Wednesday, July 6, 2011

Blurring the line between Prevention and Treatment

Test and Treat:  Blurring the line between Prevention and Treatment

By Sean McShee

Test and Treat forms part of the family of new tools for HIV prevention, labeled “Treatment as Prevention”.  In this family of tools, the lines between prevention and treatment blur; the same anti-retroviral treatment that made HIV a semi-manageable disease becomes a tool for HIV prevention.  While the other tools in this family require HIV negatives to utilize some aspect of anti-retroviral treatment, with Test and Treat, the direct treatment of HIV positives indirectly minimizes the risks of transmission to the uninfected.  Two potential dangers exist with Test and Treat:  the over-treatment of HIV positives in treatment and the confusion of individual level viral load with community level viral load.  As Test and Treat both improves the health of the infected and prevents transmission, it is the most cost effective HIV treatment in this family of new prevention tools.  This cost-effectiveness provides a good fiscal argument against under-funding HIV treatment as a way to cut costs.

Over-treatment vs. Under-treatment

Over-treatment refers to beginning Anti-Retroviral Treatment earlier than medically necessary to maintain the health of HIV positive patients, in order to reduce the risk of infection to potential future uninfected sex partners.  While Anti-Retroviral Treatment has many benefits, it is neither an easy regiment to follow nor without serious side effects.  Anti-Retroviral Treatment is a form of chemotherapy and we should stop pretending that it’s not.  Over-treatment transforms the HIV positive from an agent controlling his own health to a mere vector of HIV transmission, with an implicit assumption that preventing the infection of the uninfected has greater value than maintaining the health of HIV positives.

Under-treatment occurs when HIV infected people do not know their accurate HIV status (the Unaware Infected), or are not linked to care (the Untreated Infected).  Recently, a new type of under-treatment has appeared.  As a result of the fiscal crises brought on by prolonged wars, irresponsible tax cuts, exorbitant drug prices and the “great recession”, HIV positives needing treatment are loosing access to Anti-Retroviral Treatment (the Defunded Infected): those on ADAP waiting lists (8,000 and growing as of May 2011) and those affected by manipulating eligibility thresholds to reduce the number eligible for funded treatment. 

Test and Treat is the most commonly used label for this process.  In an effort to minimize the danger of over-treatment, researchers developed a version of Test and Treat called Test & Link to Care which emphasizes bringing more people into care.  As Test and Treat is the more commonly used term, I have used the term, Test and Treat throughout to include Test & Link to Care.  For more information on Test and Link to Care, see Project Inform’s website 

Individual Level vs. Community Level

When most of us think about HIV preventions, we tend to think of individual level interventions, such as using condoms.  In these individual level interventions, we can easily identify those who will benefit from this intervention -- those people who use condoms.  Community level interventions differ in that we know that some people will benefit but we can’t predict who they will be.  Reducing HIV viral load at the community level is like fluoridating water to reduce the risk of tooth decay (community level) but using condoms is like brushing and flossing (individual level).  Fluoridated water does not reduce the need to brush and floss, but no individual level health intervention results in 100% adherence by all people all the time.  Fluoridated water provides protection for those times when people don’t brush or floss.  Community level interventions can compensate for individual level adherence failure.

Viral Load and Risk

The infection potential of any given action depends on the interaction between the infected person and the uninfected person.  The amount of viral material, that the infected person carries, affects risk level.  For HIV transmission to occur in any given sexual activity, the amount of viral material in the infected person’s semen or blood must exceed a minimal, threshold level for the particular sex act.  All animals have evolved barriers, such as the thickness of cell walls to protect the body from hostile microbes.  Consequently, the thickness and permeability of a cell wall depends on how frequently that part of the body comes in contact with the outside world or experiences trauma.  For infection to occur the infected person must have a viral load sufficient to penetrate the thickness of the cell walls in that portion of the uninfected person’s body that would come in contact with infected semen or blood.

Anal sex has most risk for HIV infection because less viral matter is necessary to produce an infection in this sex act due to the rectum’s relatively thin cell walls.  If the vagina had cell walls of similar thickness to the rectum, all women would bleed to death delivering their first child.  The cell walls in the mouth and throat evolved to be thicker to protect the bloodstream from infection during eating, drinking, and breathing.  The skin has the thickest cell walls as it has most frequent contact with germs, fungi, and bacteria.  For this reason, hand jobs have the least risk of HIV infection – unless the uninfected person’s hand has open cuts. 

An infected person’s saliva has relatively low amounts of the virus but his semen has relatively high amounts of the virus.  As the amount of viral material in an infected person’s saliva does not exceed the threshold level for oral transmission, kissing and sharing eating utensils cannot transmit HIV.  Anti-retroviral treatment reduces the amount of virus in the blood which, in turn, affects the amount in semen.  What matters is how much viral material is present in the semen at the moment of a sexual encounter, not at the moment of a lab test.  Few of us can afford an individual lab in their apartment, and fewer still would tolerate the “buzz kill” of lab tests immediately prior to sex, but researchers can average measures of individual viral load to estimate the viral load in the community.  Evidence from British Columbia, South Africa, and Switzerland support this relationship between decreased averaged community level viral load and reduced rates of new HIV infection.

Community Level Viral Load vs. Individual Level Viral Load

Averaged community level viral load differs from individual viral load tests.  A viral load test, like an HIV anti-body test, always refers to a past condition but infection only occurs in the present.  And a lot can happen between a viral load (or an HIV) test and the disclosure of its results.  An infection, such as syphilis, activates the immune system and increases the number of the cells that HIV targets (CD4s).  When these cells become available for viral infection and production, viral load dramatically increases.  HIV positives do have to be concerned about other STDs increasing their viral load and minimizing the benefits of treatment.  For these reasons a prior lab test showing undetectable individual level viral load does mean that condoms are unnecessary to reduce the risk of anal intercourse.  Reduced community level viral load will amplify, but not replace, the protective level of condom use in the event of breakage, incorrect use, or out-of-date condoms.

People have begun to argue that an undetectable viral load minimizes risk of infection to an acceptable level, but most of these discussions have ignored the risk of other STDs, such as syphilis.  In addition, like HIV negative sero-sorting, this argument ignores the credibility dimension of HIV status disclosure.  The critical components for the credibility of test results disclosure are 1) time since last test results, and 2) the source of the disclosure.  Older HIV or viral load test results (more than one month but less than one year) should generate decreased confidence.  Test results obtained more than one year ago should have no credibility.  The source of the disclosure can range from you boyfriend of years (high credibility) to an on-line profile (no credibility).  Given the general internet principle (“add at least 10 years, 20 pounds, and subtract 3 three inches”) about qualities that can be visually confirmed, it is difficult to understand why anyone would give any credibility to something as invisible as viral load or HIV status.  This argument needs to be further refined and debated before it can be fully accepted.

Reducing community level viral load

Reducing community level viral load by minimizing under-treatment requires bringing three distinct groups of people into care:  1) those who are unaware that they are HIV infected (the Unaware Infected), 2) those who know they are HIV infected but are not linked to care (the Out-of-Treatment Infected), and 3) those who would be in secure and accessible treatment if the political will to fully fund HIV treatment were present (the Defunded Infected). 

The Unaware Infected

These first three months of infection (the acute phase of HIV infection) have the highest levels of viral load and thus the greatest potential for infection.  If a guy tests regularly, but does not use condoms consistently for anal sex, that guy could become infected between regular HIV tests and incorrectly believe that he still negative.  More importantly, he may honestly, but inaccurately, tell potential partners that he is HIV negative, with serious consequences for HIV negative sero-sorting.  According to the National AIDS Strategy, about 20% of those infected lack awareness of their infection, but those more recently infected form an unknown portion of the Unaware Infected.  As the recently infected are more infectious, this group has greater likelihood of infecting others.  An increase in new infections will increase community level viral load, resulting in more highly infectious newly infected people who in turn increase the community level viral load, in a “snow ball” effect.  As positive HIV test has the effect of significantly reducing risk behavior, it is imperative to reduce the number of the Unaware Infected.

The Out-of-Treatment Infected

In a study published in AIDS (Marks, Gardner, Craw, and Crepaz, 2010), the authors reported that of those who test positive about 72% entered care within four months but only 59% remained in care.  This leaves 41% (the Out-of-Treatment Infected) of those currently aware of their HIV infection unable to test their individual level viral load on a regular basis.  Without regular viral load testing, a person cannot determine when, or if, to start anti-retroviral treatment.  Some of the Out-of-Treatment Infected will only access care when they develop full blown AIDS.  For these people, it’s still the 80s, except that it doesn’t have to be. 

The Defunded Infected

If treatment of HIV positives lowers the community level viral load, then denying people treatment, as in ADAP wait lists, will tend to increase the community level viral load, leading to to new infections.  A pharmacy assistance program exists in Florida, a state with the dubious honor of having half the people on the ADAP wait lists.  This probram has taken up much of the slack but people have to maintain current enrollment in two systems (ADAP and the Pharmacy Assistance Program), resulting in twice as many chances to be kicked off either system.  Furthermore, the pharmacy assistance program occurs at the discretion of profit seeking corporations.   It can stop at any moment.  A person prone to depression might easily give up on both systems.  This deliberate failure to provide consistent and accessible treatment for the infected has disastrous effects on preventing new infections.

Over-Treatment vs. Under-Treatment

Some people have expressed concern about how this could affect who benefits from treatment.  The drive to reduce community level viral load could influence the determination of when to begin treatment more than the responsibility to improve the health of the individual undergoing treatment (over-treatment).  Both the National HIV/AIDS Strategy and Test, and Test and Treat focus on bringing the under-treated into treatment.  While both stress the individual nature of the decision to start treatment, it is not at all clear whether the individual decision to start treatment is either a “decision” or “individual”.  In a doctor’s office, we are not equal.  Doctors have greater comfort and more knowledge than the stressed patient.  These conditions do not foster critical decision making.

If the National HIV/AIDS Strategy is implemented properly, however, we could easily tell if over-treatment or under-treatment is driving the lowering of community level viral load.  The National HIV/AIDS Strategy specifically identifies as outcomes to report:  1) decreases in the number of the Unaware Infected, 2) decreases in the number of Out-of-Treatment Infected, and decreases in the number of the Defunded Infected.  If viral load decreases, but the other factors fail to decrease or, worse, increase or if ADAP waiting lists continue, we would then have evidence that over-treatment is occurring and that the goals of the National AIDS strategy will not be met.  The exact formula and cut off point would have to be determined but it is entirely feasible.

In the current political-fiscal context, the dangers of under-treatment exceed the dangers of over-treatment.  All political trends emphasize increasing fiscal constraints.  “Pundits” have interpreted the 2010 mid-term elections as expressing concerns about the deficit, despite all indications that voters had more concerns about continued unemployment.  With the 2010 increase in GOP power in both the House and the Senate, demands for fiscal constraints will increase for all social programs, leading to increases in the Defunded Infected.  Under-treatment, not over-treatment of HIV, will continue to be the major problem, unless people mobilize successfully to defend and expand social programs. 

Test and Treat has dual benefits: increased quality and quantity of life for the infected and decreased risk of infection for the uninfected.  Combining prevention and treatment benefits makes them highly cost-effective, a useful argument in this era.  The other Treatment as Prevention tools (Post-Exposure Prophylaxis, Pre-Exposure Prophylaxis and Rectal Microbicides) use anti-retrovirals for individual prevention among HIV negatives.  Given the larger number of HIV negatives than HIV positives, these other tools could be very expensive.  It is difficult to understand how these other treatment as prevention tools could come on-line when there currently isn’t enough funding to treat the already infected. 

In addition, Test and Treat provides a cost-effective, measurable, way to increase the care for the HIV infected and to reduce the risk to the uninfected.  It has the potential to greatly increase access to HIV care for the most marginalized sectors of the infected.  While it will cost a great deal, it will cost considerably less than the Iraqi War.  Funds spent for HIV treatment, however will stay in the US.  More importantly by preventing new infections, it will save both lives and money in the long run.

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