Universal Access to Water Before Universal Access to PrEP

With the buzz that tends to be drummed up when a clinical trial is not, at least on the surface, a complete failure, it is easy to forget what things are like in countries with high HIV prevalence. IRIN has an article about health systems in Kenya needing an overhaul and the frequency of drug shortages and stock outs. Uganda, Tanzania and other countries have similar problems.

This is not just about drugs. On my other blog yesterday, I cited a systematic review of healthcare associated infections which noted "inadequate environmental hygienic conditions; poor infrastructure; insufficient equipment; understaffing; overcrowding; paucity of knowledge and application of basic infection-control measures; prolonged and inappropriate use of invasive devices and antibiotics; scarcity of local and national guidelines and policies [and] reuse of scarce resources, such as needles and gloves."

This is not just about HIV, either. People suffer from and die from preventable and curable diseases, conditions that are cheap and easy to prevent and cure. Many of these diseases relate to a complete lack of basic scientific, health and hygiene knowledge. Many relate to lack of basic rights, such as clean water and sanitation and a healthy environment.

Many people in East African countries have little or no access to health facilities and it's difficult to know how to view that problem. Because many are infected with various 'hospital acquired infections' (HAI) in health facilities, such as HIV, hepatitis, bacterial infections, urinary infections and numerous others. In fact, high rates of HIV are often correlated with relatively high access to health facilities. The lowest rates are often in places where people don't have access to health services.

Large scale rollout of antiretroviral drugs (ARV) has had mixed results, with many people continuing to die of preventable and treatable conditions, such as TB. The number of people on ARVs is quite a small proportion of those who need them. And countries with big programs are depending on donor funding, which is not guaranteed to get any higher, and may even drop.

So the questions are: will health systems be improved enough to make a better job of supplying the enormous number of people who would be in need of PrEP than has been done with ARVs? Where will all the money come from and will the problem of ARV rollout be solved at the same time? Will health issues other than HIV receive the attention they deserve or will people with needs that can be resolved cheaply and simply continue to be ignored?

PrEP is just a pill, it is not the means for ensuring that people who need it receive it and take it as prescribed for as long as they need it. That's no different from ARV treatment, either. But with ARVs, we know that a sustained program with a wide enough reach is still pretty elusive.

So why are we talking about PrEP as if it is anything more than a theory? Universal access to clean water and other basic rights should have been provided before ARVs, at least people would have something with which to swallow the pills. Otherwise, we're just tinkering with the problem.

Experts More Muted About iPrEx Results Than Media

The iPrEx trial tested truvada as an oral pre-exposure prophylaxis for men who have sex with men (MSM). The results were moderate, showing a 44% efficacy. The result would have been far higher had adherence been higher. But if adherence was something that could be assured, high and consistent rates of condom use would make PrEP irrelevant.

From what I can work out also, the study did not test the partners of those who became infected with HIV during the trial. This makes the claim that those taking the drug were protected from sexual transmission, as opposed to some kind of non-sexual transmission, somewhat tenuous. This question is crucial and is still hanging over the equally hyped CAPRISA 004 trial, which tested the use of 1% tenofovir as a vaginal gel.

As a result of very low adherence to the drugs in the iPrEx trial, it is not possible to claim with any confidence that resistance will not develop where those taking the drug become infected with HIV, but where the infection is not detected in time. Most of those who seroconverted were not following adherence advice. HIV strains resistant to truvada were detected in two participants who entered the trial with HIV infection that was not detected until later.

The issue of how early HIV infection is detected in people taking PrEP is very important. How regular would testing need to be for the threat of resistance to be minimized? Most people never get tested. Some test once in their life. Very few test regularly. Would quarterly, or even yearly testing ever be logistically feasible or affordable?

Resistance is not just a danger for the person taking PrEP; resistant strains of HIV can be transmitted, perhaps even to people taking the same PrEP formulation. Worse still, resistant strains could infect large numbers in certain sexual networks, for example, where MSM are targeted as an especially high risk group.

Whatever about the use of this drug in rich countries, the feasibility of using it in developing countries seems pretty low. Levels of side effects were not high, but that's not so comforting given that adherence was so low. The drug itself is very expensive but the cost of regular testing of millions of people, even the very possibility of such an undertaking, makes it a luxury that few could afford. Dropping the price of the drug will not make the cost of large scale rollout of PrEP any more affordable.

Interestingly, it is reported in the appendix that rates of receptive intercourse dropped sharply in the first 12 weeks and stayed at about half what they were at the start. Use of condoms during receptive intercourse increased to a high level, also during the first 12 weeks, and stayed high for the rest of the trial. Similar patterns of protective behavior were noted in the CAPRISA 004 trial.

These findings suggest that even people thought to be at high risk of contracting HIV are amenable to taking precautions. Sadly, rollout of PrEP is not expected to include rollout of similar levels of support and monitoring found in clinical trials. But most sexually active people in some African countries seem to be at high risk of HIV infection and health facilities are unable to contain the endemic chest and diarrheal conditions that kill so many, let alone HIV.

Dr Joseph Sonnabend has a good critique of iPrEx which is worth reading in its entirety. It seems as if those who want to latch on to anything that can be dressed up as good news are being allowed free rein to do so. But those who treat the issue more thoughtfully, and that includes those involved in the trial, don't seem to be shouting from the rooftops.

Treatment as Prevention: Treating People to Death

There was an attack on 'treatment as prevention' in March which came from a person you wouldn't expect to oppose a technological quick fix, Elizabeth Pisani. Despite the fact that she disagrees with UNAIDS in some ways, she is an adherent of the behavioral paradigm. It seems a pity to hold views that challenge the mainstream and yet still cling to the mainstream's central premise about HIV: that it is almost always transmitted through heterosexual sex in African countries.

But it's worth citing her opposition to a strategy which has a lot in common with PrEP. Firstly, Pisani points out that "HIV is most infectious in the few months after a person is first infected. Even if everyone got tested annually, we’d miss most of these new infections." I hope the 'modelling' work that is said to support treatment as prevention includes this point, but I doubt it.

Pisani also notes that there are a number of circumstances under which viral load (infectiousness) can spike, such as contracting another sexually transmitted infection (or perhaps other diseases) or failure to take medication correctly, which can occur for many reasons. Such a spike would increase infectiousness in people who may well be engaging in unprotected sex.

Pisani refers to findings relating to treatment becoming more widely available in rich countries. Apparently rates of unprotected sex increases as a result of 'disinhibition', engaging in unprotected sex in the belief that the risk is now low. Many have claimed that disinhibition does not happen to any great extent in African countries. The 'model' used by proponents of treatment as prevention believe that disinhibition will not significantly contribute to HIV transmission and that adherence to drug regimes will be extremely high in African countries.

Pisani casts doubt on both of these claims. I have to say, I agree. I would suggest that the finding that disinhibition is low in African countries is more likely to indicate that HIV is not as closely related to sexual behavior as we have been led to believe.

As for claims about high levels of adherence, I'm not sure if figures for treatment in countries like Kenya and Tanzania are very complete or credible. Death rates among HIV positive people seem to be high enough to keep prevalence steady and there is no evidence that sexual behavior has been influenced greatly by behavior change programs.

I'd say UNAIDS, and Pisani herself, are over-optimistic about a lot of things. Treatment as prevention sounds, on the surface, like a good idea. But it's not going to be enough on its own, especially if only sexually transmitted HIV is being targeted. Waiting till people become infected and then treating them, hoping that they will all become less infectious and therefore slowing down the epidemic, is ludicrous.

Even if HIV is 100% sexually transmitted this would not work. We must know by now how hard it is to influence people's sexual behavior or, indeed, any other kind of behavior. But HIV is also transmitted non-sexually. It is vital to establish the contribution of non-sexual HIV transmission to serious HIV epidemics, otherwise sexual transmission will continue to be overestimated. As long as we overestimate sexual transmission, HIV will continue to spread.

HIV Still Holds Good Opportunities for Investors

A worrying aspect of the ever increasing medicalization of health, including HIV/AIDS and other diseases that are especially common in developing countries, is the question of how the commodities involved will be paid for. Many people advocating the greater use of drugs, perhaps most, have an interest of some kind, financial, political, career related, perhaps all of these.

But the fact is, people in developing countries can not pay for expensive commodities. And there's no reason why they should do so when their most urgent needs are not commodities, they are basic human rights, such as food, water and sanitation, basic health services, education, infrastructure and other social services. People don't generally die for want of expensive medication, though they often die for want of very cheap medication, medication which is too cheap for Big Pharma to be interested in.

Protesters in India have been arrested for arguing that the European Union (EU) is threatening the production and use of cheap generic drugs by hoodwinking India into signing a 'Free' Trade Agreement (FTA), which will 'allow' India to export some of its products in greater quantities to Europe, but at derisory prices. In reality, the agreement is so that European countries can export their overpriced goods, often goods that are only likely to benefit wealthier Indians, to a country that has no need of these goods.

Medicins Sans Frontieres is running a campaign to prevent the EU from abusing its power in this way (email the EU trade commissioner to protest!). The FTA would apply to all drugs, whether intended for primary health or otherwise, whether lifesaving or not. It would also apply to all other goods and the conditions go beyond what is required by the World Trade Organization's Trade Related Aspects of Intellectual Property Rights agreement (TRIPS). Those who naively support the greater use of PrEP could take a little time to consider if such a strategy would really benefit people who are most at risk of HIV infection.

Drop Everything, A Vaginal Gel Has Been Developed

Chi Mgbako writes an article entitled "International donors must fund female-controlled HIV prevention gel", but this raises a number of issues.


Is a vaginal gel, as Mgbako and others argue, female controlled? One would think that if it is, so are oral contraceptives. Yet, the majority of women in many developing countries opt for injectible contraceptives. They say their husbands object to them taking contraceptives, so they get an injection every three months, possibly running the risk of picking up some blood-borne infection at the clinic, perhaps even HIV. Will the same husbands that object to oral contraceptives ignore vaginal gels? Has this even been tested?

Also, this article mentions a number of things that are in need of change, such as domestic violence and gender inequality. These are in need of change regardless of HIV transmission. Is the author advocating that these and other social problems be ignored as long as vaginal gel is paid for by international donors and some (rather small) percentage of HIV infections are possible prevented?

I don't think the author is making the argument that these other social problems are insignificant or that HIV reduction should be chosen over other social problems. Rather, it needs to be made clear that that is something international donors do.

Numerous social problems have been alluded to as causing HIV transmission, allowing HIV transmission, assisting HIV transmission, etc. But most of these problems are independent of HIV, they existed before HIV and they won't just go away on their own.

But HIV programs have a tendency to ignore contexts to the extent that HIV testing clinics are set up in areas where people are dying of contaminated water related diseases, respiratory infections, intestinal parasites and other treatable and preventable conditions. HIV programs are, no matter how much those in the HIV industry would like to argue otherwise, deflecting attention from real and preventable problems.

And to what end? That we might be able to reduce HIV transmission by 39% (in ideal, trial related scenarios)?

Finally, if the gel is so good, why have funders not come up with the funding? Is there something they know that we are not allowed to know? Other HIV related drugs have made billions, why are international funders drawing back from this one?