Research tries to explain why HIV transmission is sexist

Dr. Jonathan M. Carlsons main goal Is to develop statistical models able to help understand the HIVs adaptive response to the immune system. He has been working closely to biological and medical researchers

Men and women that have sex with men have greater chances  (2 and 20 times more, respectively) to be infected by the HIV than heterosexual men. To analyze the theme, a study  published on Science Magazine revealed that the viruss genetics has an important role in this. The work developed by researchers from Microsoft Research and Emory University details how only the agent´s strongest strains tend to infect heterosexual men. For this, they used data from a long research about HIV transmission between heterosexual dissenting couples (one is HIV positive and, the other, negative) in Zambia. Below, one of the works coordinator, Dr. Jonathan Carlson  talks about the theme to the Brazilian Society of Tropical Medicine (BSTM).

BSTM: What was the main goal of the research?

J.M.C: HIV is characterized by a rapid rate of mutation that results in a high level of viral genetic diversity within each infected individual. Nevertheless, new infections are typically established by a single genetic variant that comes from the cloud of viruses circulating in the donor. Our question was whether there was anything special about that “founder” virus, or if founder viruses are simply those that happened to be in the right place at the right time.

BSTM: Which were the main results achieved?

J.M.C: Our data show that, while there is a significant amount of chance involved, luck favors the viruses that have a higher level of “fitness.” That is, viruses that are predicted to reproduce at faster rates. Fitness was estimated by a number of features, but the most striking feature was that viruses whose RNA sequences were closest to the sequence we most commonly see in Zambia were those that were most likely to be transmitted. This suggests that these common sequences (“consensus”) are common because they have a transmission advantage. Additionally, we found that this transmission advantage was stronger for men than for women. This means that there is a higher fitness barrier in men, leading to stronger selection pressure. Thus, men are less likely to be infected than women, but when they are infected, it is typically be fitter viruses that result in more severe disease. In a similar manner, men with genital ulcers or inflammation were more likely to be infected, and thus infections were more frequently established by less-fit viruses.

BSTM: Despite dealing only with heterosexual couples, how could you conclude that homosexual relations are more susceptible to HIV transmission?

J.M.C: It is difficult to speculate beyond the data available in this study. But we expect that the general paradigm will hold: higher infection risk means a lower genetic barrier. This means when infection does occur, it will typically be established by lower-fitness viruses that will lead to less severe disease.

BSTM: How can this work help us better understand the transmission of HIV among humans?

J.M.C: It shows that exposure frequently results in the non-productive infection of target cells, providing a window in which stronger viruses can outcompete weaker viruses, as well as a window in which vaccines or drugs may be able to raise the bar for any virus to be able to establish systemic infection. It also shows that any approach that leads to less fit viruses (such as drugs or immune responses that select for certain escape mutations) will lower overall transmission rates. It also suggests that preventative vaccines or drug therapies have a window of opportunity in which to work, but that a side effect of the increased barrier to entry will be that breakthrough infections that do occur will typically be established by highly fit viruses that may lead to more severe disease.

BSTM: Do the researchs results show that hardly a vaccine would be able to protect against all HIV versions?

J.M.C: It suggests that vaccines should focus on regions of the virus that are highly conserved—that is, where there is very little genetic variation circulating in the population. In our data, viruses that had mutations in these highly conserved regions were least likely to be transmitted, so if we can focus the immune response on these regions, we will block the most common circulating variants and ensure that circulating mutant viruses that are naturally resistant to the vaccine will be less likely to transmit due to their resistance mutations. This approach is already in development by several groups; our data provides important justification for these approaches and further insights into how such vaccines may work.

BSTM: Is there any perspective of more promising results regarding AIDS combat for the next few years? Please, explain.

J.M.C: The most important recent result in controlling transmission is the observation that providing drugs to either infected individuals or high risk, uninfected individuals will greatly reduce transmissions. Our work sheds some light on how these approaches work and makes some predictions on possible side effects. Most critical is the importance of follow-up studies to ensure that breakthrough infections among individuals taking preventative drugs do not result in a more clinically severe disease. Our results suggest that such breakthrough viruses will be characterized by higher fitness, but clinical research will be required to determine whether this results in important differences in clinical outcomes.…