PRESENTING PROBLEMS IN HIV INFECTION

Dr Santosh K

Mandya Institute of medical sciences

1

• The clinical consequences of HIV infection encompass a spectrum ranging from an acute syndrome associated with primary infection through a prolonged asymptomatic state to an advanced disease.

2

THE ACUTE HIV SYNDROME

• 50-70% of individuals with HIV infection experience an acute clinical syndrome 3-6 weeks after primary infection.

• The syndrome is typical of an acute viral syndrome .

• Symptoms persist for one to several weeks and gradually subside as an immune response to HIV develops.

3

4

5

• Lymphadenopathy occurs in -70% of individuals with primary HIV infection.

• Most patients recover spontaneously from this syndrome .

• Primary infection with or without the acute syndrome is followed by a prolonged period of clinical latency.

6

THE ASYMPTOMATIC STAGE- CLINICAL LATENCY

• The median time of the asymptomatic stage for untreated patients is about 10 years.

• HIV disease with active virus replication is ongoing and progressive during this asymptomatic period.

• The rate of disease progression is directly correlated with HIV RNA levels.

• Some patients referred to as long-term non-progressors show little decline in CD4+ T cell counts over extended periods of time.

7

• During the asymptomatic period of HIV infection, the average rate of CD4+ T cell decline is ~50/µL per year.

• When the CD4+ T cell count falls to <200/µL, the resulting state of immunodeficiency is severe enough to place the patient at high risk for opportunistic infection and neoplasms .

8

9

SYMPTOMATIC DISEASE

• Diagnosis of AIDS is made in anyone with HIV infection and a CD4+ T cell count <200/ µL .

• Symptoms of HIV disease can appear at any time during the course of HIV infection.

• severe and life-threatening complications of HIV infection occur in patients with CD4+ T cell counts <200/µL .

10

DISEASES OF THE RESPIRATORY SYSTEM

• Acute bronchitis and sinusitis are prevalent during all stages of HIV infection.

• Sinusitis presents as fever, nasal congestion, and headache.

• The maxillary sinuses are most commonly involved; however, ethmoid, sphenoid, and frontal sinuses are also frequently involved.

11

• High incidence of sinusitis results from an increased frequency of infection with encapsulated organisms such as H. influenzaeand Streptococcus pneumoniae.

• patients with low CD4+ T cell counts may have mucormycosis infections of the sinuses.

12

PNEUMONIA

• The most common manifestation of Pulmonary disease is pneumonia.

• S. pneumoniae and H. influenzae are responsible for most cases of bacterial pneumonia in patients with AIDS.

• Consequence of altered B cell function and/or defects in neutrophil function secondary to HIV disease.

• Pneumonias due to S. aureus and P. aeruginosaalso occur with an increased frequency in patients with HIV infection.

13

• Patients with untreated HIV infection have a six fold increase in the incidence of pneumococcal pneumonia and a 100-fold increase in the incidence of pneumococcal bacteremia.

• inflammatory response to pneumococcal infection is proportional to the CD4+ T cell count.

• Due to this high risk of pneumococcal disease, immunization with pneumococcal polysaccharide is generally recommended.

14

PNEUMOCYSTIS JIROVECI INFECTION

• PNEUMOCYSTIS Pneumonia (PCP) was once the hallmark of AIDS.

• single most common cause of pneumonia in patients with HIV and is likely the etiologic agent in 25% of cases of pneumonia in patients with HIV infection.

15

• PCP presents with non productive cough or with scanty white sputum production.

• Patients complain of characteristic retrosternal chest pain , described as sharp or burning type, and worsens on inspiration.

• The disease usually has an indolent course with weeks of vague symptoms.

16

• Patients receiving aerosolized pentamidine for prophylaxis against PCP, show a variety of extra pulmonary infections.

• Otic involvement may present as a polypoid mass involving the external auditory canal.

• Others include ophthalmic lesions of the choroid, necrotizing vasculitis , bone marrow hypoplasia, and intestinal obstruction.

• Other organs involved include lymph nodes, spleen, liver, kidney, pancreas, pericardium, heart, thyroid, and adrenals.

17

18

TUBERCULOSIS

• Worldwide 1/3rd of the AIDS related deaths are associated with TB.

• Patients with HIV infection are more likely to have active TB by a factor of 100.

• Active TB often develops relatively early in the course of HIV infection and may be an early clinical sign of HIV disease.

19

• The clinical manifestations of TB in HIV-infected patients are quite varied and generally show different patterns as a function of the CD4+ T count.

• In patients with relatively high CD4+ T cell counts, the typical pattern of pulmonary reactivation occurs.

• Patients present with fever, cough, dyspnea on exertion, weight loss, night sweats, and a chest x-ray revealing cavitary apical disease of the upper lobes.

20

• In patients with lower CD4+ T cell counts, disseminated disease is more common.

• In these patients the chest x-ray may reveal diffuse or lower lobe bilateral reticulonodular infiltrates consistent with miliary spread, pleural effusions, and hilar or mediastinal adenopathy.

• Infection may be present in bone, brain, meninges, GI tract, lymph nodes and viscera.

21

ATYPICAL MYCOBACTERIAL INFECTION

• Atypical mycobacterial infections are also seen with an increased frequency in patients with HIV infection.

• MAC infection is a late complication of HIV infection, occurring predominantly in patients with CD4+ T cell counts of <50/µL.

• The most common atypical mycobacterial infection is with M. avium or M. intracellularespecies—the Mycobacterium avium complex (MAC). 22

• Prior infection with M. tuberculosis decreases the risk of MAC infection.

• MAC infections arise from organisms that are ubiquitous in the environment, including both soil and water.

• There is also evidence for person-to-person transmission of MAC infection.

• The presumed portals of entry are the respiratory and GI tract.

23

• common presentation is disseminated disease with fever, weight loss, and night sweats,abdominal pain, diarrhea, and lymphadenopathy.

• Bilateral, lower lobe infiltrate suggestive of miliary spread.

• Alveolar or nodular infiltrates and hilar and/or mediastinal adenopathy can also occur.

• Anemia and elevated liver alkaline phosphatase are common.

24

25

OTHER RESPIRATORY INFECTIONS

• Rhodococcus equi is a gram positive, pleomorphic, acid fast non- spore forming bacillus that can cause pulmonary and disseminated infection in HIV infected patients.

• Fever and cough with expectoration are the common presenting complaints.

• X-ray shows cavitary lesions and consolidation.

26

• Coccidioides immitis is a mould that is endemic in the southwest United States.

• It can cause a reactivation pulmonary syndrome in patients with HIV infection.

• Most patients with this condition will have CD4+ T cell counts <250/4.

• Patients present with fever, weight loss, cough, and extensive, diffuse reticulonodular infiltrates on chest x-ray.

• Nodules, cavities, pleural effusions, and hilar adenopathy are also seen.

27

• Invasive aspergillosis is not an AIDS-defining illness and is generally not seen in patients with AIDS in the absence of neutropenia or administration of glucocorticoids.

• Presents as pseudomembranoustracheobronchitis.

• Primary pulmonary infection of the lung may be seen with histoplasmosis.

28

29

IDOPATHIC INTERSTITIAL PNEUMONIA

• Two forms of idiopathic interstitial pneumonia:

a)lymphoid interstitial pneumonitis (LIP)

b)nonspecific interstitial pneumonitis (NIP).

• LIP is a common finding in children.

• This disorder is characterized by a benign infiltrate of the lung and is due to the polyclonal activation of lymphocytes.

• Transbronchial biopsy is diagnostic .

30

DISEASES OF THE CARDIOVASCULAR SYSTEM

• Heart disease is a common postmortem finding in HIV infected person.

• The most common heart disease is coronary heart disease.

• Cardiovascular disease may result from the classical risk factors, a direct consequence of HIV infection or as a result of ART.

31

• Patients with HIV infection have higher levels of triglycerides and lower levels of LDLs .

• Pathogenesis is likely related to the immune activation and increased propensity for coagulation seen as a consequence of HIV replication.

• Exposure to HIV protease inhibitors and certain reverse transcriptase inhibitors has been associated with increase in total cholesterol.

32

• Dilated cardiomyopathy associated with congestive heart failure (CHF)in a HIV infected patient is referred to as HIV-associated cardiomyopathy.

• Generally occurs as a late complication of HIV infection and, histologically, displays elements of myocarditis.

• HIV can be directly demonstrated in cardiac tissue in this setting.

• Patients present with typical findings of CHF including edema and shortness of breath.

33

• Patients may also develop cardiomyopathy as side effects of IFN-α or nucleoside analogue therapy.

• KS, cryptococcosis, Chagas' disease, and toxoplasmosis can involve the myocardium, leading to cardiomyopathy.

• Pericardial effusions may be seen in the setting of advanced HIV infection. Predisposing factors include TB, CHF, mycobacterial infection, cryptococcalinfection, pulmonary infection, lymphoma, and KS.

34

MUCOCUTANEOUS DISEASES

• Mucocutaneous manifestations are common in HIV .

35

36

• Dermatophyte infection involving skin hairs and nails is common .

• 80% of the patients present with seborrhoeic dermatitis.

• It presents as dry scaly erythematous plaques on the face.

• M. furfur is the important causative organism.

37

38

• Major viral infections affecting the skin are herpes zoster (VZV), human papillomavirus (HPV) and molluscum contagiosum.

• Herpes simplex (type 1 or 2): Affect the lips, mouth and skin or anogenital area .

In later-stage HIV, the lesions are usually chronic, extensive, harder to treat and recurrent.

Persistent and severe anogenital ulceration is usually herpetic and a marker for underlying HIV.

39

40

Varicella zoster:

• Presents with a dermatomal vesicular rash on an erythematous base.

• It can occur at any stage but is more frequent with failing immunity.

• The rash may be severe, multidermatomal, persistent or recurrent, or may become disseminated.

• Diagnosis of herpetic lesion can be confirmed by culture, smear preparations ,characteristic inclusion bodies .

41

• HPV infection is usually anogenital.

• Warts on hands and feet are also common.

• Molluscum contagiosum is found in about 10% of the HIV infected patients. They present with papules with central umbilications involving the face , neck and scalp region.

• Scabies may cause intensely prutitic encrusted papules ( NORWEGIAN Scabies)with secondary infection affecting almost the whole of the body.

42

43

44

CANDIDIASIS:

• Almost exclusively mucosal, affecting nearly all patients with CD4 counts < 200/µL . Nearly always caused by C. albicans.

• Pseudo membranous candidiasis presents as white patches on the buccal mucosa that can be scraped off to reveal a red raw surface .

• Tongue, palate and pharynx are involved.

• Hypertrophic candidiasis (leucoplakia-like lesions which do not scrape off but respond to antifungal treatment) and angular cheilitis may also be present.

45

Oral CandidiasisClinical Types

Erythematous Pseudomembranous Angular Cheilitis

46

• Esophageal infection may coexist.

• Up to 80% of patients with pain on swallowing have Candida esophagitis with pseudo membranous plaques visible on barium swallow and endoscopy .

• The pain is usually associated with dysphagia and, when untreated, leads to weight loss.

47

48

ORAL HAIRY LEUCOPLAKIA:

• Appears as white plaques running vertically on the sides of the tongue.

• EBV is implicated as the causative factor.

• Usually asymptomatic and doesn’t require any treatment.

49

50

GASTROINTESTINAL DISEASES

• Pain on swallowing, weight loss and chronic diarrhoea are common in the later stage of HIV infection.

• A range of opportunistic infections and tumours are also responsible for these symptoms.

51

CYTOMEGALOVIRUS:

• Is only seen if the CD4+ count is less than 100/µL.

• Mainly affects the esophagus but may involve the whole of the GIT.

• Presents as gradual onset of localized pain on swallowing, retrosternal pain, dysphagia, fever , weight loss, watery diarrhoea accompanied with blood and colicky abdominal pain.

• Diagnosed by endoscopy, blood investigations and tissue biopsy.

52

CRYPTOSPORIDIUM AND MICROSPORIDIUM:

• These are contagious zoonotic protozoal enteric pathogens.

• They account for 20% of the cases of diarrhoea in HIV infected individuals.

• Present as acute or sub acute onset of large volume watery stools, vomiting and weight loss.

• Diagnosed by stool sample examination.

• Other protozoal infections include isospora, cyclospora, cryptosporidium, Giardia and Entamoeba hystolytica.

53

LIVER DISEASEHEPATITIS B:• Majority of HIV infection individuals show evidence

of HBV exposure.• HBV carriage rate depends on the mode of

acquisition, place of birth and ethnic group , immunization history.

• Although HBV co-infected patients have more aggressive disease, the immunosuppression seen in more advanced HIV affords some protection to the liver.

• Treatment with antivirals should be considered for all patients who have active viral replication or evidence of inflammation, fibrosis or scarring on biopsy.

54

HEPATITIS C

• Most patients with HCV acquire their infection from injection drug use .

• Only 15-20% of patients ever clear their initial infection.

• HIV treatment is usually initiated first to optimize the CD4 count to 350 cells/mm3.

• Because of interactions with ribavirin, some nucleotide reverse transcriptase inhibitors (ZDV, didanosine and possibly abacavir) should be avoided if HAART is being co-administered.

55

NERVOUS SYSTEM AND EYE DISEASES

• Diseases of the central and peripheral nervous system are common in HIV.

• This may be as a direct result of HIV infection or as an indirect result of CD4+ cell depletion.

56

TOXOPLASMA GONDII:

• Results in mild subclinical illness in immunocompromised with formation of latent tissue cysts which persist for life.

• Acquired from ingestion of food contaminated by cat feces or undercooked meat.

• Manifests when CD4+ cell count is below 100/µL.

• Presents with headache, fever, drowsiness, fits, and focal neurological signs, retinitis may coexist.

• MRI shows multiple ring enhanced lesions in cortical grey white matter.

57

58

PROGRESSIVE MULTOFOCAL LEUCOENCEPHALOPATHY

• Demyelinating disease caused by papavavirus.

• Occurs at very low cd4+ counts

• Presents with hemiperesis, visual/speech defects, altered mood,ataxia and seizures.

• Diagnosis by MRI, viral particle detection in the CSF.

59

PRIMARY CNS LYMPHOMA:

• These are high grade ,diffuse, B- cell lymphomas which occur in late stage HIV .

• History is 2-8 weeks of headaches focal features and sometimes confusion; seizures occur in 15% but fever is absent.

• Imaging demonstrates a large, single, homogeneously enhancing periventricular lesion with mild to moderate surrounding oedema and mass effect.

• Biopsy is definitive, but carries a small risk of morbidity.

60

61

HIV-ASSOCIATED ENCEPHALOPATHY

• HIV is a neurotropic virus and infects the CNS early during infection.

• Aseptic meningitis or encephalitis may occur at seroconversion, and minor cognitive defects such as mental slowness and poor memory may develop the disease progresses.

62

• Dementia occurs in late disease and is characterised by global deterioration of cognitive function, severe psychomotor retardation, paraparesis, ataxia, and urinary and faecal incontinence.

• Investigations show diffuse cerebral atrophy with widened sulci and enlarged ventricles on imaging, and a raised protein in the CSF.

63

64

CRYPTOCOCCOSIS :

• Caused by cryptococcus neoformans.

• At risk when CD4+ count is < 200/µL.

• Found in soil and spread through birds.

• Infection through inhalation with rapid spread to the meninges.

65

• Presents with headache, fever, drowsiness, confusion, photophobia, blurred vision and seizures. meningism and papilledema are usually absent.

• MRI shows meningeal enhancement with evidence of raised ICP with occasion masses in the Basal ganglia.

• Other tests are CSF analysis, blood investigations and urine and stool culture.

66

SPINAL CORD, NERVE ROOT AND PERIPHERAL NERVE DISEASE:

• Gullaian barre, transverse myelitis, facial palsy, brachial neuritis, polyradiculitis and peripheral neuropathy occur commonly in HIV infection.

• Vocuolar myelopathy is a slowly progressive myelitis resulting in paraparesis with no sensory level.

• Ataxia and incontinence occur in advanced cases.

• Hyperaesthesia, pain in the soles of the feet and paraesthesia, with diminished pin-prick, light touch and vibration sensation, and loss of ankle reflexes (75%) are typical. 67

• Polyradiculitis occurs in late-stage HIV (CD4 count < 50 cells/µL) and is nearly always a result of CMV.

• It causes rapidly progressive flaccid paraparesis, saddle anesthesia, absent reflexes and sphincter dysfunction.

68

RETINITIS:

• Usually caused by cytomegalovirus.

• At risk when CD4+ count < 50/µL.

• Causes necrosis and hemorrhage in the retina.

• Presents as sub acute history with flashing of lights, floaters, field defects and reduced visual acuity

• On fundoscopy well demarcated hemorrhagic exudates along the vessels and the periphery are seen.

69

70

PSYCHIATRIC DISEASE

• Anxiety and mood disturbance may be caused by pre-test issues such as worries about being infected and disclosure, receiving a positive result.

• Mild cognitive dysfunction is a common occurrence in later-stage disease and usually improves with HAART.

• Disorders of mental state may also result from drugs directly (e.g. depression with efavirenz) or indirectly .

71

DISEASES OF KIDNEY AND GENITOURINARY SYSTEM

• Due to direct consequence of HIV infection, due to oppurtunistic infection , neoplasms or due to drug toxicity.

• HIV associated nephropathy presents with proteinuria.

• Edema and hypertension are rare.

• Ultrasound examination shows enlarged and hyperechoic kidneys.

• Definitive diagnosis is by renal biopsy.

72

• Focal segmental glomerulosclerosis is seen in 80% , and mesangial proliferation in 10-15 % of the cases.

• Patients with HIV associated nephropathy should be treated for HIV infection regardless of the CD4+ cell count.

• Drug induced toxicity is due to pentamidine, amphotericin B ,adefovir,tenofovir and foscarnet.

• Cotrimoxazole may compete with tubular secretion of creatinine and cause its increase in the blood.

73

• Genitourinary tract infections are seen with a high frequency in patients with HIV infection,

• They present with dysuria, hematuria and pyuria. They may also present with skin lesions.

• Vulvovaginal candidiasis is a common problem in women with HIV infection.

• Symptoms include pruritis,discomfort, dyspareuniaand dysuria.

• Vulval infection presents as morbilliform rash that might extend upto the thighs.

• Vaginal infection presents with white discharge and plaques may be seen along an erythematous vaginal wall.

74

HAEMATOLOGICAL CONDITIONS

• All the three cell lines are affected by HIV.• Anaemia is caused by bone marrow infiltration

with oppurtunistic infections, neoplasms, bone marrow supression with drugs, as a direct affect of HIV, blood loss from Kaposi sarcoma or malabsorption as a result of a GI infection.

• Leucopenia results from bone marrow infiltration or due to drug toxicity.lymphopenia is a good marker of HIV.

• Thrombocytopenia occurs very early and may be the first indiactor of HIV in some cases.

75

CANCERS IN HIVAIDS-Defining Virus• Kaposi’s Sarcoma HHV-8• Non-Hodgkin’s Lymphoma EBV, HHV8• (systemic and CNS)• Invasive Cervical Carcinoma HPVNon-AIDS Defining• Anal Cancer HPV• Hodgkin’s Disease EBV• Leiomyosarcoma (pediatric) EBV• Squamous Carcinoma (oral) HPV • Merkel cell Carcinoma MCV• Hepatoma HBV, HCV

76

PATHOGENESIS

• Many are virally-induced cancers, but not all.

• Immune activation, inflammation and decreased immune surveillance.

• HIV may activate cellular genes or proto-oncogenes or inhibit tumor suppressor genes.

• HIV induces genetic instability.

• Increase susceptibility to effects of carcinogens

• Endothelial abnormalities may allow for cancer development.

77

KAPOSI SARCOMA• Appearance: Oral lesions appear as reddish

purple, raised or flat

• Size ranges from small to extensive.

• Behavior is unpredictable.

• Cutaneous lesions present as purple non pruriticpapules eapicially on the nose,legs and genitals and crease line distribution over the trunk.satellite lesion, brusing,locallymphadenopathy and edema are typical.

78

• Oral and GI tract lesion present as purple raised lesions at palate, gums, oesophagus, stomach and large bowel. Hepatospleenomegaly may be present.

• Pulmonary lesions present as breathlessness, cough,hemoptysis, chest pain and fever.

79

80

81

• Definitive diagnosis: biopsy and histological examination.

• No curative therapy-antiretroviral therapy, radiation treatment, chemotherapy and sclerosing agents have been, used to control oral lesions .

82

AIDS-RELATEDNON-HODGKIN’S LYMPHOMA

• Small noncleaved-cell lymphoma– Burkitt’s lymphoma and Burkitt-like lymphoma

• Immunoblastic lymphoma (primary CNS)• Diffuse large-cell lymphoma (90% CD20+)

– Large noncleaved-cell lymphoma– CD30+ anaplastic large B-cell lymphoma

• Plasmablastic lymphoma • Extranodal involvement

– Central nervous system, liver, bone marrow, gastrointestinal system.

83

84