1. PHARMACOTHERAPY III PHCY 510
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY III
PHCY 510
Lecture 9-A Infectious Diseases “Human Immunodeficiency Virus Infection-Antiretroviral Therapy”-1 Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy, CPN University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
Describe transmission, etiology, clinical presentations and diagnosis and opportunistic infections in HIV infection,
Individualize the Anti retroviral treatments.

3. Infection with HIV (human immunodeficiency virus) leads to immunosuppression causing acquired immune deficiency syndrome (AIDS).
Transmission of Human Immunodeficiency Virus
Occurs through three primary modes:
sexual, parenteral, and perinatal.
Contact with infected blood or hazardous body fluids (Healthcare workers have a small risk of occupationally acquiring HIV, mostly through accidental injury, most often, percutaneous needlestick injury).

4. IV drug users, homosexuals, sexually transmitted diseases (STD’s) at high risk.
Condom use reduces the risk of transmission by approximately 20-fold.
Perinatal infection or vertical transmission from mother to infant (pediatric HIV).
Breast-feeding can also transmit HIV.
Although urine, tears, and saliva can contain HIV, transmission from these non bloody fluids is rare.

5. Etiology
HIV is a single-stranded RNA retrovirus that can be divided into types HIV-1 and HIV-2.
HIV-1 is the predominant infection found in the United States.
HIV-2 is found primarily in Africa.
Both types of HIV infection deplete the helper T-lymphocytes
(CD4 cell/mm3) and other cells of the immune system, including monocytes and macrophages, resulting in continued destruction of the immune system, and leading to the occurrence of opportunistic infections and malignancies.

6. Clinical Presentation of Primary HIV Infection in Adults
Clinical presentations of primary HIV infection vary, but patients often have a viral syndrome or mononucleosis-like illness with fever, pharyngitis, and adenopathy (lasts for 2 weeks).
Probability of progression to acquired immune deficiency syndrome (AIDS) is related to RNA viral load.

7. Diagnosis
Most commonly used screening method for HIV is an enzyme-linked immunosorbent assay, which detects antibodies against HIV-1.
False positives can occur in multiparous women;
in recent recipients of hepatitis B, HIV, influenza, or rabies vaccine;
following multiple blood transfusions;
in those with liver disease or renal failure, or undergoing chronic hemodialysis.
Positive enzyme-linked immunosorbent assays are repeated in duplicate and if one or both tests are reactive, a confirmatory test is performed for final diagnosis.
False negatives may
occur if the patient is newly infected and the test is performed before
antibody production is adequate. The minimum time to develop antibodies
is 3 to 4 weeks from initial exposure.

8. Western blot assay is the most commonly used confirmatory test.
The viral load test quantifies viremia (HIV RNA viral load or burden> 107 copies/mL)) by measuring the amount of viral RNA.
Viral load can be used as a prognostic factor to monitor disease progression and the effects of treatment.
The number of CD4 lymphocytes in the blood is a surrogate marker of disease progression.
The normal adult CD4 lymphocyte count ranges between 500 and 1,600 cells/ µL, or 40% to 70% of all lymphocytes.
The CD4 cell count is the best indicator of the extent of immune damage and risk of opportunistic infections.
Therefore, it is often used to determine if HAART should be started.

9. Persons with CD4 counts lower than 200 cells/mm or less than 14% of all lymphocytes are predisposed to a variety of opportunistic infections, including
Pneumocystis jirovecii (previously known as carinii) pneumonia.
As the CD4 counts drop below 50 cells/mm3, the prevalence of other infections increases including
Mycobacterium avium-intracellulare and Cytomegalovirus disease,

10. General Approach to Treatment of Human Immunodeficiency Virus Infection
Regular, periodic measurement of plasma HIV RNA levels and CD4 cell counts is necessary
This is to determine the risk of disease progression in an HIV infected individual and to determine when to initiate or modify antiretroviral treatment regimens.
Treatment decisions should be individualized by level of risk indicated by plasma HIV RNA levels and CD4 counts.
The most effective means to accomplish strong suppression of HIV replication is the simultaneous initiation of combinations of effective anti- HIV drugs with
drugs the patient has not been previously treated,
drugs that are not cross resistant with antiretroviral agents with which the patient has been treated previously.

11. Women should receive optimal antiretroviral therapy regardless of pregnancy status.
The same principles of antiretroviral therapy apply to both HIV infected children and adults,
HIV-infected persons, even those with viral loads below detectable limits, should be considered infectious.
They should be counseled to avoid sexual and drug-use behaviors that are associated with transmission or acquisition of HIV and other infectious pathogens.
Treatment is generally not recommended in persons with CD4 counts above 350 cells/mm3. Those between 201 and 350 cells/mm3 should be offered therapy.