The spread, treatment, and prevention of HIV-1: evolution of a global pandemic

Abstract

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference--male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.

Figure 1. Source of infections with HIV-1 by region.

An individual can become infected with HIV-1 from many sources, including contaminated blood and blood products (such as though medical injections, blood transfusions, and injection drug usage [IDU]), an infected mother transmitting the virus to her baby (before, during, or after birth and through breast milk), and through either vaginal or anal intercourse. The relative importance of a source of HIV-1 varies in different parts of the world. In some countries, infection with HIV-1 is mainly detected in specific groups at risk, including MSM, injecting drug users, sex workers, and the regular partners of such persons. In most countries of sub-Saharan Africa, however, HIV-1 is self-sustaining in the general population through heterosexual intercourse in HIV-serodiscordant couples. MTCT, mother-to-child transmission. The data presented here were mostly generated for 2005, but some data are from earlier years. Reproduced with permission from the Global HIV Prevention Working Group (103).

Figure 2. HIV-1 viremia and HIV-1 shedding over time.

The concentration of HIV-1 in blood and genital secretions varies dramatically depending on the stage of the disease. Shown here are data for HIV-1 viremia and HIV-1 shedding over time in men acutely or chronically infected with HIV-1. Measurements of HIV-1 RNA in blood plasma (gray) and seminal plasma (black) are displayed over 16 weeks. The data were generated from 16 acutely infected subjects, who contributed blood and semen at 60 and 34 time points, respectively, and from 25 chronically infected subjects, who contributed blood and semen at 123 and 89 time points, respectively. The highest viral loads were detected at the first time point after infection and in people with advanced disease. Boxes and whiskers denote the 25th and 75th quartiles and total range of values. Internal circles and horizontal lines represent mean and median, respectively. Reproduced with permission from AIDS (15).

Figure 3. Genomic maps of HIV-1 and HIV-2.

Although HIV-1 and 2 have similar genetic structures, the DNA sequences differ by up to 40%. Both viruses have structural and accessory genes that influence replication and pathogenesis (Table 1). Many of these are shared between the two viruses, such as gag and pol; however, only HIV-1 has a gene that encodes Vpu, and Vpx is only encoded by HIV-2. Reproduced from ref. .

Figure 4. Opportunities for preventing infection with HIV-1.

Prevention efforts can be divided into four broad categories: those offered to HIV-1–negative subjects, especially those in high-risk groups (e.g., the offer of male circumcision, condoms); those offered to people with a strong likelihood of recent exposure to HIV-1 (e.g., topical microbicides, antiretroviral preexposure prophylaxis [PrEP]); those offered shortly after exposure (e.g., postexposure prophylaxis [PEP]), and those offered to people who are already infected (secondary prevention; e.g., the use of antiretroviral therapy to reduce viral load).