Three decades into the AIDS epidemic, advances in treatment have been astounding, turning a quick death sentence into a chronic manageable illness for those who have access to modern meds.
The HIV prevention story, however, hasn't been as happy. After a sharp drop in the late 1980s, the number of new infections in the U.S. reached a plateau, and holds steady at around 56,000 per year. Globally, there were an estimated 2.7 million new infections in 2008, and for every two people who start treatment, three more become HIV positive. Once-promising prevention tools such as vaccines and microbicides have seen very slow progress.
But what if HIV treatment itself is the best weapon against new infections? HIV medications dramatically lower the risk of transmitting the virus, and some experts think that if every person with HIV started treatment, transmission of the virus could finally be halted.
It is well known that lowering HIV viral load decreases the likelihood of transmission. This is already the standard approach for preventing mother-to-child transmission. Giving drugs like AZT or Viramune -- or even better, a combination regimen -- to an HIV-positive woman during pregnancy and delivery, and to the newborn immediately after birth, reduces the risk of the baby becoming infected to less than 2%. There's good reason to think a similar strategy would work for HIV transmission via sex or sharing drug injection equipment.
Early in 2008, the Swiss Federal Commission for HIV/AIDS set off a vigorous debate when it issued a report stating that a person taking HIV treatment with an undetectable viral load for at least six months and no other sexually transmitted diseases essentially cannot transmit HIV through heterosexual contact. The statement did not apply to gay men, who have not been studied as thoroughly as heterosexual couples.
At the 2008 International AIDS Conference in Mexico City, Commission President Pietro Vernazza explained that the statement was intended to aid Swiss physicians in discussing sexual risk with their patients, not as a universal recommendation. But he reaffirmed that unprotected sex with an HIV-positive person with undetectable viral load is as safe as using a condom -- not 100%, but within a "comfortable range" most people can live with.
This conclusion was based on several studies showing a very low likelihood of transmission between steady heterosexual partners. A study of nearly 400 mixed-status couples in Spain, for example, saw no new infections due to unprotected sex if the HIV-positive partner was taking treatment. A smaller Brazilian study found that transmission only occurred when the positive partner was not adherent to HIV therapy.
In June, the Partners in Prevention team reported in The Lancet that treatment reduced the risk of transmission between heterosexual partners by 92%. This study of more than 3,000 couples in Africa found that the transmission rate was very low (0.37 per 100 person-years). In contrast, 70% of new infections happened when the positive partner was not taking HIV meds and had a viral load over 50,000.
More cautious experts warn that, while HIV transmission may be rare when the positive partner is taking HIV drugs, it is not impossible. In the African study, there was one transmission from a positive partner taking treatment, and some other large surveys have also seen a very small number of similar cases. This may happen because even individuals on effective therapy can have viral load "blips," or brief increases. And a small proportion of people with an undetectable viral load in their blood can have persistent virus in their semen or vaginal secretions.
A concern is that people who think they cannot transmit HIV because their viral load is undetectable may dispense with safer sex or safer needle-use practices. If enough people do so, new infections could theoretically increase, even with a small risk of transmission.
Beyond prevention of individual infections, public health is a key issue underlying a more controversial approach known as "test-and-treat" or testing and linkage to care (TLC). The idea behind this strategy is that increasing the number of people who are taking HIV treatment lowers the "community viral load."
Viral load typically rises to a high level soon after infection and for the next few months. One study in Quebec found that as many as half of all HIV transmissions may happen during this time. Initial HIV infection often causes no symptoms -- or symptoms easily mistaken for the flu -- so most people do not know they are infected until they take an HIV test some time later.
Test-and-treat relies on regular HIV testing to catch each infection as soon as possible, followed by immediate treatment to minimize the time viral load is high enough to increase the risk of transmission. But everyone may not need treatment this early. Traditionally, explains Wafaa El-Sadr from Columbia University, it was assumed that after people acquire HIV they have "many, many years when they're infected but they're actually doing well, or they appear to be doing well."
But test-and-treat says don't wait to start treatment, and not just for public health reasons. While the benefits of early treatment for preventing HIV transmission are obvious, proponents argue that it has other advantages as well. A growing body of evidence shows that HIV causes persistent immune activation and inflammation that can contribute to problems throughout the body -- such as cardiovascular disease and brain impairment -- long before CD4 cells fall into the danger zone. What's more, today's meds are more convenient and more tolerable than earlier drugs and they can keep viral load low enough to stave off resistance.
In late 2009, a panel of HIV experts raised the U.S. guidelines for starting treatment from 350 to 500 CD4 cells; even above this level, half the panel favored treatment and half considered it "optional." Using a test-and-treat strategy, there would be no upper limit.
On the other side, people who oppose test-and-treat -- or who think it's premature -- say we really don't know how well the drugs will work and what kind of toxicities they might cause over the long term.
This poses a potential trade-off between individual and collective benefit. Why should people who do not yet need treatment for their own health take the risk of starting immediately to lower the odds of others becoming infected? HIV therapy is a lifelong commitment, and it may be hard for people to stick to it if they are basically healthy -- and less-than-perfect adherence can lead to drug resistance.
Some HIV advocates have additional reservations. Testing HIV positive and taking HIV drugs can lead to stigma, unwanted disclosure, problems with health insurance, legal consequences (especially around criminalization of HIV transmission), and even domestic violence. Further, there is concern about the possibility of mandatory testing or coercive treatment for the sake of public health goals.
The first support for test-and-treat as a public health strategy came from mathematical models, which plug different variables into equations to crank out predictions. At the 2006 International AIDS Conference, Julio Montaner and colleagues from the British Columbia Centre for Excellence in HIV/AIDS reported results from a "prevention-centered" model that looked at what would happen if all people with HIV worldwide started treatment, leading to no further infections thereafter.
The model showed that within 45 years, widespread treatment could reduce HIV transmission by 70-fold -- from more than 7 cases per 1,000 people to less than 0.1 cases -- and reduce the total number of people living with HIV from 38 million to less than 1 million. Assuming a generic regimen costing $1 per day, the total price tag would be $338 billion. That's a bargain compared to the $650 billion cost of the "current uptake" model, which assumed treatment coverage in low- and middle-income countries would reach the current level in wealthy countries.
"Although treating 100% of HIV-infected individuals worldwide might not be feasible or even ethically acceptable at this time, given the state of the pandemic, consideration of this possibility is worthwhile," the researchers concluded.
Taking financial and ethical barriers into account, Montaner's team devised a new mathematical model focusing on HIV-positive people in British Columbia who need treatment for their own health. If everyone started therapy when their CD4 count reached 350, they calculated that about 2/3 of new infections might be prevented by 2030. If just 75% started therapy, new infections would still decrease by 40%.
Reuben Granich and colleagues from the World Health Organization (WHO) presented another mathematical model in the January 3, 2009 issue of The Lancet. The researchers asked what would happen if all people age 15 and older in a high-prevalence area were voluntarily tested for HIV each year and if all those found to be positive started HIV treatment regardless of their CD4 count.
Using South Africa as a test case, and assuming that all transmission was via heterosexual sex, they estimated that a universal test-and-treat strategy could reduce new infections by about 95%, from 15-20 cases per 1,000 persons per year, to just one case, within ten years. Within 50 years, total HIV prevalence would fall to less than 1% -- essentially halting the epidemic. While the test-and-treat strategy would cost more up front, by 2032 its price tag would equal that of the current approach of limited testing and medically indicated treatment.
"Although other prevention strategies, alone or in combination, could substantially reduce HIV incidence," the WHO team concluded, "our model suggests that only universal voluntary testing and immediate initiation of antiretroviral drugs could reduce transmission to the point at which elimination might be feasible by 2020 for a generalized epidemic, such as that in South Africa."
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