Treatment as Prevention

Published - Written by John Staples

Kaplan–Meier estimates for the cumulative probabilities of linked HIV-1 transmission between partners

Just for a moment, imagine that you’ve just finished treating me for active pulmonary tuberculosis. I’m cured and therefore happy. What’s more, my future roommates are happy: I’ll no longer aerosolize inocula of acid-fast bacilli with each chesty cough, and they won’t even be exposed to the disease. Even my future roommates’ future roommates probably have cause to celebrate, and by treating me, you might have changed the course of the epidemic. Everyone wins.

Now let’s say I’m infected with the human immunodeficiency virus (HIV). There are plenty of medical, ethical, social, and economic reasons that you’d treat me with antiretroviral therapy. But would that treatment reduce the chance that I will pass the infection to someone else? With the results of the HTPN 052 trial, Dr. Myron Cohen (University of North Carolina at Chapel Hill) and colleagues answer that question with a resounding “Yes!”

The National Institutes of Health-funded HTPN 052 trial recruited 1763 couples from Botswana, Kenya, Malawi, South Africa, Zimbabwe, Brazil, India, Thailand, and the United States. The couples had to be in a stable sexual relationship, with one partner HIV-negative and one partner HIV-positive with a CD4 count of 350-500 cells/mm3. All couples were counseled to use barrier contraception methods to prevent HIV transmission. Half of the HIV-positive partners were randomly assigned to the standard-of-care ‘delayed therapy’ arm, in which antiretroviral treatment was initiated for HIV-related symptoms or a drop in the CD4 count below 350 cells/mm3. The other half of HIV-positive partners were randomized to immediate initiation of antiretroviral therapy regardless of CD4 count (the ‘early therapy’ arm). The primary endpoint was HIV transmission to the uninfected partner.

Did early treatment work as prevention? Yes, and dramatically so. The risk of virologically-linked HIV-1 transmission was reduced by an eye-popping 96% among couples randomized to early treatment (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). What’s more, HIV-positive individuals receiving early therapy were less likely to go on to develop the combined clinical endpoint of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.

In an accompanying editorial, Dr. Scott Hammer of Columbia University emphasizes that early HIV treatment appears to benefit both personal and public health, a nice “dovetailing” of aims. But questions remain. Are stable serodiscordant couples representative of the general population? What effect would this treatment strategy have on cost, adherence, and antiretroviral resistance? Would routine use of isoniazid prophylaxis against reactivation tuberculosis eliminate the individual benefits of early treatment? Will these results encourage the global community to reach out more generously to the 27 million HIV-infected individuals without access to antiretroviral therapy?

“The results of the HPTN 052 trial provide strong support for the treatment-as-prevention approach that we have long suspected might work on the basis of prior biologic and epidemiologic investigations,” says NEJM deputy editor and infectious disease specialist Dr. Lindsey Baden, “But how these results are best applied in the interest of clinical care and public health remains to be defined.”

For now, though, the results of HTPN 052 are a cause for substantial hope that the expansion of antiretroviral treatment programs might attenuate the ongoing HIV epidemic. If it does, everyone wins – and that’s a cause for celebration for us all.