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Chapter: Medical Immunology: AIDS and Other Acquired Immunodeficiency Diseases

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Clinical Stages of HIV Infection

When the infection is left to follow its natural course, most HIV-infected patients will develop AIDS.

Clinical Stages of HIV Infection

When the infection is left to follow its natural course, most HIV-infected patients will develop AIDS. The asymptomatic period that precedes the diagnosis of AIDS may extend for several years, and the onset of clinical manifestations of AIDS may be gradual or abrupt. Many alternative classifications of the clinical stages of HIV-induced disease have been proposed, one of which is as follows:

·              Acute retroviral infection (usually a mononucleosis-like syndrome)

·              Asymptomatic (no symptoms with the exception of the presence of lymphadenopathy) Early symptomatic (non–life-threatening infections, chronic or intermittent symp- toms)

·              Late symptomatic (increasingly severe symptoms; life-threatening infections; malig-nancies)

·              Advanced (high frequency of “opportunistic infections”; increased death risk)

1. Acute Illness Associated with Seroconversion


The typical incubation time is estimated to be 2– 4 weeks between exposure and onset of symptoms. Viremia occurs at that time and virus transmission can take place before an-tibodies are detected. The clinical picture is similar to infectious mononucleosis or flu-like. Fever, sore throat, myalgias, headache, malaise, and a maculopapular rash are the most predominant symptoms. Although these symptoms may be rather frequent (it is es-timated that 53–93% of patients present them), their lack of specificity leads to frequent misdiagnoses on the part of both the patient and the physician. Most patients recover completely from the acute infection, although in some headaches and adenopathy may persist.

The results of enzymoimmunoassays for HIV antibody during this stage are often negative. Seroconversion usually occurs 6 weeks after infection (antibodies to gp120 and gp41 are usually detected first, followed by antibodies to p24). Thus, if a patient sus-pected of being infected with HIV is seronegative, but definitely classified as belonging to a high-risk group, the serological studies should be repeated after 6 additional weeks. In rare cases, seroconversion can be significantly delayed (sometimes for one year or longer).

With the availability of highly effective therapy, there is a strong current of opin-ion emphasizing the need for early diagnosis so that therapy can be instituted well before the immune system is affected by the infection. Rapid diagnosis of HIV infection can be best achieved by detection of viral RNA by PCR. This is also the best available approach to diagnosis in a child born from an HIV+ mother, because the child may be falsely pos-itive in serological assays for several months due to the transplacental transfer of mater-nal antibody.

2. Asymptomatic Infection


The patient remains seropositive with minimal or no symptoms (diffuse reactive lym-phadenopathy and headache may be present at this stage) for variable periods of time (9–11 years on average, probably 20 years in some individuals). Considerable interest has been focused on the study of laboratory parameters that may be associated with the progression of HIV-infected individuals towards clinically significant immunodeficiency The determi-nation of the viral load is considered the most reliable parameter for prognostic evaluation of any given patient. The CD4 count should also be followed closely, as an index of the de-gree of immunocompromise.

It is important at this asymptomatic stage to evaluate the patient for other diseases that may be seen in HIV-infected patients, such as syphilis, hepatitis B, and tuberculosis, and treat any such condition that may be diagnosed. Prophylactic measures to avoid infec-tions known to occur with increased frequency in HIV+ patients are also indicated:

·              Chemoprophylaxis of tuberculosis with Isoniazid and immunoprophylaxis of in-fluenza and pneumococcal pneumonia.

·              Toxoplasma serology is also recommended, since it may help screen the patients at risk for developing severe toxoplasmosis at later stages of the disease. Eight to 16% of HIV-infected individuals in urban areas have serological evidence of infection with Toxoplasma gondii; of those, 30–50% will develop toxoplas-mosis as their degree of immunosuppression increases, the percentage rising to 80% when CD4 counts drop consistently below 100/mm3.

·              In HIV+ females, biannual PAP smears are recommended due to increased frequency of infection with papillomaviruses, which in turn is related to the development of cervical carcinoma.

3. Early Symptomatic HIV Infection


Fever, night sweats, fatigue, chronic diarrhea, and headache in the absence of any specific opportunistic disease in a previously asymptomatic HIV+ patient mark the transition to-wards symptomatic disease. Diarrhea in these patients is most likely due to direct infection of the GI mucosa by the HIV virus. Disseminated lymphadenopathy, believed to represent a reactive response of all the nodal elements, is prominent in some patients and less obvi-ous in others. Both T- and B-cell populations are expanded, and virus is not present in the reactive B lymphocytes.

Mucosal candidiasis is a frequent presenting symptom. In adult men, oral candidia-sis is very rare other than in HIV-positive patients. In HIV-positive women, recurrent vagi-nal candidiasis is a frequent cause for seeking medical attention.

Kaposi’s sarcoma may also be a relatively early presentation. It is caused by a virus of the herpes family (human herpesvirus 8, HHV-8). Infections with this virus in HIV+ pa-tients seems to be associated with exaggerated release of IL-6, IL-1, TNF, and oncostatin M by activated macrophages, which would act synergistically in promoting the develop-ment of the vascular proliferative lesions typical of the tumor.

With time, anergy and other laboratory evidence of immunodeficiency may develop, and some opportunistic infections may start affecting these patients, particularly recurrent mucosal candidiasis, oral leukoplakia (often asymptomatic), upper and lower respiratory tract infections, and periodontal disease.

4. Late Symptomatic and Advanced HIV Disease


With the progressive decline of CD4+ counts, the risk for development of opportunistic in-fections increases. The onset of opportunistic infections is considered as the clinical hall-mark for diagnosis of full-blown AIDS.

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