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Human Immunodeficiency Virus 1
(HIV-1) transmission

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Transmission pathways

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Sexual transmission

The most important route is sexual transmission, which contributes to 75% of HIV cases around the world. Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions.

It should be noted that epithelial mucosal cells, which line genitals do not get infected by HIV-1 directly. Rather, virus attacks T lymphocytes and dendritic cells that normally reside in submucosal layers in varied quantities (depending on inflammatory status of the tissue). The T lymphocytes and dendritic cells, in their turn, efficiently deliver virus to adjacent cells and also disseminate it throughout the body. Successful entry of single viral particle into a cell is sufficient for HIV-1 infection. Multitude of viruses in one patient occurs usually due to clonal reproduction of the mother virion. In high-risk subpopulations superinfections (infections with another viral strain) occur in 20% individuals.

The risk of acquiring HIV-1 from a single sexual contact varies widely and depends on donor' HIV-1 infectiousness and the recipient's susceptibility to HIV-1. Overall, the risk of HIV-1 transmission is low especially in comparison with other sexually transmitted infections (STIs). Usually a homogeneous, CCR5-tropic variant of HIV-1 is transmitted sexually to a new host. Although rare, transmission of a CXCR4-tropic variant can occur. Cell-free as well cell-associated virus is present in genital (vaginal and seminal) secretions and both are likely to be responsible for transmission. The intact thick epithelium of vagina, ectocervix, foreskin and rectum is interspersed with activated CD4 and CCR5 expressing cells and immature Langerhans cells, all susceptible to HIV-1 infection. It has been observed that inflammatory chemokine interleukin-6 (IL-6) enhances HIV- 1 transcription at ectocervix. Thus, it is likely that any natural or external factors (inflammation, microabrasions, ulcers, etc.) that increase the number of genital mucosal DCs or activated CD4+ T cells will increase the probability of HIV-1 acquisition after exposure.

Sexual transmission of HIV-1 in men who have sex with men (MSM) occurs by transcytosis through single columnar epithelial cell layer of the intestinal and rectal mucosa. Moreover, the relative fragility of the rectal mucosal epithelial layer may facilitate HIV-1 transmission.

Importance of donor's viral load

Data from studies of African heterosexual HIV-1-serodiscordant couples (a pair of long-term sexual partners in which one person is infected with STD and the other is not) identified that HIV-1 plasma viral load (VL) is the single most important determinant in predicting transmission. When plasma VL remains below 1,500 HIV-1 RNA copies/ml the risk of transmission is considered low. However the low plasma viral load as a proxy for genital shedding might be inaccurate. The virus can be detected in the genital tracts of up to 20% of men and women with undetectable VL due to HAART. Thus, although the risk of onward transmission of HIV-1 in the presence of a plasma VL <50 copies HIV-1 RNA copies/ml is very low it is not necessarily zero.

Sexual transmission studies - findings

The rate of HIV transmission per coital act was highest during early-stage infection

(Wawer MJ et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005 May 1;191(9):1403-9. )

The average rate of HIV transmission was:

In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission.

Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act

(Gray RH et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001 Apr 14;357(9263):1149-53. )

The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011. Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38,500 copies/mL or more, and were 0.0041 with genital ulceration versus 0.0011 without. Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner.

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Oral transmission

The risk of transmission of HIV through saliva of infected person via oral sex and kissing is very low for several reasons:

Higher risk of infection exists when infected semen contacts with oral mucosa. Ulcers in oral cavity or caries increase probability of infection further.

However, unlike genital and genito-anal sexual activities, the oral sex appears to be extremely uncommon transmission route.

One method to determine the risk of orally transmitting HIV is by studying serodiscordant couples who practice unprotected oral sex and are exposed to no other risks for infection. Thus, a 10-year (1989–2000) follow-up study was performed on 263 stable serodiscordant heterosexual couples whose only risk exposure was oral–genital contact without the use of a condom, with condoms being used for other sexual practices. Despite 10,295 active and 10,658 passive oral–genital contacts, no cases of seroconversion to HIV were found (del Romero J et al., AIDS. 2002).

Transmission of HIV-1 through bite

Deshpande AK et al. AIDS Res Ther. 2011; 8: 16. The potential risk of HIV-1 infection following human bite although epidemiologically insignificant, but it is biologically possible. There are anecdotal reports of HIV transmission by human bites particularly if saliva is mixed with blood. The oral tissues support HIV replication and may serve as a previously unrecognized HIV reservoir. The HIV infected individuals have more viruses in blood than saliva, possibly due to the potent HIV-inhibitory properties of saliva. The case presented here is of a primary HIV infections following a human bite where in the saliva was not blood stained but it got smeared on a raw nail bed of a recipient. The blood and saliva of the source and blood of the recipient showed a detectable viral load.

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Primary HIV-1 infection

Primary HIV-1 infection (PHI) represents the first 6 months after HIV-1 acquisition. This stage is characterized by very high plasma, oropharyngeal and genital tract viral load, which translates into a markedly enhanced risk of onward transmission to sexual partners. Moreover, there appear to be specific characteristics of recently transmitted viral variants that make them particularly infectious at a time when most individuals continue with high-risk sexual practices unaware of their changed HIV-1 status. For the majority of individuals such unchecked high level viral replication lasts approximately 3–5 months. A large study of heterosexual HIV-1 serodiscordant couples in Uganda showed that the probability of HIV-1 transmission per coital act was 8–10 times more likely in the first 5 months after HIV-1 acquisition and that PHI maybe up to 26 times more infectious than asymptomatic chronic disease. Mathematical models show that within populations with high rates of partner change PHI may contribute up to 31% of all new transmissions. In populations with slower rates of partner change the relative contribution of PHI becomes much less, constituting only about 9% of new transmissions.

Late stage of infection defined as the 6-35 months period prior to death was also associated with enhanced HIV-1 transmission.

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Other factors

Other sexually transmitted diseases (STDs) facilitate HIV-1 transmission by increasing both HIV-1 infectiousness and recipient's susceptibility. The strongest effect is associated with genital ulcer disease (GUD), gonorrhea, infectious syphilis and trichomoniasis.

There is possibility that hormonal contraception may increase infectiousness in HIV-1-infected women by increasing HIV-1 shedding in the genital tract and this is supported by studies of female primates treated with progesterone.

Clinical trials in South Africa, Kenya, and Uganda have shown that circumcision of HIV-1-negative adult males reduces their risk of acquiring HIV-1 infection through penile–vaginal sex by 60%. However, circumcision of HIV-1-infected men did not reduce HIV-1 transmission to female partners over 24 months.

All studies show that unprotected anal intercourse is more risky than vaginal sex and that receptive sex is riskier than active sex.

The use of Highly Active Anti-Retroviral Therapy (HAART) to limit viral replication in both plasma and genital tract secretions, is a logical method to reliably and durably limit transmission as well as treat the HIV-1 infected individual. HAART is already used in specific settings to reduce HIV-1 transmission chances during perinatal and postnatal exposure, and as pre-exposure prophylaxis. Successful HAART decreases HIV-1 infectiousness, but by increasing the life expectancy of infected individuals it increases the pool of potential transmitters. These two factors, decreased infectivity but increased duration of infectiousness, have opposing effects on transmission and may be further confounded by increases in risk behavior resulting from enhanced optimism concerning HIV-1 prognosis.

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Mother-to-child (vertical) transmission

Management of HIV-1 during pregnancy has improved so that vertical transmission is now limited to less than 2% of all cases.

The transmission can occur at three different times:

Successful viral suppression by achieving plasma HIV RNA viral load <50 copies/ml by the time of labor is the main aim of treatment of pregnant women. To reduce potential fetal anomalies, HAART is started after the first trimester. Women with undetectable plasma HIV RNA viral load at the time of labor can deliver vaginally as long as their labor is closely monitored. The babies of HIV-1 positive mothers need AZT prophylaxis. HIV-infected mothers should avoid breast-feeding.

Breast feeding is a major route of mother-to-child transmission of HIV (one third to one half of new infant infections worldwide). The highest rate has been observed in the first 3 months of life. Despite of great oral mucosal exposure to viruses, majority of infants, however, remain uninfected.

Because the mother's anti-HIV antibodies cross the placenta, infants of HIV-infected women will test positive with the standard HIV tests. Instead, they should be tested for plasma proviral HIV DNA until the third month of life. Infants tested negative at the third month of life are considered HIV negative. After 18 months of age, following the decay of their maternal antibodies, they also should test HIV negative by conventional assays.

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HIV at workplace

Of new HIV diagnoses during 2006 in the U.S., approximately 78% have occurred in persons aged 25 to 54, substantially impacting the American workplace. It was estimated that one in six large U.S. worksites (>50 employees) and one in 15 small U.S. worksites (<50 employees) have had an employee or employees with HIV infection or AIDS.

AIDS and HIV-1 infection are considered disabilities under the American with Disabilities Act (ADA) of 1990. The Act applies to all employers with at least 15 employees working at least 20 weeks in the current or preceding calendar year.

If an individual with HIV infection or AIDS is temporarily unable to perform the essential functions of the job, she/he may come under the protection of Family and Medical Leave Act (FMLA) of 1993.

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The HIV-Infected Health Care Worker

According to the U.S. Centers for Disease Control and Prevention (CDC), 57 health care workers have acquired HIV due to workplace exposures, representing a tiny fraction of the thousands of health care workers who are HIV-positive. Since the onset of the AIDS epidemic there were few instances in which health care workers transmitted HIV to patients. The first was a well-publicized case in which a Florida dentist transmitted HIV to six patients in his practice. Numerous serological surveys of patients treated by HIV-positive health care workers, including dentists, surgeons, obstetricians, and other physicians have revealed that transmissions of HIV from health care workers to patients are extremely rare. In contrast, hundreds of patients have become infected with hepatitis B following procedures by hepatitis B-infected health care workers. CDC has estimated that the risk for transmission of HIV or hepatitis B lies between 1/42,000 and 1/420,000.

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Literature

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