The rather disappointing 39% reduction in HIV infection among women who received tenofovir microbicide gel during the clinical trials has since been written about as if it is going to turn the epidemic around. It might, but the reduction would need to be a lot higher than 39%. A lot of questions will also need to be answered about the way the CAPRISA 004 trial was run and reported on.
But immediate efforts have been made to 'fast-track' approval so that the gel can be produced commercially. A site has already been identified for the factory, which makes it sound as if the many further trials that are needed to establish if the gel is going to have any impact at all on the HIV pandemic are irrelevant.
Any drug that is overused carries the risk of widespread resistance. This is something pharmaceutical companies are acutely aware of, given the substantial increase in their profits when people need to change to a newer and inevitably more expensive drug as a result of resistance. But if millions, perhaps tens of millions, eventually use this gel, levels of resistance could go far beyond what could be controlled (whatever level that might be).
And an important question, apparently, is that the reasons behind the HIV transmissions during the trial, and therefore the effectiveness of the Tenofovir drug, are not yet clear. One researcher has suggested that anti-inflammatories may be useful in reducing HIV transmission.
Another question that has been raised about effectiveness is that it is possible the gel only protected women if the viral load in their partner's semen was high. The trial results made public were a bit vague about exactly what risks were faced by the women who became infected, and if all of them were really infected sexually. Perhaps the less flattering results of the trial will be made public now?
Showing posts with label microbicide. Show all posts
Showing posts with label microbicide. Show all posts
Monday, June 20, 2011
Wednesday, July 28, 2010
HIV Treatment As Prevention; the Hole in the Patch
Various factions in the HIV industry, and indeed some in the global health industry, are like a bunch of inept tinkers trying to patch up a colander in the hope that they can use it as a pot. They all rush to one hole and stick their latest ill-gotten patch on it, and then stand back to see how well it works. Invariably it doesn't work, but they churn out some more patches and stick them on other holes that they belatedly start to notice. Sooner or later there are patches on top of patches and, alas, still too many holes for boiling cabbage.
What the industry has always tended to miss is that when they try to stick on a patch, for example, by telling everyone about how HIV is transmitted and how they can avoid being infected, they find that there is no infrastructure for this to be effected. There are too few schools, too many students, too few teachers who know too little and too many barriers for some people to go to school or for others to gain much by doing so. A large proportion of the population does not have access to the mass media, which may or may not have the freedom to do what the HIV industry would like them to do.
Once testing was possible, this too was 'rolled out'. And over 20 years or so, about 20-25% of people in developing countries found out whether they were infected or not. It was established that HIV was transmitted sexually and that condoms gave good protection against infection. So condoms were distributed and people were encouraged to use them. Estimates of condom usage vary but it has been difficult to get condoms to the right place in time and to encourage consistent use. But health facilities, both primary health care facilities and others, such as pharmacies and sexually transmitted infection clinics were underfunded, understaffed and oversubscribed. To many, they were completely inaccessible.
So it was expected that educating people about HIV and providing them with what meager facilities were available would be a good place to start. But many people didn't go to school and schools were not very good. And many people didn't go to hospitals and they weren't very good either. The majority of HIV 'prevention' strategies were stymied not because they were rubbish (though many were), but because there were certain prerequisites that hadn't been met. Obvious though some of these prerequisites were, health, education, infrastructure, social services and the rest, they are still wanting.
HIV is not the only disease that has attracted this kind of 'vertical' approach, nor the only disease that the global health industry has failed to have much impact on. There is a whole set of water-borne diseases, some of which have been approached individually, some not. Most of these efforts have failed, not because the diseases can't be prevented and/or cured but because people who suffer from them are still drinking contaminated water. Clean water and adequate sanitation would enable people to avoid some of the most debilitating and deadly diseases.
Respiratory infections kill millions of people, especially infants and under fives. But the environmental and other conditions that result in these infections killing so many have not been dealt with. Many infants die because they don't receive even the most basic level of care; young children die of measles and meningitis; mothers die because of inadequate maternal care; and people of all ages die of malaria, TB and other treatable and curable diseases.
Ensuring health is not about curing diseases, it is about providing people with the conditions that will allow them to avoid these diseases. But the tinkers in the industry think they can run around after sick people and thereby keep others healthy. 'Treatment is prevention', the idea that putting all HIV positive people on antiretroviral drugs so that they are less likely to transmit the virus to others, will fail. It will not fail because the drugs don't work, they do. But most people have not been tested; others refuse to take the drugs; others don't have access to the drugs; and others still take the drugs but they don't work. And while this is going on, far too many people are still being infected with HIV.
Developing countries do not have the infrastructure to test every single sexually active person, let alone test them every year. They don't have the capacity to supply every HIV positive person with drugs, to monitor them, treat them and support them adequately. You can introduce 'task shifting' (a proposed alternative to providing enough trained professionals), microbicides that may work a little, circumcision that probably won't work very well and any other patches the tinkers can dream up. But those basic things that people need most correspond to their human rights.
Allowing people their human rights may not result in HIV being eradicated quickly, given that it has been spreading so long and has infected so many. But the only hope for reducing transmission to the extent that the virus can be eradicated completely is for all those infected to receive treatment and care and for all those who are HIV negative to be provided with everything they need to ensure their complete health. And providing treatment and care and preventing the further spread of HIV requires good health services, schools, infrastructure and public services. Overall health doesn't result from targeting a handful of diseases. Rather, overall health and well-being in a population means that most diseases can be targeted, treated and controlled.
What the industry has always tended to miss is that when they try to stick on a patch, for example, by telling everyone about how HIV is transmitted and how they can avoid being infected, they find that there is no infrastructure for this to be effected. There are too few schools, too many students, too few teachers who know too little and too many barriers for some people to go to school or for others to gain much by doing so. A large proportion of the population does not have access to the mass media, which may or may not have the freedom to do what the HIV industry would like them to do.
Once testing was possible, this too was 'rolled out'. And over 20 years or so, about 20-25% of people in developing countries found out whether they were infected or not. It was established that HIV was transmitted sexually and that condoms gave good protection against infection. So condoms were distributed and people were encouraged to use them. Estimates of condom usage vary but it has been difficult to get condoms to the right place in time and to encourage consistent use. But health facilities, both primary health care facilities and others, such as pharmacies and sexually transmitted infection clinics were underfunded, understaffed and oversubscribed. To many, they were completely inaccessible.
So it was expected that educating people about HIV and providing them with what meager facilities were available would be a good place to start. But many people didn't go to school and schools were not very good. And many people didn't go to hospitals and they weren't very good either. The majority of HIV 'prevention' strategies were stymied not because they were rubbish (though many were), but because there were certain prerequisites that hadn't been met. Obvious though some of these prerequisites were, health, education, infrastructure, social services and the rest, they are still wanting.
HIV is not the only disease that has attracted this kind of 'vertical' approach, nor the only disease that the global health industry has failed to have much impact on. There is a whole set of water-borne diseases, some of which have been approached individually, some not. Most of these efforts have failed, not because the diseases can't be prevented and/or cured but because people who suffer from them are still drinking contaminated water. Clean water and adequate sanitation would enable people to avoid some of the most debilitating and deadly diseases.
Respiratory infections kill millions of people, especially infants and under fives. But the environmental and other conditions that result in these infections killing so many have not been dealt with. Many infants die because they don't receive even the most basic level of care; young children die of measles and meningitis; mothers die because of inadequate maternal care; and people of all ages die of malaria, TB and other treatable and curable diseases.
Ensuring health is not about curing diseases, it is about providing people with the conditions that will allow them to avoid these diseases. But the tinkers in the industry think they can run around after sick people and thereby keep others healthy. 'Treatment is prevention', the idea that putting all HIV positive people on antiretroviral drugs so that they are less likely to transmit the virus to others, will fail. It will not fail because the drugs don't work, they do. But most people have not been tested; others refuse to take the drugs; others don't have access to the drugs; and others still take the drugs but they don't work. And while this is going on, far too many people are still being infected with HIV.
Developing countries do not have the infrastructure to test every single sexually active person, let alone test them every year. They don't have the capacity to supply every HIV positive person with drugs, to monitor them, treat them and support them adequately. You can introduce 'task shifting' (a proposed alternative to providing enough trained professionals), microbicides that may work a little, circumcision that probably won't work very well and any other patches the tinkers can dream up. But those basic things that people need most correspond to their human rights.
Allowing people their human rights may not result in HIV being eradicated quickly, given that it has been spreading so long and has infected so many. But the only hope for reducing transmission to the extent that the virus can be eradicated completely is for all those infected to receive treatment and care and for all those who are HIV negative to be provided with everything they need to ensure their complete health. And providing treatment and care and preventing the further spread of HIV requires good health services, schools, infrastructure and public services. Overall health doesn't result from targeting a handful of diseases. Rather, overall health and well-being in a population means that most diseases can be targeted, treated and controlled.
Sunday, July 25, 2010
Was the Tenofovir Gel Microbicide Trial Ethical?
Was the trial ethical and were the results valid? The two questions go hand in hand.
It's quite hard to decide if there was something unethical or invalidating about the Tenofovir Gel Microbicide trial because there could be important details about the trial that have not yet been published. For a start, the trial assumes that most HIV transmission among the participants is sexual. But did the researchers involved actually establish that HIV transmission was all or even mostly sexual? If they did, they haven’t said so in the paper.
The question is important because, during the course of the trial, researchers would have had the opportunity to find out, for each participant who became infected with HIV, how they became infected. One might say they had a duty to find out how they became infected. Were the partners of all the women who seroconverted HIV positive? I don't believe this data was collected. If it was, it should have been published because those who were infected non-sexually should have been excluded from the results. The gel is supposed to protect against heterosexually transmitted HIV, not, for example, HIV transmitted by unsafe medical procedures.
Participants were given the gel as a prophylactic against HIV. They were given to understand that they would be protected against HIV infection. They wouldn't have been told that they were protected against non-sexual HIV transmission. But they don't appear to have been warned about the possibility of non-sexual transmission. If the researchers didn’t exclude the possibility of non-sexual HIV transmission, and they don’t appear to have done so, the results are of questionable validity.
Nearly 900 people were recruited to take part in a trial and it was known that some, perhaps a lot of participants, would become infected with HIV before the end of the trial. It was not known how many would become infected or which participants. Perhaps non-participants in the area may face an even higher risk of becoming infected. But I don't think that excuses those running the trial for failing to ensure the safety of those taking part, or for failing to establish the cause of each HIV infection.
Participants were "provided with comprehensive HIV prevention services (HIV pre- and post-test counseling, HIV risk reduction counseling, condoms, and STI treatment), reproductive health services...". They were made aware of the risk of being infected with HIV sexually, but not non-sexually; this is not comprehensive. But despite this preparation, which surpasses the level of prevention available to most people in most African countries, HIV transmission rates were extremely high.
Why, given all these precautions, including very high condom use, were transmission rates so high? And why did the researchers not make any attempt to find out how people were becoming infected? Did they not have a duty to find out if their gel could even have had any influence on rates of HIV infection, or what level of influence it could have had?
In fact, it is not accurate to say that "All women were counselled on the risk of HIV and encouraged to use condoms at all times..." as one report said. All women were counselled on risks of *sexual* HIV transmission. Condoms wouldn't have been much use if any of the women were infected non-sexually.
A BBC article inadvertently puts its finger on the problem: "A vaginal gel has significantly cut the rate of women contracting HIV from infected partners...". But the trial has not established if partners were infected or uninfected. So we don't know if the vaginal gel has achieved this, or exactly what it has achieved.
The same article goes on: "Such a gel could be a defence for women whose partners refuse to wear condoms." But reported levels of condom use were very high and they increased during the course of the trial. Condoms should be far more effective than they appear to have been during this trial. Condom manufacturers must be asking if it is safe to use the gel when using condoms or if the gel actually weakens them or causes them to burst. I certainly hope they are asking these questions.
The article cites one of the researchers as claiming: "Women who used the gel more consistently were much less likely to be infected…". But women using the gel more consistently also had less sex. And those having more sex tended to use the gel less consistently. It's hard to know exactly how to interpret the results of this trial. If the results were truly valid and significant, how would we know? The research seems to be incomplete in many ways.
Executive director of UNAIDS, Michel Sidibe, is quoted as saying: "For the first time we have seen results for a woman-initiated and controlled HIV prevention option." Well here's another one: Patient Observed Sterile Treatment (POST). In order to protect themselves from non-sexual HIV transmission, people need to be made aware that HIV is not always transmitted sexually and of the precautions they can take. Concentrating on sexual risk alone leads to the sort of travesty that this gel trial appears to have been. If the Executive director of UNAIDS is not aware of this, he should resign.
Can we say clearly that the results of the trial could not have been due to chance? Technically, the result is statistically significant, other things being equal. But we just don't know enough (or are not being told enough). The paper notes that, "Overall, condoms were reportedly used in 80.3% of sex acts; increasing from 78.5% in the first 6 months to 84.3% in months 18-24". This means that as condom use went up, the efficacy of the gel seemed to go down.
The paper goes on "we observed declining HIV incidence rates in the placebo gel arm. This may have been due to their declining coital frequency and increasing condom use." So, are they saying that over time, the efficacy of the placebo gel increased as the efficacy of the Tenofovir gel decreased? That seems like a strange result. If the trial had gone on for five years, would these two trends have continued? Not only is the trial questionable ethically, it is also of questionable validity.
The trial could be unethical because the researchers would have known in advance, or should have known in advance, that at least some HIV is transmitted non-sexually. Yet they made no effort to protect people from this. Nor did they make any effort to inform people that such a risk exists. And the results are of questionable validity because we don't know how people became infected and, therefore, why some people didn't become infected. There could have been many factors that increased the risk of infection and others that decreased the risk. Tenofovir gel may have had some effect, but we don't know what effect it had or why it had an effect.
It's quite hard to decide if there was something unethical or invalidating about the Tenofovir Gel Microbicide trial because there could be important details about the trial that have not yet been published. For a start, the trial assumes that most HIV transmission among the participants is sexual. But did the researchers involved actually establish that HIV transmission was all or even mostly sexual? If they did, they haven’t said so in the paper.
The question is important because, during the course of the trial, researchers would have had the opportunity to find out, for each participant who became infected with HIV, how they became infected. One might say they had a duty to find out how they became infected. Were the partners of all the women who seroconverted HIV positive? I don't believe this data was collected. If it was, it should have been published because those who were infected non-sexually should have been excluded from the results. The gel is supposed to protect against heterosexually transmitted HIV, not, for example, HIV transmitted by unsafe medical procedures.
Participants were given the gel as a prophylactic against HIV. They were given to understand that they would be protected against HIV infection. They wouldn't have been told that they were protected against non-sexual HIV transmission. But they don't appear to have been warned about the possibility of non-sexual transmission. If the researchers didn’t exclude the possibility of non-sexual HIV transmission, and they don’t appear to have done so, the results are of questionable validity.
Nearly 900 people were recruited to take part in a trial and it was known that some, perhaps a lot of participants, would become infected with HIV before the end of the trial. It was not known how many would become infected or which participants. Perhaps non-participants in the area may face an even higher risk of becoming infected. But I don't think that excuses those running the trial for failing to ensure the safety of those taking part, or for failing to establish the cause of each HIV infection.
Participants were "provided with comprehensive HIV prevention services (HIV pre- and post-test counseling, HIV risk reduction counseling, condoms, and STI treatment), reproductive health services...". They were made aware of the risk of being infected with HIV sexually, but not non-sexually; this is not comprehensive. But despite this preparation, which surpasses the level of prevention available to most people in most African countries, HIV transmission rates were extremely high.
Why, given all these precautions, including very high condom use, were transmission rates so high? And why did the researchers not make any attempt to find out how people were becoming infected? Did they not have a duty to find out if their gel could even have had any influence on rates of HIV infection, or what level of influence it could have had?
In fact, it is not accurate to say that "All women were counselled on the risk of HIV and encouraged to use condoms at all times..." as one report said. All women were counselled on risks of *sexual* HIV transmission. Condoms wouldn't have been much use if any of the women were infected non-sexually.
A BBC article inadvertently puts its finger on the problem: "A vaginal gel has significantly cut the rate of women contracting HIV from infected partners...". But the trial has not established if partners were infected or uninfected. So we don't know if the vaginal gel has achieved this, or exactly what it has achieved.
The same article goes on: "Such a gel could be a defence for women whose partners refuse to wear condoms." But reported levels of condom use were very high and they increased during the course of the trial. Condoms should be far more effective than they appear to have been during this trial. Condom manufacturers must be asking if it is safe to use the gel when using condoms or if the gel actually weakens them or causes them to burst. I certainly hope they are asking these questions.
The article cites one of the researchers as claiming: "Women who used the gel more consistently were much less likely to be infected…". But women using the gel more consistently also had less sex. And those having more sex tended to use the gel less consistently. It's hard to know exactly how to interpret the results of this trial. If the results were truly valid and significant, how would we know? The research seems to be incomplete in many ways.
Executive director of UNAIDS, Michel Sidibe, is quoted as saying: "For the first time we have seen results for a woman-initiated and controlled HIV prevention option." Well here's another one: Patient Observed Sterile Treatment (POST). In order to protect themselves from non-sexual HIV transmission, people need to be made aware that HIV is not always transmitted sexually and of the precautions they can take. Concentrating on sexual risk alone leads to the sort of travesty that this gel trial appears to have been. If the Executive director of UNAIDS is not aware of this, he should resign.
Can we say clearly that the results of the trial could not have been due to chance? Technically, the result is statistically significant, other things being equal. But we just don't know enough (or are not being told enough). The paper notes that, "Overall, condoms were reportedly used in 80.3% of sex acts; increasing from 78.5% in the first 6 months to 84.3% in months 18-24". This means that as condom use went up, the efficacy of the gel seemed to go down.
The paper goes on "we observed declining HIV incidence rates in the placebo gel arm. This may have been due to their declining coital frequency and increasing condom use." So, are they saying that over time, the efficacy of the placebo gel increased as the efficacy of the Tenofovir gel decreased? That seems like a strange result. If the trial had gone on for five years, would these two trends have continued? Not only is the trial questionable ethically, it is also of questionable validity.
The trial could be unethical because the researchers would have known in advance, or should have known in advance, that at least some HIV is transmitted non-sexually. Yet they made no effort to protect people from this. Nor did they make any effort to inform people that such a risk exists. And the results are of questionable validity because we don't know how people became infected and, therefore, why some people didn't become infected. There could have been many factors that increased the risk of infection and others that decreased the risk. Tenofovir gel may have had some effect, but we don't know what effect it had or why it had an effect.
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