Genital shedding of HIV in women with undetectable viral load: less of it, but still happening

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Antiretroviral treatment significantly reduced the frequency of genital shedding of HIV in women, according to a study conducted in Burkina Faso and published in the June edition of Sexually Transmitted Infections. But the investigators also found that HIV remained detectable in the genital tract of a significant proportion of individuals, even when they had an undetectable viral load in their blood.

All the women in the study were infected with the genital herpes virus HSV-2, and it is known that this can increase genital shedding of HIV. Nevertheless, the investigators believe that their study underlines the importance of providing safer sex information to patients taking anti-HIV drugs.

Access to antiretroviral therapy in Africa is increasing. Not only does HIV treatment improve the health and prognosis of HIV-positive individuals, but it can also have a public health benefit as well. This is because anti-HIV drugs can lower the amount of HIV in both blood and genital secretions. Although there is disagreement about whether or not a patient taking antiretroviral therapy with an undetectable viral load is infectious, there is a consensus that such treatment can, at the very least, reduce the risk of transmission of the virus.

Glossary

shedding

Viral shedding refers to the expulsion and release of virus progeny (offspring such as competent particles, virions, etc.) following replication. In HIV this process occurs in the semen, the vaginal secretions and other bodily fluids, making those fluids more infectious.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

safer sex

Sex in which the risk of HIV and STI transmission is reduced or is minimal. Describing this as ‘safer’ rather than ‘safe’ sex reflects the fact that some safer sex practices do not completely eliminate transmission risks. In the past, ‘safer sex’ primarily referred to the use of condoms during penetrative sex, as well as being sexual in non-penetrative ways. Modern definitions should also include the use of PrEP and the HIV-positive partner having an undetectable viral load. However, some people do continue to use the term as a synonym for condom use.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Studies in a number of settings have looked at the impact of antiretroviral therapy on genital shedding of HIV in women. But the studies conducted in Africa have often had a cross-sectional or “snap-shot” design. This means that it has not been possible to determine the longer-term impact of anti-HIV drugs on shedding of HIV in the genital tract.

Researchers therefore collected blood samples and cervico-vaginal swabs from 39 women starting HIV treatment for the first time in Burkina Faso. All the women were also infected with HSV-2 and were participating in a study to see if treatment with the anti-herpes drug valaciclovir had an effect on HIV replication.

HIV treatment consisted of AZT (zidovudine, Retrovir) or d4T (stavudine, Zerit) with 3TC (lamivudine, Epivir) and efavirenz (Sustiva). The study participants had blood and cervico-vaginal samples taken after 18 weeks of HIV treatment and then every two weeks until week 28.

On entry to the study, median CD4 cell count was 103 cells/mm3 with median viral load in the blood being 61,000 copies/ml. All the women were screened for sexually transmitted infections and provided with appropriate treatment if necessary.

After 18 weeks of antiretroviral therapy, only one woman had detectable HIV in her blood, with two (5%) having HIV detectable in their cervico-vaginal swab. Median CD4 cell count had increased to 215 cells/mm3 at this time.

At the final follow-up visit, five women (13%) had detectable HIV in their blood, with six (13%) having evidence of genital HIV shedding.

Overall, HIV was present in 13% of the cervico-vaginal samples with 19 of the 39 women having genital shedding of HIV at least once. Even when the investigators restricted their analysis to the 34 women who had an undetectable viral load in their blood at every visit, they found that 16 (47%) had detectable HIV in their cervico-vaginal swabs at least once. The researchers calculated that HIV was detectable in 10% of genital samples obtained when women had an undetectable viral load in their blood.

But even when HIV was present in the genital compartment, the investigators’ research showed that it was 6.8-fold lower than before HIV treatment was started.

“Virological suppression at the systemic level was accompanied by a marked reduction in the frequency of HIV genital shedding, and a near sevenfold decrease in the quantity of HIV-1 RNA when genital shedding was measured”, write the investigators.

But they note that the frequency of genital shedding was higher than that seen in some other African and western studies. They believe that their study shows the importance of measuring genital secretions of HIV at a number of time points rather than relying on a single “snap-shot.”

Coinfection with HSV-2, daily vaginal douching, and the poor penetration of drugs such as d4T and efavirenz into the genital tract could, the investigators suggest, be possible reasons for the high proportion of women with evidence of HIV in their genital tract despite having a good response to HIV treatment.

They also note that it has yet to be shown if HIV present in genital secretions during effective HIV treatment is infectious.

Although reduced genital shedding of HIV can reduce the risk of HIV transmission, the investigators conclude that the findings of their study “underscores the importance of continued education regarding safe sex messages and the correct use of condoms for patients taking HAART.”

References

Nagot N. et al. Longitudinal effect following initiation of highly active antiretroviral therapy on plasma and cervico-vaginal HIV-1 RNA among women in Burkina Faso. Sex Transm Infect 84: 167 – 70, 2008.

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