HIV Infection: Pathophysiology

HIV is an RNA retrovirus. It is unable to survive and replicate unless it is inside a living human cell. HIV destroys CD4+ T cells (also called helper T cells or CD4 + T lymphocytes), which play a critical role in the human immune response through recognition of infectious and neoplastic processes. The destruction of CD4 cells by HIV results in immune deficiency. The CD4 cell count is an indicator for immune function in those with HIV.

Normal CD4 counts range from 800 to 1200 cells/mm³. After initial infection, there is rapid viral replication, resulting in a high level of virus in peripheral blood (viral load). There is a corresponding drop in CD4 cells, which triggers an immune response, resulting in CD4 cell replacement and HIV antibody production. The viral load drops with establishment of immune response. Symptoms range from mild to severe (fever, fatigue, pharyngitis, myalgia or arthralgia, lymphadenopathy, headache, night sweats) in those recently infected with HIV and can be experienced 2 to 12 weeks after HIV exposure. This period is called acute retroviral syndrome, acute seroconversion syndrome, or primary HIV infection. Symptoms in this stage can often be mistaken by both patient and health care provider for a transient flulike illness. Consequently, few people are diagnosed during this time. Additionally, the time delay from infection to a positive HIV test result averages 10 to 14 days, but some do not seroconvert for 3 to 4 weeks. Almost all patients seroconvert within 6 months. This time delay between infection and positive test results is known as the window period. For this reason, patients who are at risk for HIV infection and test negative should be counseled to have the test repeated in 3 months (the close of the window period). If HIV is strongly suspected, an HIV RNA quantitative test can be done. A high viral load would support HIV diagnosis (>10,000 c/mL and usually >100,000 c/mL).

HIV Transmission

HIV is spread via intimate contact with blood, semen, vaginal fluids, and breast milk. Transmission of the virus occurs primarily by: (1) sexual contact (includes oral, vaginal, and anal sex); (2) direct blood contact (intravenous drug use with shared needles, shared drug works, shared contaminated personal care items such as razors, and blood transfusions [now extremely rare in the United States]); and (3) mother to child (through shared maternal-fetal blood circulation, by direct blood contact during delivery, or in breast milk). Included in these modes are accidental needle injury, artificial insemination with donated semen, and organ transplant. HIV is not spread by casual contact (e.g., hugging), by touching items previously touched by a person infected with the virus, or during participation in sports. Those at highest risk include persons engaging in unprotected sex, those with multiple sexual partners (either the patient themselves or partner[s] of the patient), intravenous drug users who share needles or drug works, and infants born to women with HIV. The risk of mother-to-child transmission (MTCT) is 25% without ART; the risk decreases to 1% to 2% with successful use of ART. Other factors that increase the risk of MTCT are mother with a viral load >1000 copies/mL at delivery, premature rupture of the membranes, hepatitis C virus co-infection, preterm gestation, and vaginal delivery.

Laboratory Testing

Several laboratory tests are important for initial patient evaluation upon entry to care, during follow-up evaluation for those not on ART, and before and after initiation or modification of ART to assess for immunologic and virologic efficacy of treatment.

The laboratory tests used to determine when to initiate medication therapy and to monitor efficacy of therapy and indications for changing therapy are CD4 T-cell count, plasma HIV RNA quantitative assay (or viral load [VL] test), and HIV resistance testing.

The count reflects the number of CD4 cells circulating in the blood. The result is listed as an absolute number and a relative percentage. The absolute count can vary in the same patient depending on laboratory used, time of day laboratory blood work is drawn, or acute illness. The CD4 percentage is a more stable reflection of the immune system and is used in conjunction with the absolute count to monitor health status and response to medication therapy. The patient should be encouraged to use the same laboratory at approximately the same time of day to promote consistency of results. The nurse should monitor the laboratory used, because lab value references vary from laboratory to laboratory. The HIV viral load is indicative of the level of virus circulating in the blood and is the best determinant of treatment efficacy. Two FDA-approved commercially available assays commonly used are the quantitative polymerase chain reaction assay and the branched-chain DNA. A key goal of therapy is to achieve and maintain a viral load below the limits of detection (<20 to 40 copies/mL, depending on assay used). This goal should be achieved in 16 to 24 weeks of therapy.

Classification

HIV disease staging and classification systems are important tools for tracking and monitoring the HIV epidemic and providing the clinician and patient with information about HIV disease stage and clinical management.

Treatment Goals

The primary goals for initiating ART are to reduce HIV-associated morbidity and mortality and prolong the duration and quality of life; restore and preserve immunologic function; maximally and durably suppress plasma HIV viral load; and prevent HIV transmission.

Indications for Antiretroviral Therapy

Classes of Antiretroviral Medications

Reverse transcriptase inhibitors, protease inhibitors (PIs), entry (fusion) inhibitors, CCR5 antagonists, and integrase inhibitors make up the classification of drugs known as antiretroviral therapy. Reverse transcriptase inhibitors (RT inhibitors) are further divided into nucleoside/nucleotide (NRTI) analogues and non-nucleoside (NNRTI) analogues. More than 20 different antiretroviral agents are FDA approved, and various agents are available in fixed-dose combinations that contain two or more HIV medications from one or more drug classes. PIs have changed the prognosis for millions of patients infected with HIV. PIs combined with RT inhibitors can reduce viral plasma levels to undetectable levels, offering significant clinical benefits.

The most recent additions include maraviroc (Selzentry) a CCR5 antagonist; raltegravir (Isentress) and dolutegravir (Tivicay), integrase inhibitors; and etravirine (Intelence) and rilpivirine (Edurant), nucleoside reverse transcriptase inhibitors.