Untangling HIV transmission in men

Study could put scientists on the right path [bonne voie] to blocking the spread of new infections.

Erika Check Hayden

Free-floating HIV particles in semen [sperme] may transmit the virus from one man to another.BSIP, CAVALLINI JAMES / SCIENCE PHOTO LIBRARY

HIV could be transmitted between men in the form of free-floating virus particles found in seminal fluid, rather than through HIV-infected cells found in semen.

The virus is known to be transmitted during sex through semen. But it has been difficult to study whether the virus's genetic material is transmitted in the form of infectious RNA virus particles or as DNA locked within infected cells in semen. The answer could determine which strategies are most useful for blocking transmission of the virus from one partner to another.

"We're very interested in how to interrupt transmission, and this tells us we should really focus on the RNA replicating at the time of transmission in the blood and genital tract," says infectious disease physician Davey Smith of the University of California, San Diego, who led the study.

Smith and his team analysed samples taken from six pairs of men. One member of each pair, the source, had infected the recipient partner with HIV. The researchers studied the genetic makeup of a portion of the virus in both the source and recipient members of the pairs, and in the semen from each source. They found that the viruses in the recipients were most genetically related to the free viruses found in the seminal fluid from the source.

However, the study is small, and some scientists have pointed out other caveats within its methods. But Smith notes that studies such as this have never been done before because it is difficult to detect HIV quickly after infection, and even more difficult to convince newly infected people to sign up for a HIV-research study. "It's a delicate situation to talk about HIV transmission, and even more delicate to start collecting these samples when someone is newly diagnosed," Smith says.

If borne out by additional studies, the latest work could support the idea of 'test and treat', which aims to reduce or prevent HIV transmission by administering antiretroviral drugs to people who are HIV-positive — thereby lowering the amount of virus found in their blood and bodily fluids, says Martin Stürmer of the Johann Wolfgang Goethe-University Hospital in Frankfurt, Germany, who was not involved with the study.

"These findings further support the prevention strategy that a suppressive antiretroviral therapy resulting in an undetectable virus load in the seminal plasma interrupts sexual HIV transmission," Stürmer adds.

The study could also promote the development of topical microbicides — some of which are currently being tested in clinical trials — that aim to block HIV from entering cells at the surface of the skin. "One of the big distractors from the whole microbicide movement has been that you could use antiretroviral drugs as microbicides, but if the virus is hiding out in cells in the form of DNA then your microbicide isn't going to block it," Smith says.

Antiretroviral drugs that are taken orally before HIV exposure — an approach known as pre-exposure prophylaxis, or PrEP, which is also being tested in clinical trials — are likely to be equally effective against viruses transmitted through cells or bodily fluids because these drugs aim to stop transmission by stopping viral replication. And the use of condoms would prevent transmission either through cells or through free virus.

In the blood?

Still, the work by Smith and his colleagues used too few participants to definitively answer the question of exactly how transmission occurs: "The number of cases in their study is small, thus a broad generalization of their findings is difficult," says Stürmer.

The results of the study would also be more convincing if the samples had been taken closer to the exact time of the recipient becoming infected, some researchers suggest, because HIV mutates rapidly.

The recipients in the study provided blood samples an average of 72 days after they believed they were infected, and the sources provided blood and semen samples around 90 days after infecting the recipients.

"The samples are never taken close enough" to the time of infection, says Ron Swanstrom at the University of North Carolina Chapel Hill Center for AIDS Research, who is also studying HIV transmission between sexual partners. "It's an inherent problem with working in this field," he says. "You're inserting yourself into these people's private lives and you do a lot of work for not many samples."

Swanstrom adds that the work of Smith and his colleagues does not address what happens in male-to-female transmission of HIV. In addition, because some of the source partners in the current study had themselves become infected only recently, the study could not rule out the possibility that they had transmitted the virus through their blood during intercourse rather than through semen, because the virus particles in the source blood and semen samples were genetically quite similar.

Stürmer points out that studies by other research groups, including his own², indicate that viral transmission can occur between sexual partners even when the HIV-positive partner is being treated successfully with antiretroviral drugs, and no virus is detectable in his blood. So although the paper supports the idea that the "test and treat" strategy should work, it does not guarantee that it will.

Smith says that his group hopes to address some of these questions by studying other pairs, by further investigating the virus's genetics and by asking more questions of the participants. "We hope to better characterize what's going on at the time of transmission, which means asking some difficult questions, such as what were the partners doing at the time of transmission? Were they using condoms or no condoms, and if not, why not?" Smith explains.

1. Butler, D. M. et al. Science Transl. Med. 3, 18re2 (2010).
2. Stürmer, M., Doerr, H. W., Berger, A. & Gute, P. Antivir. Ther. 13, 729-732 (2008).

http://www.nature.com/news/2010/100210/full/news.2010.62.html

Eprouver les battements de son coeur, les mouvements de sa respiration, sentir que son corps se réchauffe ou se refroidit : cette expérience de notre milieu interne, appelée intéroception, est à la base de nos émotions et constitue une part de notre conscience. Ces dernières années, plusieurs études d'IRM fonctionnelle ont suggéré que deux zones cérébrales jouaient un rôle essentiel dans cette perception de nos états physiologiques : l'insula, au centre du cerveau et le cortex cingulaire antérieur, situé plus en avant. Une équipe de neurologues américains, pilotée par Sahib Khalsa de l'université de l'Iowa, remet aujourd'hui en question cette théorie. Leurs travaux prouvent en effet qu'il est possible de percevoir nos sensations internes uniquement par la peau et les zones cérébrales associées au toucher, indépendamment de l’insula (1).

Pour le montrer, les neurologues se sont intéressés au cas de Roger, un patient dont l'insula et le cortex cingulaire antérieur ont été presque totalement détruits par un herpès encéphalique. Ils ont voulu savoir si ce sujet pouvait, malgré ses lésions, percevoir des variations de son rythme cardiaque. Ils lui ont donc administré, ainsi qu'à onze sujets témoins, un médicament qui accroît le rythme cardiaque, en augmentant progressivement les doses. Après chaque prise, les sujets devaient rapporter leurs sensations sur un carnet. Résultat : au fur et à mesure de l'expérience, Roger a senti son coeur s'accélérer, comme les sujets sains, et il s'est même révélé capable de décrire avec précision ses sensations.

D'où lui provient cette faculté d'intéroception, alors que l’insula et le cortex cingulaire antérieur ne fonctionnent plus ? Les neurologues ont supposé qu'elle dépendait des récepteurs cutanés de la poitrine situés au niveau du coeur, et du cortex somatosensoriel, qui traite les informations captées par la peau. En effet, des études d'IRM fonctionnelle avaient déjà montré que cette aire cérébrale s'activait lors de l'interoception, bien qu'elle eût semblé jouer un rôle secondaire.

Afin de vérifier cette hypothèse, Sahib Khalsa et ses collègues ont reproduit l'expérience en appliquant au préalable une crème anesthésiante sur la poitrine des sujets, à l'endroit où les sensations cardiaques avaient été les plus intenses. Or, cette fois, Roger n'a perçu aucune variation de son rythme cardiaque, bien que celui-ci se soit en réalité accéléré. En revanche, les sujets sains ont décrit des battements du coeur de plus en plus rapides, comme lors de la première expérience.

« L'insula est une aire importante pour la conscience corporelle, car elle participe à l'intégration des informations sensorielles, explique Christophe Lopez, de l'école polytechnique fédérale de Lausanne. Cependant, le cas de Roger montre qu'elle n'est pas absolument indispensable pour détecter notre rythme cardiaque, contrairement à ce que l'on pensait jusqu'alors. Il existe en effet une autre voie, parallèle et indépendante : la voie somatosensorielle qui provient des récepteurs de la peau ». Reste à savoir quelle est la fonction spécifique des deux circuits dans la perception de nos sensations internes.

Jacques Abadie

http://www.larecherche.fr/content/actualite-Sapiens/article?id=27180