermatitides

A. HERPES SIMPLEX INFECTIONS- These infections (Figure 33-5) occur more frequently, tend to be more severe, and are more likely to disseminate in patients with AIDS than in immunocompetent persons. Because of the risk of progressive local disease, all herpes simplex attacks should be treated for 5-10 days with valacyclovir (1000 mg orally twice daily), acyclovir (400 mg orally three times a day), or famciclovir (250 mg orally three times a day) (Table 33-3. Treatment of AIDS-Related Opportunistic Infections and Malignancies (Listed in Alphabetical Order)). To avoid the complications of attacks, many clinicians recommend suppressive therapy for people with HIV with a history of recurrent herpes. Options for suppressive therapy include valacyclovir (1000 mg orally daily), acyclovir (400 mg orally twice daily), or famciclovir (250 mg orally twice daily). Long-term suppressive herpes prophylaxis with acyclovir does not reduce HIV transmission between heterosexual men and women from low- and middle-income countries.

Figure 33-5. Herpes Simplex Viral Skin Infection, Frequently Found in Men (He/Him) with HIV

Herpes simplex viral skin infection, frequently found in men (he/him) with HIV. Shown are grouped vesicles typical of herpes simplex on the penis, with both intact vesicles of initial eruption and visible crusts of resolving lesions. (Reproduced, with permission, from Eric Kraus, MD, in: Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H. The Color Atlas and Synopsis of Family Medicine, 3rd ed. McGraw-Hill, 2019.)

B. VARICELLA ZOSTER- This is a common manifestation of HIV infection (eFigure 33-3). Patients with varicella zoster infections should be treated for 7-10 days with valacyclovir (1000 mg three times a day) or famciclovir (500 mg orally three times a day). Acyclovir can also be used, but it requires more frequent dosing (800 mg orally five times per day for 7 days). Vesicular lesions should be cultured if there is any question about their origin, since herpes simplex requires much lower doses of acyclovir than does varicella zoster. Disseminated zoster and cases with ocular involvement should be treated with intravenous acyclovir (10 mg/kg every 8 hours for 7-10 days). The recombinant zoster vaccine (Shingrix, two doses administered 2-6 months apart) should be given to people with HIV, and there is no longer an age requirement in these patients. Because it is not a live virus like the previous zoster vaccine (Zostavax), it is not contraindicated in patients with immune deficiency-but, based on other vaccines, people with HIV are likely to develop more robust immune response to the vaccine when their CD4 count is greater than 200/mcL.

eFigure 33-3. Herpes Zoster

Herpes zoster. A painful vesicular eruption developed over the right forehead in this 44-year-old with HIV infection. Herpes zoster was diagnosed clinically and confirmed by a positive direct fluorescent antibody test on fluid from one of the vesicles. (Reproduced with permission from Richard P. Usatine, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr., Chumley H. The Color Atlas of Family Medicine, 2nd ed. McGraw-Hill, 2013.)

HarbeckeRet al. Herpes zoster vaccines. J Infect Dis. 2021;224:S429. [PMID: 34590136]

C. MOLLUSCUM CONTAGIOSUM- This infection is caused by a pox virus and is seen in people with HIV, as in other immunocompromised patients. The characteristic umbilicated fleshy papular lesions (eFigure 33-4) have a propensity for spreading widely over the patient's face and neck (Figure 33-6) and should be treated with topical liquid nitrogen.

eFigure 33-4. Molluscum Contagiosum

Molluscum contagiosum. Close-up of a molluscum contagiosum lesion showing a dome-shaped pearly papule with a characteristic umbilicated center. (Reproduced with permission from Richard P. Usatine RP, Smith MA, Mayeaux EJ Jr., Chumley H. The Color Atlas and Synopsis of Family Medicine, 3rd ed. McGraw-Hill, 2019.)

Figure 33-6. Molluscum Contagiosum

Molluscum contagiosum. Extensive molluscum contagiosum lesions on the face of a young person, suggestive of HIV. (Reproduced with permission from Richard P. Usatine, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H. The Color Atlas of Family Medicine, 3rd ed. McGraw-Hill, 2019.)

2. Bacterial Dermatitides

B. BACILLARY ANGIOMATOSIS- It is caused by two closely related organisms: Bartonella henselae and Bartonella quintana. The epidemiology of these infections suggests zoonotic transmission from fleas of infected domestic cats (henselae) or contact with human body louse feces (quintana). The most common manifestation is raised, reddish, highly vascular skin lesions (eFigure 33-5) that can mimic lesions of Kaposi sarcoma. Fever is a common manifestation of this infection; involvement of bone, lymph nodes, liver (peliosis hepatis due to B henselae) and endocarditis have also been reported. The infection is treated with doxycycline, 100 mg orally twice daily and rifampin, 300 mg orally twice daily for a prolonged period depending on the seriousness of the infection. Patients who are seriously ill with visceral involvement or endocarditis may require at least 6 months of therapy.

eFigure 33-5. Bacillary Angiomatosis

Bacillary angiomatosis. Bacillary angiomatosis is a systemic infection caused by Bartonella species. Its cutaneous lesions appear as scattered papules and nodules (like the one shown here) or as abscesses. In people with HIV, bacillary angiomatosis most often occurs when the CD4 count is below 200/mcL. It can be treated with antibiotics. (Reproduced, with permission, from Usatine RP, Moy RL, Tobinick EL, Siegel DM. Skin Surgery: A Practical Guide. Mosby, 1998. Copyright © Elsevier.)

MantisJet al. Cat-scratch disease in an AIDS patient presenting with generalized lymphadenopathy: an unusual presentation with delayed diagnosis. Am J Case Rep. 2018;19:906. [PMID: 30068900] DingFet al. Clinical and echocardiographic characteristics of Bartonella infective endocarditis: an 8-year single-centre experience in the United States. Heart Lung Circ. 2022;31:350. [PMID: 34456130]

3. Fungal Rashes

4. Neoplastic Dermatitides

See Part 6 and the Kaposi sarcoma section below.

5. Nonspecific Dermatitides

1. Kaposi Sarcoma

A. PRESENTATION- Kaposi sarcoma is caused by human herpesvirus-8 (HHV-8) and can occur at any CD4 count although the risk increases at lower CD4 cell counts. Lesions may appear anywhere; careful examination of the eyelids, conjunctiva, pinnae, palate, and toe webs is mandatory to locate potentially occult lesions. In light-skinned individuals, Kaposi lesions usually appear as purplish, nonblanching lesions that can be papular or nodular (eFigure 33-6; eFigure 6-19). In dark-skinned individuals, the lesions may appear browner. In the mouth, lesions are most often palatal papules, though exophytic lesions of the tongue and gingivae may also be seen. Kaposi lesions may be confused with other vascular lesions such as angiomas and pyogenic granulomas. Pulmonary Kaposi sarcoma can present with chronic cough, hemoptysis, or both and is associated with peribronchovascular nodules on CT scan. It can be diagnosed via bronchoscopy following visualization of the typical lesions. Gastrointestinal Kaposi sarcoma most often manifests as GI bleeding. Kaposi sarcoma lesions can occur shortly after initiating ART, especially in patients starting ART who have advanced immunodeficiency. In this situation, Kaposi sarcoma is likely to be an immune reconstitution reaction (see Inflammatory Reactions Common Problems in Infectious Diseases & Antimicrobial Therapy, below).

eFigure 33-6. Kaposi Sarcoma

Kaposi sarcoma. A 35-year-old man presented with several reddish-purple papular lesions on his elbow. When these were diagnosed on shave biopsy as Kaposi sarcoma (KS), he was tested and found to be positive for HIV. Systemic treatment with combination antiretroviral therapy and topical treatment with alitretinoin gel was started, and the KS lesions eventually resolved. (Used, with permission, from Heather Wickless, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H. The Color Atlas of Family Medicine, 2nd ed. McGraw-Hill, 2013.)

2. Non-Hodgkin Lymphoma

3. Hodgkin Disease

Although Hodgkin disease is not included as part of the CDC definition of AIDS, studies have found that HIV infection is associated with a fivefold increase in the incidence of Hodgkin disease. HIV-infected persons with Hodgkin disease are more likely to have mixed cellularity and lymphocyte depletion subtypes of Hodgkin disease and to seek medical attention at an advanced stage of disease.

4. Anal Dysplasia and Squamous Cell Carcinoma

These lesions are generally a result of HPV infection and noted in people of all genders with HIV. Although many report a history of anal warts or have visible warts, a significant percentage have silent papillomavirus infection. Cytologic (using Papanicolaou smears) and papillomavirus DNA studies can be performed on specimens obtained by anal swab. Because of the risk of progression from dysplasia to cancer in patients with HIV, regular anal cytologic examinations or high-resolution anoscopy should be performed. An anal Papanicolaou smear is performed by rotating a moistened Dacron swab about 2 cm into the anal canal. The swab is immediately inserted into a cytology bottle. Some experts also recommend high-risk HPV PCR testing be included. In the large ANCHOR study, which involved nearly 4500 individuals with anal high-grade squamous intraepithelial lesions (HGSIL), nine patients who were assigned to aggressive therapy (mostly office-based electrocautery) developed anal cancer compared with 21 of those in an active monitoring group (no treatment), representing a 57% decrease in relative risk of anal cancer over the median 25.8-month follow-up period. This pivotal study has changed care toward more aggressive screening for HGSIL and treatment to prevent progression to anal cancer among people with HIV.

HPV also plays a causative role in cervical dysplasia and carcinoma in women with HIV (discussed below).