How Genital Shedding Increases Risk of HIV Transmission

Transmission is possible even with undetectable virus

When you have HIV, viral shedding is the presence of the virus in semen or vaginal secretions (genital shedding), or in the mouth (oral shedding).

Viral shedding is reduced with HIV medication, but it can still occur even if you take your HIV treatment as prescribed—and viral shedding increases the risk of HIV transmission to an uninfected partner.

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How Genital Tract Shedding Occurs

Shedding refers to viral release from the host cell it has infected. Two of the ways this can happen are through processes known in the HIV life cycle as budding and apoptosis:

  • Budding: A stage where the virus scavenges components of the membrane from a cell it has infected to create its own outer shell. It can then bud from the host as a free-circulating virus.
  • Apoptosis: Also known as cell suicide, this is the process of cell death. With most infections, apoptosis destroys an invading virus along with the host cell itself. With HIV, however, the virus will force a cell into apoptosis in order to release its offspring (more copies of the HIV virus) into the body's circulation.

HIV shedding can occur in the genital tract but not in blood, where it might otherwise be fully undetectable. Evidence suggests that two factors may contribute to this: the variability of HIV within the cells of our body and the variability of HIV drug concentrations in different tissues of the body.

Genital Tract Shedding and HIV Variability

If you are using HIV therapy and taking your drugs as prescribed, you would think that your risk of passing the virus to others would be low, right? In most cases, you would be correct, but there are instances when the virus is present in secretions, especially if you have a high viral load in your blood.

One of the earliest revelations took place in 2000 when it was discovered that the strain of HIV can vary from one part of the body to the next. According to research from the long-standing Multicenter AIDS Cohort Study (MACS), some individuals with HIV were shown to have one genetic variation of the virus in their blood and another in their semen.

The study further looked into the patterns of shedding among research participants. In some cases, shedding was a continuous process occurring in both the blood and semen. In others, it was intermittent and took place primarily in the genital tract. In others still, there was no shedding at all.

What these findings suggested was that:

  • The variability of the HIV could translate to differing responses to therapy.
  • HIV shedding may be a condition to which a person is genetically predisposed.

The MACS investigators noted that in men with intermittent shedding, bacterial infections of the prostate gland were closely aligned with spikes in viral activity in semen. They hypothesized that localized inflammation of the prostate (the organ which produces semen) triggers shedding by activating dormant HIV viruses embedded in the cells of the prostate gland and seminal vesicles.

Subsequent studies have largely supported these findings and have shown that shedding can occur as a direct result of sexually transmitted infections (STIs), coexisting diseases, and even menstruation.

Effectiveness of HIV Drugs Can Vary in Blood, Tissues

We test blood for HIV because it offers the easiest access when compared to other samples, such as bone marrow or saliva. While blood is a strong measure of HIV viral load, it doesn’t necessarily provide the full picture of how effectively antiretroviral drugs penetrate different cells and tissues of the body.

For example:

  • Zidovudine (AZT) can infiltrate the brain and spinal cord more effectively and at higher concentrations than almost all other HIV drugs. This is why it had been long used in people with AIDS dementia complex as a means to slow progression of the disease. (Integrase inhibitors are now used to treat AIDS dementia complex.)
  • There is growing evidence Truvada, when used as a prevention therapy (known as PrEP), does not penetrate vaginal tissue in the same way that it does the rectum.

Research from the University of North Carolina at Chapel Hill showed that Truvada concentration in rectal tissue could offer upwards of 90% protection with only two to three PrEP doses per week. By contrast, the concentration of Truvada in vaginal tissue was far lower, providing only 70% protection even with near-perfect daily adherence.

Based on these facts, it is possible that HIV therapy can suppress the virus elsewhere in the body, but fall short in the genital tract if there is an infection—and the immune system could very well be the trigger that sparks shedding in both males and females.

How Your Immune System Triggers Shedding

The presence of any infection will activate the immune system. When this happens, the body responds by releasing substances in the body called cytokines which serve to signal and direct immune cells to the source of the infection.

While cytokines help fight disease, they can have a contradictory effect by promoting the release of dormant HIV hidden in various cells and tissues of the body. Known as latent reservoirs, these cellular havens effectively shield HIV from the body’s immune defenses. It is often during an acute illness, when the immune system is activated, that the virus will suddenly re-emerge. This is why some people can go for years without treatment and then suddenly have a major illness accompanied by an enormous spike in viral activity.

This pattern seems to apply to the genital tract shedding of HIV through the following steps:

  • In the presence of an infection like a sexually transmitted infection (STI) or prostatitis, the immune system will release a distinct array of proinflammatory cytokines.
  • When this happens, defensive white blood cells (leukocytes) will suddenly flood the site of infection.
  • The CD4 T-cell is a leukocyte that is the primary target of HIV.
  • As the T-cells become infected in the early attack, the viral numbers rise until the localized infection is brought under control.

It is during this burst of viral activity that a person who is using HIV treatment can potentially pass the virus to others. While the viral load may increase by only one log or so (jumping from, say, 100 to 1,000), it may still be enough to facilitate infection.

HIV Shedding During Menstruation

Genital shedding of HIV can occur as a result of menstruation. According to the researchers, viral shedding during menstruation could mean as much as a 65% increase in HIV risk if a woman is untreated.

A study from the Oregon Health and Science University (OSHU) investigated a group of women who were predisposed to genital shedding as a result of a coexisting herpes simplex (HSV-2) infection. HSV-2, a virus affecting 67% of the world’s population, is also known to cause vaginal shedding both in symptomatic and asymptomatic women.

Within this group of women, HIV shedding was common during menstruation with a nearly eight-fold increase in viral load compared to the premenstrual cycle. This happened whether a woman had symptoms of HSV-2 or not. While this increase may not represent much risk for women with suppressed viral activity, it was considered significant in those with higher viral loads.

A Word From Verywell

Since the introduction of PrEP, we’ve seen a measurable drop in the use of condoms. One French study, in fact, showed that the more consistently a person took PrEP, the less likely he or she would be to use condoms (54% less likely to be exact).

While the effectiveness of PrEP is doubtless, particularly in mixed-status couples and those who are at a high risk of infection, condoms remain an important part of HIV prevention.

Ultimately, any HIV infection is a result of multiple factors, including the type of sexual activity involved and the general health of the uninfected individual. Even if the viral load of the infected person is low, that risk of HIV transmission can be significant.

An undiagnosed STI paired with bacterial vaginosis paired with a nominal spike in viral activity is sometimes all it takes to turn a "low-risk" sexual activity into an opportunity for infection.

If in doubt about the risk of getting HIV from your sexual partner, or if you have multiple sexual partners, don’t take a chance. Use condoms and any other tools of prevention to protect yourself and your partner.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Bull M, Mitchell C, Soria J, et al. Genital shedding of human immunodeficiency virus type-1 (Hiv) when antiretroviral therapy suppresses hiv replication in the plasma. The Journal of Infectious Diseases. 2020;222(5):777-786. doi. 10.1093/infdis/jiaa169. Published August, 2020.

  2. Mehrbod P, Ande SR, Alizadeh J, et al. The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections. Virulence. 2019;10(1):376-413. doi. 10.1080/21505594.2019.1605803. Published December, 2019.

  3. Bull ME, Legard J, Tapia K, et al. Hiv-1 shedding from the female genital tract is associated with increased th1 cytokines/chemokines that maintain tissue homeostasis and proportions of cd8+foxp3+ t cells. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2014;67(4):357-364. doi. 10.1097/QAI.0000000000000336. Published December, 2014.

Additional Reading
  • Cottrell M, Yang K, Prince H, et al. Predicting effective Truvada PrEP dosing strategies with a novel PK–PD model incorporating tissue active metabolites and endogenous nucleotides (EN). HIV Research for Prevention Conference; Cape Town, South Africa; October 28-31 2014; oral abstract 22.06 LB.

  • Gupta P, Leroux C, Patterson B, et al. Human Immunodeficiency Virus Type 1 Shedding Pattern in Semen Correlates with the Compartmentalization of Viral Quasi-Species between Blood and Semen. Journal of Infectious Diseases. 2000;182:79-87.

  • Patel E, Kirkpatrick A, Grabowski M, et al. Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study. Clin Infect Dis. 2017;64(6):776-84.

  • Spencer L, Christiansen S, Wang C. Systemic Immune Activation and HIV Shedding in the Female Genital Tract. Journal of Acquired Immune Deficiency Syndromes. 2016;71(2):155-62.

  • Teyssier L, Suzan-Monti M, Castro D. PrEP and Condom Use in High-Risk MSM in the ANRS IPERGAY Trial. Conference on Retroviruses and Opportunistic Infections (CROI); Boston, Massachusetts; February 22-25, 2016; abstract 887.

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.