Definition

HIV type 1 is a retrovirus that predominantly infects lymphocytes that bear the CD4 surface protein, as well as coreceptors belonging to the chemokine receptor family (CCR5 or CXCR4), which, if left untreated, can cause AIDS.

Classification

Diagnosis of AIDS by the Centers for Disease Control and Prevention (CDC) classification is made on the basis of CD4 cell count <200 cells/μL, CD4 percentage <14%, or development of one of the 25 AIDS-defining conditions.¹

Epidemiology

• HIV type 1 is common throughout the world. By the most recent estimates, over 38 million people worldwide are living with HIV or AIDS, with a significant burden of disease in sub-Saharan Africa.²
• In the United States, 1.2 million people are estimated to be infected with HIV with 14% of these people unaware of their infection. The CDC estimates there are nearly 40,000 new infections in the United States every year.
• Despite comprising only 14% of the population in the United States, African Americans account for nearly 42% of all new cases of HIV in this country. Hispanics are also disproportionately affected by HIV representing 27% of new HIV ­diagnoses. Women comprise approximately 19% of new HIV infections.³
• MSM remains the population most heavily affected by HIV in the United States. Of all new HIV infections in 2009, 69% were MSM.⁴
• HIV type 2 is endemic to regions in West Africa. It is characterized by much slower progression to AIDS and intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Pathophysiology

• After entering the host cell, viral RNA is reverse transcribed into DNA using the HIV reverse transcriptase. This viral DNA is inserted into the host genome through the activity of the viral integrase. The host cell machinery is then used to produce the relevant viral proteins, which are appropriately truncated by a viral protease. Infectious viral particles bud away to infect other CD4 lymphocytes.
• Most infected cells are killed by the host CD8 T-cell response.
• Long-lived latently infected cells persist, especially memory T cells.
• Infection usually leads to CD4 T-cell depletion and impaired cell-mediated immunity over a period of 8–10 years.
• Without treatment, >90% of infected patients will progress to AIDS, which is characterized by the development of opportunistic infections (OIs), wasting, and viral-associated malignancies.

Risk Factors

• The virus is primarily transmitted sexually but also via parenteral and perinatal exposure.
• The risk of transmission is low through blood transfusions (1 in 1.4 million). Sharing needles or needlestick injuries result in transmission in 50 per 10,000 exposures.
• Among sexual practices, unprotected anal receptive intercourse carries the highest risk of transmission (138 per 10,000 exposures), followed by insertive anal intercourse, vaginal receptive intercourse, and vaginal insertive intercourse. Oral intercourse carries a low risk of transmission.

Prevention

• HIV transmission can be prevented by multiple prevention methods including regular condom use (internal or external) for vaginal, oral, and anal intercourse, HIV pre- and postexposure prophylaxis, and needle and syringe programs.
• Postexposure prophylaxis (PEP), or the provision of antiretroviral therapy (ART) after needlestick injury or high-risk sexual exposure, can prevent infection. Regimens normally consist of two to three ART drugs taken over 28-day course.
• Preexposure prophylaxis (PrEP), or continuous ART in HIV-negative patients, has proven to decrease the rate of HIV transmission. The current guidelines recommend the use of PrEP for the following high-risk groups:⁵
  • MSM
  • Heterosexual HIV-discordant couples
  • Those with multiple sexual partners with inconsistent condom use
  • Commercial sex workers
  • IV drug users
  • A combination of emtricitabine–tenofovir disoproxil fumarate (TDF/FTC) was the first approved regimen for PrEP. Emtricitabine–tenofovir alafenamide (TAF/FTC) has been recently approved by the U.S. Food and Drug Administration (FDA) and has better renal and bone side effect profile. Before starting PrEP, it is essential to document a negative HIV test, no signs or symptoms of acute HIV infection, hepatitis B status (if positive, stopping PrEP can cause fulminant hepatitis and death), and normal renal function. These patients should be followed every 3 months for repeat HIV testing as well as STI screening, risk reduction counseling, and every 6 months monitoring of renal function.