HIV can be isolated from blood, semen, vaginal secretions, bone marrow, saliva, cerebrospinal fluid, tears, urine, amniotic fluid and breast milk. Transmission has been shown to take place only for blood, sexual secretions and breast milk. The low virus concentrations and the low isolation frequency from other body fluids may explain the absence of other transmission routes. In the year 2000, 90% of HIV transmission took place via heterosexual contact. There are no indications of the existence of other routes of transmission (such as food, water, blood-sucking insects, normal skin contact). The rate of HIV transmission through homosexual contact between men, intravenous drug use and haemophilia is much less significant in Africa than in Europe or the USA.

Transmission of the virus takes place through sexual (homosexual and heterosexual) intercourse. The risk of transfer per contact is approximately 0.3%, but is influenced by many factors. The presence of sexually transmitted diseases (STD) accompanied by ulcerations (syphilis, chancroid, herpes) increases the risk 5-fold. Hence the importance of treatment of other STDs in AIDS programmes. Transmission via oral sex has also been reported. Certain small groups ("core groups") such as prostitutes, truck drivers and military personnel, who are often away from home for long periods, have a disproportionate importance. These account for a substantial percentage of virus transfer. Having multiple sexual partners is a risk factor. This applies to several partners in the same period, as well as a number of consecutive partners spread over years. Seropositivity in prostitutes is very high in many countries. All too frequently people who know that they are HIV positive do not want to inform their partner.

Injections and medical procedures with non-sterile instruments (needles [including acupuncture needles], syringes, scalpels, endoscopes, dentistry material, etc.) are a second risk factor. The advice "do not recap needles" should be followed. Tattooing with contaminated needles as well as skin piercing can likewise be responsible for viral transmission. There is a 0.3% risk of becoming infected by needle stick injury with a contaminated needle. The risk of infection can be reduced 80% by promptly taking AZT after such an accident. This risk may be further reduced with HAART combination therapy (see post-exposure, prophylaxis, PEP).

Sharing needles and other materials used by intravenous drug users constitute a third risk factor. The importance of this transmission pathway varies greatly from country to country.

Blood transfusions form a fourth risk factor. In many countries blood that is used for transfusion has still not been sufficiently tested for HIV. Not only is there insufficient screening, but there is also still the problem of the "window phase". This is the time interval in which a person has been infected and is infectious, but does not yet have any detectable antibodies. Such persons are thus seronegative and yet infectious. Antigen can be detected in their blood. The more frequently AIDS occurs in the population, the greater the number of persons in the window phase. The injudicious use of blood should be discouraged as much as possible (also because of transmission of other infectious organisms). Patients with aplastic anaemia or with sickle cell anaemia who have to have repeated transfusions form a high-risk group. Blood should be regarded as a medicine with potentially very dangerous side-effects.

A fifth transmission pathway is from mother-to-child. A child born from a seropositive mother runs an approximately 25% to 33% risk of becoming infected at around birth (if no antivirals are taken). HIV has been isolated from breast milk. The chance of an HIV-infected mother passing on the virus to the child via breast-feeding is estimated to be 17%. HIV is not embryotoxic. It can be isolated from amniotic fluid, from the foetus after the 16^th week of pregnancy and from umbilical cord blood. HIV can obviously sometimes penetrate through the placenta and infect the foetus, though the percentage of children who are infected in the uterus is probably very low. There are strong indications that transmission often takes place at the moment of birth. Mothers in a very advanced stage of the disease, with low CD4 values and/or with a high viral load have a greater risk of transmitting the virus to their children. Mothers with vitamin A deficiency may have a higher risk. The virus usually cannot be detected in the baby’s blood immediately after birth, but only 4 to 8 weeks later. This corresponds with the primary viraemia and confirms that most infections take place during childbirth. Elective Caesarean section reduces the risk of transmission to the child. An important reduction of risk is to be expected if HAART is given. Caesarean section is of less advantage when the amniochorionic membranes have broken and/or the mother is already in labour.