| 2. Basic Principles
of HIV Infection |
page
288 |
HIV
is a human retrovirus that is acquired predominantly through contact of
infected body fluids with the bloodstream, a situation similar to the
transmission of hepatitis B virus. It mainly infects the CD4 population of
lymphocytes, which perform a helper cell function; immunodeficiency
develops as the number of CD4 lymphocytes decreases. Cell-mediated
immunity is mainly affected, but there is also impairment in the ability
to mount new B-cell-mediated responses. As a result, the patient becomes
susceptible to infections and neoplasms. Normal individuals usually have
approximately 600-800 x 106/mL CD4 lymphocytes. Patients with
HIV infection slowly lose their CD4 cells. Opportunistic infections and
neoplasms rarely occur until the number of CD4 lymphocytes drops below 300
x 106/mL. Certain infections are not seen until CD4 counts are
below 100 x 106/mL. HIV is also known to infect other cell
populations such as macrophages, nerve cells and possibly enterocytes,
where it may be clinically latent and act as a reservoir of virus.
Persons
recognized to be at high risk for acquiring HIV infection include
homosexual or bisexual men, intravenous drug users, hemophiliacs and
others who received blood or blood products prior to universal testing of
blood in approximately 1985. Heterosexuals who have unprotected
intercourse with infected partners are also at risk and at present
represent the group with the fastest-rising incidence of HIV infection in
North America. In Africa, where HIV infection is endemic, heterosexual
transmission through unprotected intercourse is the commonest mode of HIV
transmission. When seeing patients with suspected HIV infection, it is
important to get an accurate history of risk factors including sexual
orientation and practices, history of intravenous drug use, past exposure
to blood and blood products and travel to endemic areas.
Many
physicians find it difficult to discuss sexual orientation and sexual
practices with patients. It is often best to ask the patient directly
whether he or she is heterosexual, homosexual or bisexual. For male
patients the question can also be addressed by asking the patient if he
has ever had sexual relations with other men. Many persons may classify
themselves as heterosexual but may have had same-sex sexual experiences.
Sexual activity and practices should be ascertained by inquiring about the
number of sexual partners in the past and whether the patient has had anal
intercourse. Unprotected receptive anal intercourse represents the
highest-risk sexual practice for HIV transmission. A history of other
sexually transmitted diseases is also important as it suggests high-risk
activity, and the presence of open lesions during unprotected intercourse
may increase the risk of HIV transmission. It is important to address
these issues in a clinical and nonjudgmental way, as negatively phrased
questions or judgmental attitudes toward sexual orientation and practices
can interfere with the doctor-patient relationship. Patients who perceive
a judgmental or negative attitude are less likely to discuss these issues
truthfully with the physician.
The
acquired immunodeficiency syndrome (AIDS) results from infection with the
HIV and the resultant immunodeficiency. The diagnosis of AIDS is usually
made on the basis of demonstrating positive serology for HIV with the
presence of an opportunistic infection, neoplasm or a CD4 lymphocyte count
less than 200 x 106/mL. At present it appears that most
patients with HIV infection will eventually progress to AIDS; however, the
rate of progression is variable. It has been well documented that therapy
with antiretroviral drugs slows the progression of HIV infection to AIDS
and prolongs the life of patients with established AIDS. The common
antiretroviral drugs in use are the nucleoside reverse transcriptase
inhibitors zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC),
stavudine (d4T) and lamivudine (3TC). New drugs showing promise and
currently under evaluation include protease inhibitors (siquinavir,
ritonivir and indinavir) and the non-nucleoside reverse transcriptase
inhibitors. It appears that combination therapy with two or three
antiretroviral drugs is better than single-drug therapy and reduces the
incidence of drug resistance. Current recommendations for antiretroviral
therapy are that therapy with AZT alone or in combination should be
started once the CD4 lymphocyte count falls below 500 x 106/mL.
The best combination of antiretroviral drugs has yet to be determined.
With advancing immunosuppression, the common occurrence of certain
opportunistic infections such as Pneumocystis carinii pneumonia,
Mycobacterium avium-intracellulare and toxoplasmosis has also prompted
recommendations for prophylactic therapy. |