The stages and natural history of HIV infection

Last literature review version 18.3: Thu Sep 30 00:00:00 GMT 2010 | This topic ‎last updated: Thu Sep 23 00:00:00 GMT 2010 (More) ‎
INTRODUCTION — The human immunodeficiency virus (HIV) pandemic has spread ‎to every country in the world and has infected 59 million persons worldwide, ‎including 20 million who have already died [1]. (See "The global human ‎immunodeficiency virus pandemic".)‎
An estimated 1.1 million persons in the United States have been infected with HIV; ‎at the end of 2003, approximately 405,926 persons were living with AIDS. The ‎number of reported cases in 2003 was essentially the same as the number in 1999 ‎‎[2]. This trend follows a period of sharp decline in reported cases after the ‎introduction of HAART.‎
HISTORICAL PERSPECTIVE — Since the original description in 1981 of an unusual ‎cluster of cases of Pneumocystis carinii pneumonia and Kaposi's sarcoma in ‎previously healthy homosexual males, substantial advances in our understanding of ‎the acquired immune deficiency syndrome (AIDS) have been achieved. The ‎identification of a cytopathic retrovirus in 1983 and development of a diagnostic ‎serologic test for HIV-1 in 1985 have served as the basis for developing ‎improvements in diagnosis.‎
In addition, therapy was dramatically altered with the introduction of antiretroviral ‎drugs in 1987 and revolutionized by combination treatment, known as highly active ‎antiretroviral therapy (HAART), in 1996. In the three years following the introduction ‎of HAART, mortality, AIDS, AIDS-defining diagnoses, and hospitalizations all ‎decreased 60 to 80 percent. The EuroSIDA study, comparing this early HAART period ‎to pre-HAART and later HAART (1998 to 2002) treatment periods, found a sustained ‎decrease in mortality and progression to AIDS with ongoing HAART [3]. Despite the ‎absence of a cure, the natural history of the disease was radically changed [4].‎
Despite these advances, it is still useful to review the natural history of HIV infection ‎without antiretroviral therapy and the classification of disease. Although modified ‎from the initial case definition, the newer Centers for Disease Control and Prevention ‎‎(CDC) classification system remains the cornerstone for diagnosing HIV and AIDS.‎
STAGES OF HIV-1 INFECTION — HIV-1 infection is divided into the following ‎stages:‎
•    Viral transmission ‎
•    Primary HIV infection (also called acute HIV infection or acute seroconversion ‎syndrome) ‎
•    Seroconversion ‎
•    Clinical latent period with or without persistent generalized lymphadenopathy ‎‎(PGL) ‎
•    Early symptomatic HIV infection (previously known as "AIDS-related complex" ‎or ARC and more recently referred to as Class B according to the 1993 CDC ‎classification) ‎
•    AIDS (AIDS indicator condition according to the 1987 CDC criteria and revised ‎‎1993 CDC criteria that include a CD4 cell count below 200/mm3 regardless of ‎the presence or absence of symptoms) ‎
•    Advanced HIV infection characterized by a CD4 cell count below 50/mm3‎
VIRAL TRANSMISSION — HIV infection is usually acquired through sexual ‎intercourse, exposure to contaminated blood, or perinatal transmission. The mode of ‎acquiring HIV infection was undetermined in 4 percent of the cases originally ‎reported to the CDC. A careful review of 32,497 cases, however, revealed that only ‎‎0.2 percent had no clearly defined risk factor. (See "Transfusion transmitted HIV ‎infection and AIDS".)‎
Mode of acquisition — The distribution of the modes of transmission of HIV ‎infection varies in different countries. In resource-limited areas, vaginal sex is ‎responsible for 70 to 80 percent of AIDS cases and perinatal transmission and ‎injection drug use (IDU) for 5 to 10 percent each [5]. In contrast, during the first 25 ‎years of the epidemic in the United States, male-to-male sexual contact and IDU ‎accounted for about one-half of cases .‎
The relative contribution of different routes of transmission has varied over time in ‎the United States as reported by the CDC:‎
•    The estimated number of AIDS cases remained relatively stable, but the ‎number of cases among men who have sex with men (MSM) and heterosexual ‎adults and adolescents increased, while cases among injection drug users has ‎declined. ‎
•    Heterosexual transmission was the most commonly reported mode of HIV ‎acquisition among women. ‎
•    A follow-up survey for 2008 of 33 states found that 54 percent of new HIV ‎diagnoses were among MSM, which represented an increase of 16.6 percent ‎from 2001 to 2008; declines in case finding were seen concurrently in other ‎risk groups (eg, high-risk heterosexuals and injection drug users) .‎