HIV: Make the diagnosis and take the next step

During replication and transmission of HIV (green), RNA is converted to DNA.
During replication and transmission of HIV (green), RNA is converted to DNA.

The CDC estimates that with more than 40,000 new infections annually, more than 1.2 million people in the United States are living with HIV—and 24% to 27% may not be aware of their infection status.1 Studies have shown that HIV is often diagnosed late in the disease process, when the individual has already developed AIDS, which typically occurs 8 to 11 years after HIV infection.2 Research also points to missed opportunities to offer HIV testing and diagnose the infection before AIDS develops, which would enable the newly diagnosed individuals to employ precautions to protect their partners from becoming infected.3,4 Almost half of HIV transmissions studied by Brenner et al were attributed to transmission by newly infected persons.5

In response to these issues, the CDC put forth revised recommendations for HIV testing that encourage screening for patients in all health-care settings after the person is notified that testing will be performed, unless he or she declines (opt-out screening).4 Primary-care providers need a better understanding of trends in HIV infection and what to do when an HIV test is positive. In a recent survey of 1,165 primary-care providers, 54% of the respondents reported treating HIV-positive individuals, with 43% indicating an "increased" or a "dramatically increased" caseload over the past year.6

HIV viral dynamics

HIV is classified as a retrovirus that is completely dependent on CD4 T cells for copying and surviving. The virus enters the CD4 T cell by binding onto receptors and fusing with the lipid outer layer. The virus then converts its ribonucleic acid (RNA) to deoxyribonucleic acid (DNA) through the enzyme reverse transcriptase. The enzyme integrase helps the virus to become part of the human DNA in the cell's nucleus. During transcription and translation, enzymes assist the HIV genes by converting them into messenger RNA, which then leaves the nucleus with the HIV codes within. The enzyme protease makes smaller pieces of the long strands of protein; these pieces become mature viral cores. The new virions bud from the CD4 T cell and go on to infect other cells and repeat the process. HIV can replicate itself billions of times each day.

Signs and symptoms of HIV infection

Acute retroviral syndrome (ARS) occurs early in the new infection. Approximately 50%-70 % of HIV-positive persons will experience an influenzalike illness that may consist of one symptom or a constellation of symptoms including fever, rash, pharyngitis, lymphadenopathy, and myalgias. Because these symptoms are nonspecific and frequently resolve on their own, without a high index of suspicion clinicians may not consider HIV infection in the differential diagnosis. An exposed individual usually becomes symptomatic two to four weeks after transmission and will have a markedly high HIV viral load (amount of virus in the serum).

The asymptomatic period of HIV infection can last from a few months to up to 15 years. This varies from person to person and is usually associated with the level of HIV viral load—typically, those with higher viral loads deteriorate faster than those with lower loads. During this time, the CD4 T cells usually decline at an average rate of approximately 50 cells/µL/year. The CDC defines AIDS as persons with both documented HIV infection and CD4 T cells <200/mm3 whether other AIDS-defining conditions are present or not, or the presence of an AIDS-defining condition (Table 1).

Many patients will be asymptomatic during the clinical latency period, but various nonspecific findings on physical examination and in lab tests are associated with HIV. Generalized nontender lymphadenopathy involving the cervical, occipital, and/or axillary nodal chains is very common and can persist beyond primary infection. The presence of unexplained fevers, weight loss, night sweats, dementia, and neuropathy help rule in HIV infection. Skin lesions may be suggestive of HIV infection. Seborreahic dermatitis, psoriasis, molluscum contagiousum, and extensive condyloma are all diagnoses associated with HIV infection. Oral candidiasis (thrush) and oral hairy leukoplakia may be seen when CD4 T cells fall to less than 500/mm3. Recurrent or severe herpetic lesions and chronic vaginal candidiasis should prompt consideration of HIV testing. Unexplained anemia, neutropenia, leukopenia, and an elevated protein level are all commonly seen laboratory abnormalities caused by HIV infection.

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