I am never opposed to more press coverage of HIV, but the big story today seems to be an old one. The CDC reports that instead of the approximately 40,000 new HIV infections in the U.S every year, in 2006 we actually had about 56,000 new infections. That’s a huge difference. They used a new surveillance method to come up with this number.


As you may note (as carried in this blog), the same data were released on World AIDS Day last year. The Wall Street Journal reported then that the U.S. incidence was about 60,000.  The CDC is saying this is a wake-up call—but the wake-up call should have been (at least) 8 months ago! Well, we’ve never done enough on HIV, and I don’t think the increased U.S. incidence estimates will do anything to change that. Should we start taking bets on whether HIV gets any debate time in the upcoming elections?


M. Linde


Let me start by saying that I’m a product of the Hildreth lab, so I am fairly well-versed in the trojan exosome hypothesis. Basically, the hypothesis, as presented by Drs. Hildreth and Gould, is that HIV particles are basically glorified exosomes. They postulate that the HIV budding machinery usurps the normal exosome budding machinery to produce virions. Accordingly, HIV virions are pretty similar to exosomes, except that they carry the viral payload. There are a number of lines of evidence that suggest this, most of them outlined in the PNAS hypothesis paper published about 5 years ago.


Now, there are a number of people who don’t believe this is the case—some of them pretty prominent. I’m not writing to either support or refute the exosome hypothesis, but rather to discuss a paper that came out of David Ott’s lab claiming to refute the trojan exosome hypothesis.


A number of groups have noticed that CD45 is missing in viral particles. This observation is part of the evidence for HIV budding from lipid rafts—although I don’t really believe lipid rafts exist; I am much more partial to tetraspanin enriched membranes. In any event, one way to get highly purified viral particles is to run supernatant from infected cells through a series of density gradients, take the pellet, and then deplete for CD45. This gets rid of contaminating vesicles that contain CD45, leaving purified viral particles. A number of groups claim that exosomes also do not contain CD45, which would mean that CD45 depletion would leave both exosomes and HIV particles. Lori Coren reports in Retrovirology that depleting supernatant from Jurkat and SupT1 cells of CD45 removes exosomes, suggesting that HIV particles and exosomes differ in CD45 composition and, therefore, likely do not share the same budding process.


They really state their case with one figure, although it’s split into six parts. They isolated exosomes from the two cell lines, depleted half for CD45 and then blotted for CD45, actin and did silver stains for total protein. After depleting they observed no CD45, no actin, and I think no protein (I think they mislabeled part of the figure). They did the same thing for infected cell lines, except that they also blotted for p24. They found pretty much the same thing, although actin shows up in the Jurkat/HIV supernatant that was CD45 depleted and you can see protein (mostly viral proteins) in the CD45 depleted samples. They claim that CD45 depletion leaves virus (we know that), but not exosomes. They claim that the reason other groups didn’t find CD45 in exosomes was because they were using anti-CD45 antibodies that don’t recognize the cytoplasmic domain of the protein, while they use a pan-CD45 antibody that will recognize more isoforms. I’m not sure how immunoprecipitating with antibodies that recognize the cytoplasmic domain of a protein will pull out intact vesicles, but with this paper, it’s beside the point.


Now, their findings may be true, but this paper has several flaws preventing me from accepting their conclusions. Anyone who has tried to isolate exosomes knows that it is a total pain in the ass. They are hard to define biochemically, which is why in almost every paper you see on exosomes, exosome presence is confirmed by electron microscopy. Based on this paper, we have no idea what this group is actually working with. You can’t show the depletion of exosomes if you don’t show that the exosomes are there in the first place. And there is no control for depletion using markers we know are on exosomes (like CD81) and markers that we know are excluded. I would be much more inclined to believe the results if they showed depletion using some unrelated antibody, like an anti-GFP, didn’t produce the same effect. How do we know that their immunoprecipitation itself didn’t affect the outcome? There’s no protein left after immunoprecipitation and it’s not like Jurkats and SupT1s pump out exosomes; they may just not have enough protein in their sample following depletion to detect by Western blot. And why don’t you blot for exosome markers while you are at it? If you are going to do biochemical analyses, at least do it thoroughly.


So, I think if they added some controls, this could be an interesting observation. As it is, it doesn’t clarify anything.


M. Linde

A recent PNAS paper with a huge group of authors from UAB and about half a dozen other universities (Shaw and Hahn are in the grandfather spots), attempts to discern whether there are conserved features of the HIV envelope (Env) gene at the time of transmission. I believe that this type of study is probably our best shot at developing a preventative vaccine.


I’ll explain. There is always interplay between viral diversity (quasispecies) and the host immune response. With less immune pressure, virus can replicate readily and the most fit viral quasispecies will dominate—that is, there is no selective pressure to drive viral evolution and, therefore, less viral diversity in the host. With heavy immune pressure, there is selection for whichever viral quasispecies can evade this pressure—again leading to less viral diversity in the host. Somewhere in the middle you get a scenario where the immune system exerts enough pressure to drive viral diversity, yet not enough pressure to control replication. So, you get a high number of quasispecies. Why is this important? Well, quasispecies and viral diversity are some of the problems for developing a vaccine; it’s difficult to effectively target many slightly different viral sequences. However, when HIV is transmitted, it may go through a “bottleneck”; there may be constraints on which viruses are fit to establish infection, so only a few viral quasispecies may be involved in the establishment of infection. So, if we can figure out the envelope sequences for these viral variants that are transmitted, we could potentially develop a vaccine to target these sequences.


The problem is that it’s not terribly easy to find these sequences. By the time most people reach treatment, the virus has long since passed this bottleneck and they have a large number of viral variants. Finding those patients who have been recently infected is difficult. On top of that, there are technical issues in figuring out the envelope sequences of the viral variants which established infection. Lastly, it’s entirely possible that a person may be infected with several different viral variants during transmission.


This may be the reason why there are about 30 authors on this paper—this is hard stuff. Keene and colleagues had access to samples from 102 acutely infected patients. They had stored blood on which they could sequence the patient’s envelope gene. Each patient had their HIV Env genes sequences an average of 25 times. As there are multiple sequences (HIV often mutates quite rapidly, as you may have heard), the authors used mathematical modeling to try and determine which sequence likely established infection (the founder sequence). Now, I am certainly no mathematician (one of the reasons why my lab work was less than stellar), so I can’t comment on the model they used. As usual, the validity of this sort of study depends in large part on the validity of the model, so just remember that these findings may be colored by their choice of model.


The authors found that 78 of the subjects had Env gene sequences that suggest infection with a single virus (homogeneous infection). The other 24 subjects showed evidence of infection with multiple quasispecies: around 2-5 different variants (heterogeneous infection). This is important because, in conjunction with similar studies, it appears that infection frequently occurs from establishment of a single or a few viruses. If these viruses have common features, then we can design a vaccine to target these features.


The authors then tested 55 of these envelope proteins for some common features. They found that 54 of these Env proteins were CCR5 dependent—something we’ve known for a while, but it always good to see further validated. The other envelope protein was dual-tropic. All of the envelopes were susceptible to several broadly neutralizing monoclonal antibodies (mAbs), while most were resistant mAbs targeting the V3 loop of the viral envelope. It appears that the V3 loops of these proteins are hidden from the antibodies, and not absent. They also found that the viral Env gene does not appear to mutate very rapidly in the period up to peak viremia, which you might expect if the patient does not mount a robust immune response to the virus (see above). The authors comment that “studies aimed at further analyzing Env glycoproteins of transmitted or early founder viruses may help to identify unique features and potential vulnerabilities relevant to vaccine design. Beyond this, the present study illustrates a strategy for identifying and characterizing full-length genomes and proteomes of transmitted or early founder viruses including, but not limited to, HIV-1. Such analyses may facilitate a better understanding of virus natural history and virus-specific cellular and humoral immune responses in naive and vaccinated individuals.”


The authors also note that different modes of transmission may lead to different founder Env sequences. So, it may be that there may eventually (hopefully?) be a vaccine that has sequences designed to target sexually transmitted HIV and sequences designed to block HIV transmitted through needle-use. The authors are currently looking at whether there are differences in the Env genes based on mode of transmission.


For those of you that follow this stuff, there are some other interesting observations in this paper, including 13 subjects who had G-to-A hypermutation in the HIV genome, indicative of APOBEC deamination, and the longitudinal evolution of Env followed in 10 subjects.


Of note, this study followed acute infection with clade B virus, which is likely necessary for studies conducted among US and European patients. Clades C and E virus dominate in Africa and Southeast Asia, so these sorts of studies need to be conducted among those populations to help elucidate the differences in transmitted virus among the different clades. I believe that some of this work is also being conducted, so it will be interesting to see if there are any conserved features of the virus during transmission and if these features are observed across clades. I hope so, because that would be the ideal scenario for vaccines designed based on these findings.


M. Linde

Apparently, the FDA is investigating Bristol-Myers Squibb and GlaxoSmithKline for the drugs didanosine and abacavir, respectively. Data from The DAD Study Group published in the Lancet suggests that these drugs are associated with a higher risk of myocardial infarction. One can only assume that the FDA is under increased scrutiny for these types of events considering the recent history of Vioxx. 

While the findings of the DAD group were unexpected, I think an FDA investigation is utterly ridiculous. As I am sure you are well aware, HIV is a fatal disease when untreated. These drugs are truly life saving. I am not saying they don’t have some serious side effects, but increasing an already very low rate of MI among high risk patients should not be a primary barrier to prescribing these drugs. Conducting this investigation will only serve to scare patients away from these antiretrovirals (and maybe other antiretrovirals), which would not be a good thing. 

Now, having said that, I can’t help but find myself wondering whether the abacavir hypersensitivity reactions, slight increase in MIs, and recent troubles in ACTG 5202 (among which was an increase in general adverse events) have something in common. Could there be some inflammatory effect with abacavir? I don’t know and I probably shouldn’t even write this, as there’s no data to back it up. It would be interesting if there was a common etiology, though.

M. Linde

There was a brief report in Nature Biotechnology that recently caught my eye.  The title wasn’t a big draw (“HIV Vaccine Controversy”), but I have to admit I was intrigued that it was in Nature Biotechnology. I thought it had the potential to discuss some real basic immunology. Of course, it turned out to be a news story and didn’t have any real science in it.

I’m glad I came across the article, though, because it’s an interesting story. Essentially, the International AIDS Vaccine Initiative (IAVI) conducted a vaccine trial among 30 participants in India despite the fact that the vaccine had been shown poor results in an earlier European trial. The IAVI claims that it did not act unethically, which I agree with. They argue that response to the vaccine could differ by host genotype, which presumably would be different between your average European and your average Indian. However, I found myself wondering why the IAVI didn’t try and enroll different ethnicities in the European trial—certainly they could have found 30 Indians living in Europe. I don’t know the details, but maybe the IAVI had a good reason for structuring this trial the way they did. 

Still, the whole thing sounded bad, so I am sure the IAVI will be a little more careful in the future. 

M. Linde

A new story came out from Fauci’s lab at NIAID indicating that the HIV spike component gp120 can bind the integrin alpha4 beta7 (a4b7). The gp120 protein is responsible for HIV binding to CD4; it is also known that it can bind some other molecules, most notably galactoceramide. The physiologic ramifications of gp120 binding to proteins other than CD4 is not really known, although I think most feel that it is not a major contributor to HIV disease. 

The a4b7 story seems to have a little more importance, though. Integrins have been known to be important for HIV attachment, as they are found on the virus and studies have shown that if you block the integrin interactions (particularly the ICAM-1/LFA-1 interaction), you decrease HIV attachment. Fauci’s group, led by James Arthos, found the interaction while investigating CD4 T cell depletion in the gut associated lymphoid tissue (GALT). Early in HIV infection, CD4 cells undergo a massive depletion in the gut—the site of approximately 2/3 of CD4 cells in the body. It’s believed that this massive insult is important to establishing chronic infection and disease. One of the hypotheses for the massive infection and depletion in the gut is due to the high number of CD4+ CCR5+ T cells in the gut. However, the mechanisms for this depletion are not yet worked out—hence the new paper in Nature Immunology from this group. 

They started with natural killer (NK) cells, which do not express CD4 (although I believe NK T cells do), yet have disrupted activity by gp120. The researchers found that gp120 binds the NK cells, but only in the presence of calcium. Using binding studies with cell lysate and mass spectrometry, the authors found that HIV binds the integrin a4b7. Furthermore, they found that this binding activates the integrin (as measured by phosphorylation of p38 mitogen-activated kinase). These findings also hold for T cells. The authors note that T cells in the periphery have low levels of active a4b7, but that T cells in the gut have high levels of the activated integrin. This integrin is actually important in signaling T cells to migrate to and stay in the gut. Therefore, the authors used PBMCs (not from the gut), stimulating them with retinoic acid to achieve a “gut-like” phenotype. Now, it is difficult to differentiate whether the gp120 is binding to CD4 or to a4b7, so the authors conducted their binding studies in the presence of a monoclonal antibody that blocks the CD4-gp120 interaction. They noted gp120 binding to T cells in the presence of the antibody. This binding was not evident in the absence of calcium, suggesting that the binding was mediated by a molecule other than CD4. The binding was also abrogated when they added the a4b7-ligand MadCAM (sounds like the name of a heavy metal band, right?). The authors also blocked the interaction using three other antibodies that interact with a4b7. They observed similar results for CD8 cells. So, the binding studies seem pretty solid to me. 

The next order of business was to find the a4b7-gp120 binding sites. Since gp120 binding activates the integrin, it makes sense that gp120 might bind the same region as the natural ligands. A hexapeptide mimicking the MadCAM binding site inhibited gp120-a4b7 binding in a dose-dependent manner. The gp120 molecule has a region similar to the MadCAM binding site. One amino acid in this region is conserved in more than 98% of the gp120 sequences in the Los Alamos database; it’s in the V2 loop of gp120. Using site-directed mutagenesis and binding studies with surface plasmon resonance, the authors confirm that the binding site is in the HIV V2 loop. These gp120 mutants could still bind CD4, but had little CD4 independent binding. 

Apparently, not all gp120 molecules bind a4b7 with the same efficiency. The “V” in the “V2” loop stands for “variable”, which would explain differences in binding ability between gp120 molecules. Previous studies with the chimeric SHIV (a mix of HIV and SIV) produced two viral variants with differential ability to infect the GALT. One strain is CXCR4 oriented and the other is CCR5 oriented (see an earlier post for an explanation of this if you need it). As noted above CCR5+ CD4+ T cells are more highly expressed in the GALT than in the periphery. The authors tested the ability of gp120 from these viruses to attach to T cells with the gut phenotype. They found that in the presence of CD4-blocking antibody, the gp120 from virus that preferentially infects GALT has residual binding, while the other variant does not. They also discovered that the difference in biding is due to the differences in the V2 loop binding site, suggesting that the background binding in the absence of CD4 is a4b7 mediated and that the variant which infects GALT better has better CD4-independent binding. 

Finally, the authors wondered whether this binding has any functional significance. LFA-1 activation is linked to the a4 molecule. LFA-1 also happens to be a really important player in the immune response, forming part of the immunologic synapse (the pSMAC—peripheral supramolecular activation complex). Everyone knows that HIV needs activated T cells to replicate. As you might expect, gp120 that has the ability to bind a4b7 and this activates LFA-1, facilitating the clustering of LFA-1 and CD4. So, this could help the virus enter the cell. Of course, these sorts of things are also dependent on the stoichiometry of an interaction, so there is no telling whether this occurs under physiologic conditions. Bombarding a cell with recombinant gp120 is vastly different than having variable viral levels. So, you have to make that caveat. 

However, the group conducted some in vitro studies showing that the gp120-a4b7 binding is important for HIV replication. PBMCs cultured in retinoic acid had decreased viral replication when exposed to viral variants with mutated V2-loop binding sites; although this is not necessarily due to decreased a4b7 binding (it’s only suggestive). 

The authors make three arguments that this interaction is important:

·        “The highest frequencies of HIV-1 infection occur in the memory CD4+ T cell compartment in the gut, in which, unlike in almost all other tissue compartments, memory CD4+ T cells express activated a4b7.”

·        “Second, this interaction is well conserved. We have shown that gp120 proteins derived from HIV-1 subtypes A, B, C and D, as well a simian immunodeficiency virus (SIVsmm) gp120, bound to a4b7.”

·        “Finally, we have shown that gp120 activated LFA-1 in an a4b7-dependent way. The capacity of LFA-1 to increase the efficiency of HIV-1 infection is well established.” 

Is this an important observation? Well, it’s certainly an important basic science observation; the physiological relevance remains to be determined. If a4b7 is important in the establishment of infection, then this might offer a way to either prevent initial infection or lessen the impact of initial HIV pathogenesis in the GALT. At best, this could potentially prolong HIV disease progression. That’s still a long way off, though, so it will be interesting to see where this goes. It appears that there are a4b7-blocking agents in development, so studies in animal models may help clarify some of these questions. 

I would also like to point put that there are 21 authors on this paper. For those of you that haven’t worked in laboratory science, it often (but not always) takes this many people to produce a high-quality paper. It’s one of the reasons why PhD studies now take closer to 6 or 7 years, and not the traditional 4 years, and that post-doctoral fellowships have been extended by 2-3 years. It makes me think that the traditional endpoint of PhD candidacy should have less emphasis on publication, because—speaking from experience—it is very difficult to compete with large groups working on similar projects. But that’s another story.

M. Linde

I read in the Wall Street Journal today that Pfizer is going to try and reformulate maraviroc (Selzentry) as a microbicide—something I have been saying they should do ever since I saw the efficacy data. Maraviroc is exciting because it is a new class of drug. It’s an entry inhibitor that works by blocking HIV’s interaction with one of the co-receptors, called CCR5. 

For those of you who don’t know, HIV predominantly uses two different co-receptors. The CD4 molecule is the primary receptor. HIV binds CD4, which causes a change in the viral entry proteins, allowing them to bind the co-receptor and enter the cell. Along with CCR5, CXCR4 acts as a major co-receptor (there are other minor co-receptors that HIV can use, but I am not sure how important these players are). So, any cells that HIV is going to infect need to have CD4 and either CXCR4 or CCR5. These are mainly CD4 cells, which carry CXCR4 and sometimes CCR5, and macrophages, which have CD4 and CCR5. 

A virus can be CCR5-trophic, CXCR4-trophic, or dual trophic. These used to be called M-trophic and T-trophic (for macrophage and T-cell, respectively), but these names changes when the co-receptors were discovered. As you might have figured out, M-trophic virus is also CCR5-trophic and T-trophic is CXCR4-trophic. When someone is infected with HIV via sexual contact (I am not sure about intravenous transmission), the virus that is almost always transmitted is CCR5-trophic. (One day I need to write about the viral genetic shift to baseline during transmission).  For some reason, the predominant strains in the body shift to CXCR4 as disease progresses. I don’t know this for fact, but I had always assumed that the reason why the transmitted virus is CCR5-trophic is because of virus-macrophage interaction in the genital tract. This could be totally wrong, though, so please don’t take this as fact. 

Getting back to Maraviroc, you might understand how a CCR5-inhibitor might have some limitations. First, it would only be effective for patients that have predominantly CCR5-trophic virus. This means you have to test the patients for their predominant strain, which can be expensive. Second, viral trophism changes and patients at later stages of disease progression tend to have the CXCR4 virus. Therefore, maraviroc would probably be useful for patients at earlier stages of disease progression, like first- or maybe second-line. The problem is that we already have good regimens for first line therapy, so maraviroc would have to be pretty efficacious to crack the line-up. The other problem is that most medications start as salvage therapy (multiple failures); maraviroc is probably not going to help these patients because it likely won’t be active against their viral strains. So you can see where Pfizer might have a problem with this drug. It is approved for human use, though, so why not try to use it in another manner? 

It seems to me like a good candidate for a microbicide. It’s a small molecule, so it should be fairly stable. Formulation is always an issue, but the real test is going to be what it does to the genital tract. We know it has antiviral activity—that’s not the issue. But there are a lot of compounds that have antiviral activity, which doesn’t mean they’ll work as microbicides. One of the more famous cases is nonoxinol-9, the spermicide. It can kill virus and was thought to be a potential microbicide. The problem was that it increased the infection rate, instead of decreasing it (sound familiar?). It turns out that N-9 also causes inflammation, and HIV loves inflammation. So, any compound that works as a microbicide cannot be inflammatory. Another issue is that microbicide trials are essentially like vaccine trials; that is, they are big and expensive. Last year a promising microbicide was halted early during Phase III trials because it increased the transmission rate. This trial had over 3,000 patients and was at something like eight trial centers on three or four continents. Lastly, it may be that a microbicide is going to need to be used in combination with another microbicide, similar to HAART. This would be to prevent the development of strains that are resistant to the microbicide. Unfortunately, we don’t have any microbicides right now, so that would be a problem. 

I hate to end on a pessimistic note, though. I think it is great that Pfizer is taking my advice and doing this (well, they never consulted me, but they should have). Not only do I hope it is successful, I hope maraviroc makes oodles of money as a microbicide and spurs other pharmaceutical companies to look at microbicide development as a viable business plan. 

M. Linde

The FDA approved Tibotec’s Etravirine (TMC 125) on Friday—the first new non-nucleoside reverse transcriptase inhibitor approved in almost 10 years. Just thought you might be interested. Apparently, it will cost about $8,000 a year.

M. Linde

I’ve just spent the last hour comparing what’s found in HIV virions with what host factors the virus needs to produce virions. Chertova et al. published a great paper a few years ago in the Journal of Virology where they used mass spectrometry to determine what proteins are found in HIV particles produced in macrophages (primary cells). Brass and colleagues recently published a study in Science in which they used an RNAi knockdown screen to determine what host proteins are needed for viral production in HeLa and TZM-Bl cells (cell lines). It is very important to note that HeLas and TZM-Bls (which I believe are derived from HeLas, if memory serves) are very different cells from primary macrophages, so you might expect that HIV might have different requirements for each cell type and that some of the proteins found in one cell type may not even be present in the other types. Just to give you an idea of how different they are, macrophages are monocytic cells that are isolated from donors and can remain in culture for maybe a month (longer maybe?) and HeLa cells are epithelial cells originally derived from a cervical cancer tumor in 1951 at Hopkins. They’ve been around for over 50 years and they grow like weeds. That’s my caveat.

What I noticed between the two studies is that there is virtually no overlap in the proteins found. Now, some of this is because of the assays used—the Brass study failed to find some of the proteins that we know are needed for HIV production, so we know that the screen didn’t identify all the proteins involved in HIV production. Also, Brass ruled out any knockdowns that severely limited cell viability or growth; some of those proteins might be found in the virus. I won’t rule out the human factor either, since the Brass article uses protein abbreviations and the Chertova article uses full names (my eyes are only so good, folks). Still, the amazing lack of concordance is really striking. Of all the proteins found in each of the studies (~200 each), I could only find one host protein that is both necessary for viral production and is also found in the viral particle: KIFC3 kinesin. I don’t know anything about this protein specifically, except that it is a motor and probably is involved in viral protein trafficking. It’s also interesting that the mass spec paper identified a bunch of Rab and VPS proteins that are incorporated in the virions and the RNAi paper found members of these classes that are needed for production—just not the same proteins. This could be due to trafficking differences between the cell types, but I found it odd that none of the proteins from these classes overlapped in the two studies. 

I am still not sure what this means. I have always felt that the host proteins found in the virion are probably important or necessary for viral production. However, after studying this in the lab for four years and having little-to-no success, maybe I need to reevaluate this stance. Certainly, the lack of correlation between these studies can be due to a number of factors. Also, the fact that host proteins in the virion may not be necessary for viral production may not mean they are not important in HIV disease. I would really like to see someone use these two assays in one paper to try and make some of these correlations. Even better, I wish someone would do an RNAi screen and produce virus, testing whether virus produced is less infectious. This might be a great way to produce a therapeutic vaccine. 

M. Linde

Ok, so I am sure the title of this entry will be the standard joke among HIV docs for a bit. Actually, it has probably been made far too many times already. The joke is based on recent data indicating that Viread (FTC/TDF) was shown to decrease the rate of vaginal infection among humanized mice. The mice essentially have human immune systems, which is why the can acquire HIV. Mice that received pre-exposure prophylaxis (PrEP) with Viread did not get infected when exposed vaginally, while 88% of the mice that did not receive PrEP acquired infection. The mice that received PrEP were given Viread 48 hrs and 24 hrs prior to HIV exposure and every 24 hrs for 5 days after exposure. The study was published by Denton and colleagues in PLoS Medicine this month. 

So, these data are kind of exciting. It’s humanized mice, so you can’t get too excited yet. I would assume a monkey study would be next and then a large-scale human trial. You have to take animal studies as they are—they don’t always translate to the same results in humans. But the data could be a boon for high-risk populations, especially women. One of issues with condoms is that it requires the cooperation of your partner. If there is an alternate method to block infection—one that does not require the partner’s cooperation—hopefully the transmission rate might be reduced. This could also be really helpful for serodiscordant couples who want to conceive. Granted, sperm-washing techniques (the process of eliminating virions from semen) are very successful, but this might be considerably less expensive and a lot easier. Viread PrEP could also be helpful for intravenous drug users, but it has yet to be established (as far as I know) if this method would protect against HIV acquired via needles.

Of course, there are also concerns. While I don’t think anyone would advocate using Viread PrEP instead of condoms (especially at this point), we have to establish whether Viread PrEP is as efficient in preventing infection as condom use. If PrEP with Viread is not as efficient as condom use for blocking infection, then you have to question the common utility of Viread PrEP. Additionally, condom use is one time and Viread PrEP might require a weeks worth of adherence, which might be difficult for some. Finally, Viread is not without side effects, although I doubt this would be a major concern considering Viread’s toxicity profile and the fact that the dosing would be intermittent instead of chronic. And cost is always an issue, especially in underdeveloped nations where HIV transmission is rampant. 

All in all, the study is good news. We desperately need more ways to prevent infection. A pill is a good start as it would help circumvent some of the social and political problems faced with condoms. We still need a barrier microbicide, but the data for PReP are encouraging. So, assuming this does work, does Viread go over the counter?

M. Linde