Posts Tagged ‘prevention’

Trends in Intussusception Hospitalizations Among US Infants Before and After Implementation of the Rotavirus Vaccination Program, 2000–2009

27 May, 2012

See on Scoop.it – Virology News

“A small increase in intussusception rates was seen among infants aged 8–11 weeks, to whom most first doses of rotavirus vaccine were given, but no sustained population-level change in overall intussusception hospitalizations rates in US infants was observed after implementation of the US rotavirus vaccination program. Although an association between intussusception and rotavirus vaccination cannot be established by this ecologic analysis alone, even if the low risk with the first dose exists, it is outweighed by the well-documented benefits of vaccination of US infants”

This is a big deal- a very important, big deal: human rotavirus kills more than 500 000 people a year (mainly very little), and rotavirus vaccines have been bedevilled with the suspicion that they cause telescoping of the intestine, or intussusception.  Which can be fatal, and is not something you want happening to your healthy baby.

However, and however: I have taught my students for years to be aware of relative risks when talking about vaccines, and there is absolutely no doubt that even the Wyeth vaccine could have been considered “safe” in a developing country environment, where the threat of death due to diarrhoea and dehyderation caused by rotavirus, would have been far greater than any threat from the vaccine.

I thank Rusdsell Kightley Media for the rotavirus graphic

See on jid.oxfordjournals.org

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Muslim leaders enlisted to help stamp out polio

25 May, 2012

See on Scoop.it – Virology News

GENEVA (Reuters) – The last three countries where polio is still paralyzing children — Afghanistan, Pakistan and Nigeria — said on Thursday that they have enlisted Muslim women and religious leaders to allay fears of vaccination and wipe out the disease.
Polio cases are at an all-time low worldwide, following its eradication in India last year, raising hopes but also fears about a threat of resurgence especially in sub-Saharan Africa unless remaining reservoirs of polio virus are stamped out.

Conflict and insecurity is preventing health workers from reaching hundreds of thousands of children in Afghanistan and Pakistan with doses of polio vaccine, health ministers said.

See on www.reuters.com

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Radical Therapy for HIV-Infected People?

18 May, 2012

To mark HIV Vaccine Awareness Day, 18th May – Journal Club – Lucian Duvenage:

Excision of HIV-1 Proviral DNA by Recombinant Cell Permeable Tre-Recombinase

Mariyanna, L., Priyadarshini, P., Hofmann-Sieber, H., Krepstakies, M., Walz, N., Grundhoff, A., Buchholz, F., Hildt, E., Hauber, J., 2012. Excision of HIV-1 proviral DNA by recombinant cell permeable tre-recombinase. PloS One 7, e31576.

Introduction

HIV Life Cycle. Russell Kightley Media, http://www.rkm.com.au

Highly active antiretroviral therapy (HAART) is a combination of drugs that has significantly elongated the lifespan HIV-infected people. HAART targets viral reverse transcriptase, protease and integrase. There are disadvantages including drug toxicity and the appearance of drug resistant HIV strains in people not adhering to or withdrawing from their treatment. There is a need for new therapies that not only block virus replication but also eliminate HIV from persistent viral reservoirs. An attractive option is Tre-recombinase, which been shown to excise provirus from the genomic DNA of infected cell cultures. The development of Tre recombinase is a previous publication (Sarkar, I., Hauber, I., Hauber, J., Buchholz, F., 2007. HIV-1 proviral DNA excision using an evolved recombinase. Science 316, 1912-5.)

The Tre recombinase was created from the Cre recombinase which is a well-known tool in mouse genetics. The authors were able to alter the specificity of the enzyme by many cycles of directed protein evolution.

The Cre recombinase precursor removes genomic DNA that is flanked by two loxP sites by recombination. The authors were able to alter the specificity for loxP sites to HIV-1 LTR (long terminal repeat) sites. LoxP and the HIV LTR had 50% sequence similarity.

The main problem with the development of antiviral agents is the delivery to infected cells in vivo, without causing adverse side effects.  There are many reported technologies for the delivery of macromolecules such as proteins, nucleic acids or peptides. The most popular currently is the use of protein transduction domains (PTD) also known as cell penetrating peptides (CPP) from different sources. These have been useful for the delivery of various genes and proteins, including site-specific recombinases. The best studied and most applied PTD’s are peptides derived from the basic domain of HIV-1 Tat. But recently a powerful cell permeable translocation motif (TLM) has been described. This TLM is derived from a hepatitis B virus surface antigen. This TLM peptide is able to enter cells very efficiently, without affecting the integrity of the cells, or interfering with intracellular signal transduction cascades.

This paper describes the delivery of Tre-recombinase into cells using these PTD’s including HIV Tat and the HBV TLM. These so-called cell-permeable Tre-recombinases could eventually be useful for antiretroviral therapy, especially for virus eradication.

Results

Proteins

Different protein fusions were created and expressed in E. coli ; Tre-recombinase is fused to His tag, with/without nuclear localisation signal (NLS) and with the PTD (HIV Tat) or TLM (translocation motif derived from hepatitis B) or TLM as an inverted repeat.

They tested the cellular toxicity of the protein at their highest concentration by alarmBlue assay in HeLa cells. The proteins were incubated with the cells for 48 h. None of the proteins had any significant effect on the cellular metabolism

Cell permeability

Interestingly, all of the proteins entered cells, even those without a PTD or nuclear translocation signal. The authors explain that the Cre enzyme precursor to Tre has been shown to transduce into mammalian cells without any help, and therefore it is likely that the Tre enzyme shares this property. The authors did remark that the signal intensities were higher for those proteins with a PTD, indicating higher transduction efficiency.

Analysis of Tre activity in HeLa cells

A transient reporter assay demonstrated the activity of the Tre fusions: The reporter construct contains the target LTR sites that flank a puromycin resistance gene. Tre enzyme activity results in the loss of this gene, and gives a smaller PCR product using primers that anneal to the vector backbone. Cells transfected with the reporter construct were incubated with the 1 µM of the various proteins for 5 hours. The positive control was co-transfected with a construct expressing the Tre enzyme. PCR was performed on DNA extracted from cells after 48 hours. The presence of the smaller PCR product indicated that recombination had happened, as in the positive control. All of the proteins had varying degrees of activity, but notably the protein with the TLM PTD had the highest activity, with no un-recombined product detected by the PCR.

The authors went on to demonstrate that the Tre fusion proteins were active on at the genomic level, i.e. on chromosomal DNA. They used cells with the reporter construct was stably integrated into the genome.

Interaction of proteins with LTR sequences in living T-cells

Co-immunoprecipitation (ChIP) assays were done on using HIV-1 -infected T-cells (CEM-SS) to demonstrate the interaction of two of the Tre fusion proteins with the HIV LTR target sequences. The results showed that the proteins interacted with target LTR sequences in the genome of infected T-cells.

Microarray

The authors performed a transcriptome anaylsis on cells exposed to the Tre fusion proteins, using human whole genome microarrays. They concluded that the proteins were unlikely to have a significant effect on gene expression in the host cells, as very few genes were regulated more than 2.5-fold.

Recombination of the full-length HIV proviral genome:

Up to this point, the Tre fusion proteins had been shown to be capable of excising reporter construct gene flanked by LTR sequences both at the episomal level and the chromosomal level. The authors also showed that the proteins bind to the target sequences in HIV-infected living T cells.

It was essential that the Tre fusions could excise that HIV proviral genome from the chromosomal DNA of HIV-infected cells. The aouthors generated HeLa cells and T cells infected with pseudotype HIV-1. These are cells with the full-length HIV provirus integrated into the genome.They chose one of their proteins (TLM fusion showing highest activity in the reporter assays) for transduction into these cells. After transduction, PCR was performed to detect the HIV circular recombination product. They found that the recombination activity increased in a dose-dependent manner in both the HeLA cells and the T-cells. They also sequenced the PC products and were able to confirm HIV sequences.

Discussion

Some novel therapies for the treatment of HIV focus on the eradication of the virus in infected individuals. These include RNA-based technologies such as RNA aptamers, siRNA and ribozymes, but while these have shown to reduce viral load and viral replication, they have so far failed in virus eradication. A recent approach aimed at virus eradication is the reduction of surface CCR-5 receptors, through the expression of engineered zinc finger nucleases. This results in fewer CCR-5 surface receptors and could prevent new infection by CCR-5 tropic HIV.

The other approach is the use of site specific recombinases like Tre, which can excise the provirus from the host genome, thus potentially eradicating the virus from the individual. Ideally, the gene expressing Tre could be delivered to and expressed in target cells using a viral vector. But there are safety concerns as most of these are derived from pathogenic viruses. Therefore it may be advantageous to deliver the Tre enzyme directly to host cells. One way of doing this is through protein translocation domains (PTD’s). Protein transduction domains (PTD’s) can deliver bioactive molecules, including genes, siRNA, proteins or liposomes into all types of cells in vitro and furthermore into various organs in vivo. But they have not been applied yet for human use. PTD’s are easily fused to any target protein through cloning and expression of the fusion protein. The LTM used in this paper, derived from hepatitis B virus surface antigen, has low immunogenicity and high spreading capacity.

One strategy of using cell-permeable Tre enyme could be to harvest T-cells from the patient by apheresis and transduce them in vitro. They could then potentially be expanded and reinfused into the patient. This could complement or even replace gene transfer procedures.

In this paper the expressed Tre fusion proteins could enter cells and act on the target sequences to excise the HIV provirus from the genome, but the Tat fusion and the TLM fusion had higher activity than those that didn’t have a PTD tag. In particular, fusion to the newly described domain (TLM) from hepatitis B was resulted highest activity. This may explained by the fact that, in contrast to HIV Tat, TLM does not rely on endocytosis to enter cells. This might preserve enzyme activity and protein half-life.

In conclusion, cell permeable Tre enzyme could eventually be useful as an anti-HIV therapy in the post-HAART era.

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And while they were arguing about killer H5N1…

8 February, 2012

…Elsevier’s Virology was calmly publishing another paper on a “mutant” H5N1….

The abstract:

Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans. [my emphasis – Ed]

I have covered the use of glycan arrays to characterise influenza viruses’ binding specificity previously; I thought then, and do now, that it is a very cool technology – and one that has shown in this case that H5N1 variants can be selected from an originally “wild” population, that preferentially bind the human-type receptor.

And they did it like this:

To examine the functional evolution of H5 HA receptor specificity in the laboratory, we implemented an in vitro receptor-binding virus enrichment approach that recapitulates in vivo selection. Synthetic 6′-sialyl (N-acetyl-lactosamine) (6′ SLN) was used as the affinity ligand mimicking the human receptor to capture spontaneous viral receptor variants on the surface of magnetic beads. Starting with a pool of 108 EID50 of A/Vietnam/1203/2004 (VN04 virus), we performed four consecutive rounds of in vitro binding and elution followed by isolation of 150 individual virus clones by plaque purification and characterization by sequence analysis.

No “genetic engineering” here – or furore over “killer viruses escaping the lab!”  Possibly because (a) “mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets”, and (b) “a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets” [my emphasis].

Meaning they didn’t actually make anything that could immediately elicit such scare-mongering as the more notorious studies I and many others have reported on previously.

However, the grim NSABB folk were quick to decry the publication, saying “”I think it is fair to say that we would have liked to have seen it before it was published,” [Paul Keim, chairman of the National Science Advisory Board for Biosecurity], and the “…altered bird flu virus could mutate in dangerous ways if unleashed in nature”.

I am more worried, to be perfectly honest, over the dangerous ways the the wild type virus could mutate IN nature, given that mutants can be selected so apparently easily!

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Killer Flu hype grinds on

16 January, 2012

The Independent today has a story entitled”Killer flu doctors: US censorship is a danger to science” – thanks, AJ Cann! – which details how the folk in the Netherlands who did the work do not think the USA should not be “…be allowed to dominate the debate over who controls sensitive scientific information that could be misused in biowarfare terrorism”.

Influenza A viruses mixing in susceptible hosts

 

Well, yes, join the club, guys!  The article is quite reasonable – apart from a couple of points, noted below – but it ends on a suitably alarmist note “…the chances of a laboratory strain of H5N1 escaping into the wild remain high if it is stored in conventional flu-virus labs”, and “Regulators should not be sitting idly by, while the threat of a man-made pandemic looms”.  Really?  The undoubtedly very small amount of mutated flu that exists, relative to any engineered bioweapon in US or Russian labs, represents a clear and present threat to world health?

What dismayed me most, however, was how horrifyingly uninformed most of the commenters are – about H5N1 in particular, and science and science funding in general….!  As I could not comment there – Disqus broke, apparently – I will do so here.

As for labelling the article “Killer Flu Doctors” – really!  A little sensationalism, anyone??  Concerning the comment “…the details could be misused by rogue states or by biowarfare terrorists with access to rudimentary scientific knowledge and fairly standard laboratory equipment”: as a practicing molecular virologist, I can tell you that you would need a lot more than “rudimentary scientific knowledge” – you’d need skill in molecular biology, and especially in reverse genetics of (-)strand RNA viruses, as well as more than “fairly standard equipment” to even BEGIN to hope to make anything like a “killer” H5N1 from published details.

Additionally, a H5 N1 flu virus that is  aerosol transmitted in ferrets – and how efficient was that, I ask? – may NOT be similarly transmissible or as easily (if it was easy) between humans.  I will point out that people thought the SARS CoV outbreak was the “Big One” flu pandemic – but although it was aerosol transmissible, it wasn’t nearly as efficiently transmitted as the common flu, so did not spread as fast.

Thus, most of what the doomsayers are predicting could be simply hype – meanwhile, in countries far away from the US which seeks to regulate such work, the virus is already endemic, and mutating freely – and it would be VERY useful indeed to know what to look for!

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InCROIable Deux

1 March, 2011

In which the redoubtable Dorian reports further on the doings at CROI 2011.

Neutralizing HIV

Michel Nussenzweig (Rockefeller, USA) gave everyone an immunology lesson in order to explain what makes broadly neutralizing anti-HIV antibodies so special. So carrying on with the immunology lesson theme, I should just point out that neutralizing antibodies are those that not only stick to the surface of a virus, but actually prevent it from infecting a susceptible cell. So far, all effective antiviral vaccines work because they can induce these neutralizing antibodies. So that’s what neutralization is, now where does the “broadly” part come in? HIV is of course a highly variable virus, so “narrowly” neutralizing antibodies only neutralize a small number of HIV variants, while “broadly” neutralizing antibodies can block infection from a wide range of different HIV variants.

To date, none of the HIV vaccine candidates tested has been able to induce broadly neutralizing anti-HIV antibodies effectively, and most HIV-infected people do not make this type of antibody during natural infection. However some people with HIV infection do produce broadly neutralizing antibodies (It should be stressed however, that HIV+ individuals who make broadly neutralizing antibodies are not cured of their infection). The reason for studying antibodies from such people is that if we can understand how broadly neutralizing antibodies are formed during natural infection, then perhaps we might find a way to induce the same kind of antibodies with a HIV vaccine.

Using a variety of fantastically ingenious techniques, Nussenzweig showed us that the magical processes of hypermutation and affinity maturation are essential for the potency and the breadth of broadly neutralizing anti-HIV antibodies. These processes occur in the germinal centres of lymph nodes, and he presented some amazing imagery data to show that the maturation of antibodies is controlled by the CD4+ T-cells in the germinal centre that “help” B-cells produce antibodies. So the final message, I guess, is that CD4+ T-cell responses are going to be essential for a vaccine to be able to induce a good neutralizing antibody response.

However, that still doesn’t resolve the “broad” part of the problem – how to focus the antibody response onto the sensitive parts of the virus. Indeed, as a presentation in the afternoon from Laurent Verkoczy (Duke Univ. USA) showed, this may be extremely difficult to achieve. For one broadly neutralizing epitope on HIV (the so-called MPER epitope), the antibodies that bind to this site on the virus are also auto-reactive. In a mouse model, he showed that the cells that carry these antibodies are “strangled at birth” by the mechanisms that prevent our immune system from damaging ourselves. These antibodies have therefore probably been deleted from most people’s immune repertoire, and are therefore not available to be selected and amplified by vaccination.

So I’m afraid no-one has yet found the way to induce these broadly neutralizing antibodies.

A virus that slows down HIV

GBV-C is a virus infecting humans that is transmitted by sex, blood transfusion, and from mother to child – rather like HIV. It is a flavivirus (other family members include yellow fever virus, and hepatitis C virus), and because of its mode of transmission, GBV-C is often found in HIV seropositive people. It does not seem to cause disease in people who are infected either acutely, or chronically. Now, you might expect that being infected by two different viruses at the same time would be worse than just being infected by one. But remarkably, the 20-40% of HIV+ individuals who have chronic GBV-C infection have SLOWER disease progression than those who only have HIV infection (at least in European/North American patient cohorts).

There were two talks presenting results trying to explain this intriguing observation. Molly Perkins (NIAID, USA) presented data from a study of HIV-infected patients in the Gambia. She found that GBV-C coinfection did not change T-cell activation, but reduced expression of the HIV coreceptor CCR5 on T-cells. In direct contrast to these results, Jack Stapleton (U Iowa, USA) presented data showing the exact opposite. In his study, GBV-C lowered T-cell activation, but had no effect on CCR5 expression.

How can two groups looking at the same question get such discordant results? Jack Stapleton noted that the different studies on this topic have been conducted in different regions of the world. Both HIV and GBV-C show geographical variation – that is to say, the HIV that infects people in Iowa is not the same as the HIV that infects people in the Gambia, and the same goes for GBV-C. So one plausible explanation may be that different types of GBV-C have different biological effects.

Not wanting to send the room into an uproar, I didn’t ask the question that immediately sprung to my mind – when are we going to test GBV-C infection as a therapeutic intervention?

Dorian
Lecturer in Microbiology, University of Nantes

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InCROIable…Dorian McIlroy reports

28 February, 2011

The penalty for winning a competition here on ViroBlogy is writing an article for ViroBlogy – 2nd prize would, of course be writing TWO articles.  Mind you, as two-time winner, regular commenter Dorian McIlroy gets to do just that.  He has volunteered to report daily from CROI 2011, the 18th Conference on Retroviruses and Opportunistic Infections in Boston, that’s on right now.  Thanks Dr D!

“So here I am in the snow in Boston at the 18th CROI. The opening talk is from Bryan Cullen (Duke, USA) on viruses and micro RNA, known as miRNA. As readers may know, there are three main functions types of RNA inside cells. Messenger RNA (mRNA) is the intermediate between a sequence of DNA and the protein that the DNA sequence encodes. It carries the message, so to speak, telling the protein synthesis machinery what protein to make.  The two other main types of RNA (tRNA and rRNA) are involved in the translation of the mRNA message into protein.

However, in addition to these common or garden types of RNA, cells also produce very small RNA molecules, that do not code for proteins, and are not directly involved in protein synthesis. So what are they for? Well, we will have to wait till Prof. Cullen tells us. Right now, John Coffin (Tufts, USA) is giving the opening talk. There are about 4000 delegates, all lined up in a big auditorium. As you can imagine, the speaker is a little tiny blob at a lectern way, way up at the front. Fortunately, the
speaker’s head and torso is projected on a big screen at the same time.  The films of all the talks are available on the CROI website (www.retroconference.org), which kind of defeats the purpose of  my writing these blog posts I guess…..[NO!  Ed]

But  on with Bryan Cullen. miRNAs are expressed in all multicellular organisms. There are over 1000 of these miRNAs in humans, and their role is to regulate mRNAs – so in fact they control gene expression. In plants and insects, some miRNAs have anti-viral functions, but this is not the case in mammals. In fact, at least one human virus (HCV) uses a host cell miRNA for its own replication.

In addition, some DNA viruses – mostly herpesviruses – also code for miRNAs. One of these is Epstein-Barr Virus (EBV) which is associated with several cancers. When EBV infects B-lymphocytes from the blood, these cells grow in an uncontrolled way (that is, they become pre-cancerous).   It turns out that only one of the EBV miRNAs (BHRF1-2 if you really want
to know) is involved in turning normal B-cells into pre-cancerous cells.  Dr Cullen then goes on to explain an interesting technique called “PAR-CLIP” that allows you to identify the target genes of a particular miRNA, and gives us a list of the cellular genes targeted by  BHRF1-2.

Take-home message – some oncogenic DNA viruses use miRNAs to manipulate host cell biology, and this is involved in their ability to induce cancer.

This is followed by a harrowing story from Fred Hersch, of his own brush with death due to HIV/AIDS. Fortunately, he survived, due to the extraordinary efforts of the ICU at St Vincent’s hospital in New York, and is now playing piano for us all.

After the musical interlude, Anthony Harries (now at the International Union against TB and kung diseases in Paris) gives an excellent talk (hey – not that the first talk wasn’t excellent too) describing his time as head of HIV/AIDS health care in Malawi. He was there when HIV seroprevalence rose from less than 1% to about 15% in the adult population. For several years in the 1990s and the beginning of the century, no treatment was available to stop people from dying. During that
period, 90% of patients diagnosed with stage 4 AIDS were dead one year later. That began to change, he says, with the world AIDS conference in Durban in 2000, where international efforts to make antiretroviral therapy (ART) available in sub-Saharan Africa began to take shape. He then goes on to explain how ART is implemented in Malawi – and shows how coffin sales in one district have plummeted over the last few years. This is the real clinical success of making ART available – the decade-long wave of deaths has abated.

That was the good news. Now for the bad news. Transmission rates are still high – with an estimated 70 000 new HIV infections in Malawi each year. So the HIV problem has certainly not gone away, it has just been contained.  Secondly, current guidelines for starting ART depend on a HIV+ individual’s CD4+ T-cell count, and if you don’t have the means to determine the CD4 count (of the 400 ART centres in Malawi, only about 50 have the machines to measure CD4 T-cell counts), then you can’t start treating all the people who need it. He ends by making a convincing case for, at the very least, giving ART to all pregnant seropositive women in Malawi (and I guess, in the whole of Africa), with a clear recommendation that they continue on medication indefinitely. The objectives of this approach would be to keep mothers alive and healthy while their children
are growing up, and to ensure that the next generation of children are born HIV-free.

And that’s it for the first day.”

Dorian

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Prophylactically yours….

7 December, 2010

It’s not often we have something to report on locally – I rely on Alan Cann to do that…B-) – but I am very pleased to be able to do so now.

Hot on the heels of another South African success in the fight against HIV and AIDS comes the news (from the UCT Monday Paper) that:

Prophylactic antiretrovirals could check HIV infection

Assoc Prof Linda-Gail BekkerBeing there: UCT’s Assoc Prof Linda-Gail Bekker led the South African component of the six-country study on the prophylactic use of an antiretroviral tablet.

It’s a long way from being the final word in HIV prevention, but a major study involving UCT researchers and published in the New England Journal of Medicine reveals that the daily use of an antiretroviral tablet as a prophylactic could curb infection among those at high risk by nearly 44%.

The findings are based on an HIV-prevention trial conducted at 11 international sites in six countries (including the Desmond Tutu HIV Foundation [DTHF], associated with UCT’s Faculty of Health Sciences), from June 2007 to May 2010. The study, named the Pre-Exposure Prophylaxis Initiative (iPrEx), looked at the prophylactic use – in other words, for people not infected with HIV – of a tablet that contains two widely-used HIV medications, emtricitabine and tenofovir (FTC/TDF).

Results showed that high-risk individuals – men and transgender women who have sex with men – who took the tablet experienced an average of 43.8% fewer HIV infections than those who received a placebo. In all, 64 HIV infections were recorded among the 1 248 study participants who received a placebo pill, while 36 HIV infections were recorded among the 1 251 participants who received the study drug.

The iPrEx study found that this pre-exposure prophylaxis (PrEP) was more effective among those who reported taking the pill more regularly. Among participants who used the tablet on 50% or more of days, as measured by pill counts, bottle counts and self-reports, risk of HIV infection fell by 50.2%; while among those who used the pill on 90% or more of days, as determined by the same measures, the PrEP pill reduced infection risk by 72.8%.

“I think this is a very significant study in that what we have here is the first proof of concept that taking an antiretroviral prophylactically – in other words, taking it before exposure to HIV – would actually prevent HIV infection,” says UCT’s Associate Professor Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Centre.

tablets (brand-named Truvada)As the tablets (brand-named Truvada) are readily available, anyone can buy and use these. But Bekker is quick to point out that a lot of work still has to be done on the treatment, especially on its use outside of trial conditions. (For example, the tablet can affect renal and liver function, so participants’ kidneys and livers were monitored closely.)

Also, those recently infected and still developing antibodies to the HIV (ie seroconverting) are cautioned not to take the tablet, as it exposes the virus to two agents, upping the risk of building resistance to the treatment. “You may inadvertently affect or impact your chances of good treatment down the line,” says Bekker.

Naturally, high-incidence countries like South Africa will take plenty of interest in the study. But at around R400 for 30 tablets, this may not be the treatment to turn things around for the country.

“It is unlikely that we will be able to treat our way out of this epidemic,” said the DTHF in a statement. “We are going to have to find innovative, affordable and practical ways to stop the ongoing transmission of HIV.”

Fortunately, the study found that participants did not relax their use of safer-sex practices. On the contrary, self-reported HIV-risk behaviour decreased among participants, while condom use increased.

Professor Anna-Lise Williamson, of UCT’s Institute for Infectious Disease and Molecular Medicine and a member of the South African AIDS Vaccine Initiative, welcomes the treatment as another valuable advance in curbing the spread of the disease, but remains cautious of the human-behaviour element. For one, she says, people have to recognise that they are at risk before they’ll commit to the tablet.

“But it gives people options, and the more options they have, perhaps they’ll find a prevention strategy that suits their lifestyles,” she says. “But in the long term, I still believe we need a vaccine to prevent HIV infection.”

Concerns about risk compensation – increases in risky behaviour prompted by decreases in perceived risk – will remain, says Bekker. For this, education will be essential.

Also, the tablet’s use as a prophylactic will have to be but one tool in an arsenal of measures.

“We’re going to have to layer different kinds of preventative strategies together to come up with foolproof prevention,” Bekker warns, “but it’s probably not going to be dependent on only one strategy.”

Amen.  So we have – in order of increasing efficacy – an HIV candidate vaccine regime, a vaginal gel, and now pre-exposure prophylaxis.  And if you combine them…??  Basically, an additive effect – except that the vaccine is not available….  Time to fast-track, people!!

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