Understanding the Sexual Transmission of HIV

How does sexual transmission happen and how can it be blocked by vaccines or microbicides?

Globally, 80% of the 40 million people now infected with HIV acquired the virus through sexual contact with an HIV infected partner. The vast majority of these infections occurred as a result of vaginal or anal sex without a condom (although there are extremely rare reports of HIV transmission through oral sex). It is important to remember that not all forms of intimate contact transmit HIV; the virus cannot be transmitted by kissing, hugging or holding hands.

When used correctly and consistently, male and female condoms are highly effective at preventing the transmission of HIV. More than half of the estimated 14,000 new infections every day worldwide occur in women, who often cannot negotiate condom use with their partners. Addressing social issues including poverty, gender stereotypes, women’s lack of education and autonomy can help prevent HIV infections. But there is also an urgent need for additional prevention strategies like vaccines and microbicides that could be used by both women and men to help protect themselves against HIV infection.

Condoms are a simple barrier method that work by preventing contact with bodily fluids containing HIV (semen or vaginal secretions). But blocking infection with a vaccine or a microbicide is a far more complicated task and both areas of research are now carefully studying the biology of sexual transmission.

Studying sexual transmission

Until relatively recently there was very little information about the early biological events in sexual transmission. This is because it is impossible to identify the exact time of HIV transmission and extremely difficult to study the tissues in the genital tract. Scientists have developed systems for studying these early events of sexual transmission. One system called the "cervical explant model" uses small pieces of human cervical tissue (obtained from healthy women undergoing hysterectomies) that can be maintained in a healthy state in a laboratory "culture" system. Scientists can also study the infection of various types of cells found in the genital tract. They also study early events of sexual transmission with SIV (the monkey version of HIV) in non-human primates.

Current understanding

Physical barriers and immune defenses

For someone to become infected during sexual contact, the virus must cross a physical barrier: either the skin covering the penis or the mucosal membrane lining the vagina and cervix. In addition to these physical barriers there are also mucosal immune defenses (including immune cells and antibodies) that work with the physical barriers to protect the body from foreign invaders, or "pathogens."

Together these defenses do provide some protection against HIV. We know this because HIV does not infect 100% of the people who are exposed to the virus during a single act of unprotected sex. Instead, the risk of transmission varies widely depending on many contributing factors, including the type of sexual contact (e.g., anal or vaginal sex), sexually transmitted infections (STIs) other than HIV, and the amount of virus in the semen or vaginal secretions of the infected partner. However it is very important to remember that no one can accurately estimate the likelihood of infection at any given time and that every sexual contact has the potential to transmit HIV infection.

Target cells

Sexual transmission starts when HIV infects immune cells in the genital tract or rectum. Much of the research on early events of sexual transmission focuses on the mucosal immune defenses, which include CD4+ T cells, dendritic cells (DCs), and macrophages. The surface of these cells is covered with molecules called "receptors" which allow the cells to interact with each other and with pathogens. HIV uses different receptors to enter these cells, including CD4 and CCR5 for T cells and DC-SIGN and mannose receptor for DCs. DCs in the genital tract can pick up HIV and carry it to the lymph nodes, which are hubs of immune activity in the body. Once HIV reaches the lymph node it rapidly infects CD4+ T cells and establishes "systemic" infection, meaning that the virus can be found in the blood and throughout the body.

Role of STIs and bacterial infections

Studies have found that people who are infected with STIs other than HIV (herpes, Chlamydia, gonorrhea, syphilis and others) are at greater risk for becoming infected with HIV. Also, people who are already infected with HIV and have other STIs and/or bacterial vaginosis often have high levels of HIV in their semen or vaginal secretions, and this may make them more infectious to their sexual partners.

There are several explanations for why these infections increase the risk of transmitting or acquiring HIV infection. Some STIs (e.g. herpes simplex virus type 2) can cause genital ulcers that make it much easier for the virus to cross the body’s physical barrier and reach its target cells. These infections also cause increased immune activity in the genital tract and various aspects of this may actually increase the risk of HIV infection. For example, some STIs can increase the number of activated CD4+ T cells that are key targets for HIV infection.

Diagnosing and treating STIs and bacterial infections in men and women—whether they are HIV-infected or -uninfected—is an important part of AIDS prevention.