Persistent generalized lymphadenopathy (PGL) (eDe Group III)

A subgroup of patients with asymptomatic HIV infection have PGL, defined as lymphadenopathy (>1 ern) at two or more extra-inguinal sites for more than 3 months in the absence of causes other than HIV infection. The nodes are usually symmetrical, firm, mobile and non-tender. There may be associated splenomegaly. The architecture of the nodes shows hyperplasia of the follicles and proliferation of the capillary endothelium. Biopsy is rarely indicated. Similar disease progression has been noted in asymptomatic patients with or without PGL. Nodes may  isappear with disease progression. The same laboratory markers as above are used to monitor patients. ‘USA definition also includes those with a CD4 count <200/mm3.

Symptomatic HIV infection (one Group IV)

Clinical evidence of progression of HIV infection is manifested by an array of symptoms and signs and CD4 cell counts decrease. Susceptibility to a range of opportunistic and conventional pathogens and tumours is increased as immunosuppression becomes more profound. Immunodeficiency leads to the following problems in clinical practice:
• Susceptibility to opportunistic infections and tumours
• Presence of multiple infections at one time
• Lack of typical signs and symptoms due to failure of the inflammatory response, e.g. cryptococcal meningitis commonly presents without signs of meningism and there may be no white cells present in the CSF These features mean that tissue or body fluid is required to directly identify infecting organisms.


Include general lassitude, weight loss, night sweats (often soaking the sheets) and diarrhoea. Such symptoms may be the earliest signs of major infections or malignancies or can be a direct result of HIV infection.
SKIN AND MUCOUS MEMBRANES are frequently the site of bacterial, fungal and viral infections. An intensely pruritic, papular eruption favouring the extremities may be found, particularly in patients from sub-Saharan Africa. Generalized dry, itchy, flaky skin is typical and hair may become thin and dry. Seborrhoeic dermatitis occurs on the face and trunk. Folliculitis, usually bacterial and often generalized, is common. Stomatitis, recurrent aphthous ulcers and gum disease may impair the patient’s ability to eat. Oral candidiasis is frequently extensive with associated angular cheilitis. In female patients recurrent severe vulvovaginal candidiasis may occur. Oral hairy leucoplakia is a sign of imrnuno-suppression first noted in HIV but now also recognized in other conditions. It appears intermittently on the lateral borders of the tongue or the buccal mucosa as a pale, ridged lesion. It is usually asymptomatic although patients may find it unsightly and occasionally painful. It shows a variable response to acyclovir. Aetiology is not clear but Epstein Barr virus (EBV) particles can be identified histologically. Labial and genital Herpes simplex virus (HSV) occur with increasing frequency and severity. Herpes zoster may occur in an atypical pattern, affecting more than one dermatome or becoming disseminated. Human papillomavirus (HPV) infection produces genital, planar and occasionally oral warts which may be slow to respond to therapy and recur repeatedly. The association of HPV with cervical and anal intraepithelial neoplasia in HIV -infected patients is still subject to scrutiny; however female patients should have cervical cytology on at least an annual basis. Molluscum contagiosum is very common appearing in atypical sites particularly on the face and around the eyes.


The mechanism for the causation of neurological dysfunction is not well understood but may result from direct infection of the glial cells and/or the effects of viral products on neurones. Loss of neurones and vacuolization occur in advanced nfection. Direct HIV pathology must be differentiated from opportunistic infections and tumours as the management strategies differ.
There may be a sensory polyneuropathy, ranging from mild paraesthesia to severe pain usually in the lower limbs. A progressive myelopathy can occur producing motor signs in the legs and sphincter disturbance. Autonomic neuropathy may be seen. Intellectual and cognitive impairment can occur, usually in the later stages of disease. The onset is usually insidious, with decrease in memory, poor concentration and personality change. Changes in affect are common and depressive or psychotic features can be present. Functional psychiatric disorders must be differentiated from organic disease. CT scan reveals varying degrees of atrophic change and EEG may give an encephalopathic picture.


Weight loss, diarrhoea and malabsorption are all common problems in chronic HIV infection. Anorexia, nausea and vomiting frequently complicate acute episodes of opportunistic infection and their therapy. An HIV enteropathy has been described but the exact role of HIV in the pathogenesis of diarrhoea and malabsorption is not clear.The major conditions affecting the gastrointestinal tract in HIV infection.


INFECTION. Anaemia, neutropenia and thrombocytopenia are all common in advanced HIV infection and may indicate underlying opportunistic infection or tumour, particularly if the patient is pancytopenic. All may be exacerbated iatrogenically.
1 Anaemia of chronic HIV infection is usually mild, normocytic and normochromic.
2 Neutropenia is common and usually mild.
3 Thrombocytopenia may be the only manifestation of HIV infection. Platelet counts are often moderately reduced, but may fall dramatically (10-20 x 109/litre) producing easy bruising and bleeding. The aetiology is unclear. Megakaryocytes are increased in the bone marrow but function may be impaired. Circulating antiplatelet antibodies may lead to peripheral destruction. Opportunistic disease in H IV infection As immunosuppression increases patients are susceptible to a wide range of infections and tumours. In an individual patient the clinical consequences of HIV -related immune dysfunction will depend on:

THROUGHOUT LIFE. Many of the clinical episodes represent reactivation of previously acquired infection which has been latent. Geographical factors are important in determining the microbial repertoire of an individual patient. Those organisms requiring intact cell-mediated immunity for their control are most likely to cause clinical problems.

Mucocutaneous manifestations of HIV infection.
Mucocutaneous manifestations of HIV infection.


High-grade pathogens such as M. tuberculosis, Candida and herpes viruses are clinically relevant even when immunosuppression is mild and will thus occur earlier in the course of disease. Susceptiblity to infections such as Pneumocystis carinii occur at later stages of immunodeficiency (usually when the CD4 cell count is less than 200/mm3)


When patients are severely imrnunocompromised (CD4 cell count <100/mm3), disseminated infections with organisms of very low pathogenicity, such as atypical mycobacteria and cryptosporidia occur. These infections are very resistant to treatment, not only because there are no good antimicrobial treatments available, but also because there is no functioning immune response. This hierarchy of infection allows for appropriate intervention with prophylactic drugs.
A summary of the infections in AIDS is given. The most important are described below.


Pneumocystis carinii

This organism most commonly causes pneumonia (PCP) ut can cause disseminated infection. The characteristic presenting features are persistent, non-productive cough, increasing shortness of breath, hypoxia and fever. The clinical features and investigation are discussed on Typically the chest X-ray shows a diffuse interstitial shadowing extending through the mid-zones bilaterally. In mild cases both the clinical examination and the chest X-ray may be within normal limits.

Major pathogens in HIV infection.
Major pathogens in HIV infection.

Treatment should be instituted as early as possible. The first line therapy is with high doses of co-trimoxazole orintravenous pentamidine for 21 days. In severe cases the addition of systemic corticosteroids has been shown to reduce mortality.
Recurrence is frequent but can be largely prevented by the use of low-dose co-trimoxazole (960 mg thrice weekly) or nebulized pentamidine (300 mg monthly). Prevention of PCP with the use of primary prophylaxis in HIV -infected patients known to be at risk of PCP (those with CD4 cell counts <200/mm3) has led to a marked reduction in incidence from around 50% to 5% in the UK. Although systemic prophylaxis is associated with a greater incidence of side-effects, nebulized pentamidine only protects the lungs and extrapulmonary pneumocystosis may occur in patients on this therapy.


Toxoplasma gondii most commonly causes encephalitis and cerebral abscesses in the context of AIDS, due usually to reactivation of previously acquired infection. Up to 45% of AIDS patients who have antibodies to T. gondii may still develop cerebral toxoplasmosis. Features of cerebral toxoplasmosis include focal neurological signs, convulsions, headache, multiple ring-enhancing lesions on CT scan, and positive IgG anti- Toxoplasma serology. The diagnosis is usually made on the basis of the CT or MRI brain scan. If there is doubt stereotactic brain biopsy can be performed.
Treatment is with pyrimethamine in combination with sulphonamide. Clindamycin and pyrimethamine may be used in sulphonarnide-sensitive patients. These regimens will control but not eradicate infection and thus lifelong maintenance is required to prevent relapse. Newer drugs are undergoing evaluation to eradicate the cysts of toxoplasmosis and potentially cure the infection.


Cryptosporidium parvum can cause a self-limiting acute diarrhoea in an immunocompetent individual. In HIV infection it can cause a severe and progressive watery diarrhoea which may be associated with anorexia, abdominal pain, nausea and vomiting. Cysts attach to the epithelium of the wall of small bowel causing secretion of fluid into the gut lumen and leading to failure of absorption. It is associated with sclerosing cholangitis. The cysts may be seen on stool specimens stained with Kinyoun acid fast stain. The organism can be easily seen on small bowel biopsy specimens.
Treatment is largely supportive as there are no effective antimicrobial agents available other than a nonabsorbable aminoglycoside, paromamycin, which may have a limited effect on diarrhoea.

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