Introduction

Definition and Causes

Human immunodeficiency virus (HIV) is a retrovirus that targets primarily CD4+ T helper cells. Depletion of CD4+ T cells causes progressive immunologic decline and when CD4+ T cell counts fall below 200 cells/mm3 opportunistic infections occur and an infected patient is described as having acquired immunodeficiency syndrome (AIDS).

Epidemiology

At the end of 2011, an estimated 1.2 million people ≥13 years of age in the United States were living with HIV. Of those living with HIV, approximately 14% were undiagnosed and persons aged 13 to 24 years accounted for over half of the undiagnosed cases. The Centers for Disease Control and Prevention (CDC) estimates that from 2007 to 2011 the number of persons infected with HIV increased by 7.2% with the highest prevalence of infection among individuals 45 to 54 years of age (954/100,000 population).1

Males account for the majority (76.7%) of diagnosed and undiagnosed Americans living with HIV. In males diagnosed with HIV, most (70.3%) acquired infection via male-to-male sexual contact. This differs from males with undiagnosed infection, in whom the highest percentage of infection (19.1%) is attributed to heterosexual contact.1

The global HIV/AIDS epidemic vastly exceeds what is seen in the US. At the end of 2012, approximately 35.3 million people worldwide were living with HIV. The epidemic continues to disproportionately affect sub-Saharan Africa, which accounted for approximately 70% of all new HIV infections in 2012.2

Pathophysiology and Natural History

Human immunodeficiency virus infection was first described in 1981 when an epidemic of Pneumocystis jiroveci (formerly identified as Pneumocystis carinii) pneumonia was noted in homosexual men.3 In 1984, HIV was identified as the causative agent of AIDS.

The human immunodeficiency viruses belong to the lentivirus subfamily of the RNA retroviruses. Like most retroviruses, the HIV genome consists of three structural genes:

• gag codes for viral capsid proteins;
• env codes for viral envelope proteins; and
• pol codes for proteins responsible for viral replication, including the RNA-dependent DNA polymerase known as reverse transcriptase.

In addition, several other regulatory genes are present, including nef, rev, and tat.

Most commonly, transmission of the virus occurs after a breach in the integument or mucous membranes. Human immunodeficiency virus infection occurs when the viral envelope subunit gp120 binds to the human CD4+ T cell receptor found primarily on lymphocytes and monocyte-derived macrophages. In addition, binding also requires the presence on the host cell of the chemokine receptor CCR5 or CXCR4. The viral envelope then fuses with the host cell, allowing release of the viral core into the host cell. Viral DNA is synthesized by reverse transcriptase and incorporated into the host genome by the protein integrase. Once the viral gene products are transcribed and assembled, the HIV protease mediates packaging of new virions for release into serum to propagate the infection.4

Over time, infected persons have a progressive loss of CD4+ lymphocytes. In the early stages of infection, this may not be associated with clinical illness. The rate of CD4+ cell loss is variable and depends on viral and host factors. On average, infected persons lose 40 to 80 CD4+ cells/mm3/year.5 However, there is a subset of patients who tend to progress rapidly and another subset of patients (approximately 5%) who have little or no progression of clinical disease or decline in CD4+ counts over 10 years even without use of antiretroviral therapy (known as long-term nonprogressors).6

Risk of Transmission

The risk of HIV transmission depends on the exposure and degree of viremia of the source. Transmission occurs through contact with infected body fluids such as blood, semen, and vaginal fluid. The most common modes of transmission are sexual contact (male-to-male or heterosexual sex), parenteral exposure to blood and blood products, and vertical transmission during pregnancy. Factors that are thought to increase the risk of transmission include high viral load, concomitant sexually transmitted infections (STIs), and acute- and late-stage infection. Factors that decrease the risk of transmission include condom use, antiretroviral treatment, male circumcision, and preexposure prophylaxis.7

Risk of HIV transmission is highest from an infected blood transfusion and occurs at a rate of approximately 92.5% although this is now exceedingly rare given advancements in screening technologies and techniques.8 In terms of other parenteral exposures, needle-sharing during injection drug use confers an approximate 0.63% risk while exposure from a percutaneous (incidental needle stick) carries a 0.23% risk. Risk from receptive anal intercourse carries a 1.38% risk while insertive anal intercourse has a 0.11% risk. In terms of penile-vaginal intercourse, receptive intercourse confers a 0.08% risk and insertive intercourse carries a 0.04% risk. These rates of transmission are influenced by the factors listed previously that are thought to increase and decrease transmission risk.7 The risk of vertical transmission from mother to fetus without any preventive therapy is approximately 23%.8

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