Early Bird

Study results show immediate treatment holds promise as a prevention tool
by Chael Needle

Treatment and prevention make good bedfellows. That’s the idea underscoring the results of a large multinational clinical study, conducted by the HIV Prevention Trials Network, that looked at the risk of transmission in 1,763 serodiscordant (one partner is positive, one negative) couples, most of whom were male-female and whose risk factor was heterosexual sex.

Funded by NIAID, HPTN 052, as the randomized, multicenter study is known, looked at both immediate and delayed use of antiretroviral therapy in those living with HIV in relation to reducing transmission of HIV to their uninfected sexual partner. The study also looked at whether immediate inititation of antiretrovirals could benefit those who were HIV-positive. The couples in both arms received HIV-related primary care and counseling, including free condoms, treatment for STIs, regular HIV testing, and frequent evaluation and treatment for any HIV-related complications.

The Data and Safety Monitoring Board (DSMB), as independent reviewers of the study’s findings, found that immediate (and first-time) use of anti-HIV meds produced a ninety-six percent reduction in risk of HIV transmission among study participants. Those participants who were HIV-positive were required to have a CD4+ cell count between 350–500 cells/mm3 at enrollment. Starting the study back in 2006 and following guidelines that have since changed, researchers enrolled those who did not urgently need antiretroviral benefit (CD4+ cell counts below 250 cells/mm3 and/or having an AIDS-defining illness) in the immediate-use arm. The 350–500 T-cell count range is one at which starting treatment is now recommended, though still not deemed compulsory.

From this evidence, HPTN 052 researchers proclaimed that initiating antiretroviral therapy earlier could reduce transmission of HIV from the infected to the uninfected partner. Researchers also believe that this strongly shows that, for infected partners, suppressing the viral load makes one less infectious.

As for benefit of immediate use of antiretrovirals, the DSMB pointed to a statistically significant finding: Seventeen cases of extrapulmonary tuberculosis were noted among HIV-infected participants in the delayed treatment group compared to three cases in the immediate-use arm. However, even though a trend toward benefit was noted in the immediate-use arm, the difference between the two arms did not quite achieve statistical significance. For example, of the twenty-three deaths that occurred during the study, ten were in the immediate-use arm and thirteen were in the delayed-use arm. Researchers will have to analyze the data further to potentially enlarge the scope of these findings.

In an interview with A&U, Dr. Kathleen Squires, chair of the HIV Medicine Association (HIVMA) and director of the Division of Infectious Diseases at Thomas Jefferson University Hospital, highlighted the “double benefit” suggested by the immediate-use study findings: “protecting the individual’s health and protecting public health, if you will, by decreasing the risk for transmission.”

Representing the HIVMA, an organization of medical professionals practicing HIV medicine who advocate for HIV-positive patients, Dr. Squires says, “We see the findings as very compelling in terms of underpinning the 2006 CDC recommendations that HIV testing should be a routine part of medical care and that people who are HIV-infected should be started on therapy first and foremost for their own health….” Antiretroviral therapy, she suggests, has evolved into having a purpose beyond treatment, that is, prevention.

Part of the wisdom of the timing of when to go on treatment used to be that patients could protect themselves from side effects from antiretrovirals for some extent of time or defer the possible development of drug resistance. “For the individual, you certainly want to counsel about all the risks and benefits of therapy, but I think this study, as well as other observational studies, have dramatically demonstrated that antiretroviral therapy improves the health of the individual,” notes Dr. Squires. “Certainly at a time when we had much more intense regimens, meaning that you had to take multiple pills, multiple times per day, when some of the older antiretrovirals that we don’t use so much anymore had significant side effects, there was this feeling that you were sort of balancing the scales for therapy versus waiting. The mass of the data [now] really suggests that there is more risk to allow this infection to go on unchecked than to start antiretroviral therapy.”

With its demonstrated protective benefit, early therapy can now be used together with other preventative measures says Dr. Squires, about this intervention’s place in the so-called “prevention revolution” that some have been touting.

Thirty years into the pandemic, prevention is “an issue we’ve not conquered,” says Dr. Squires. “In the United States, for instance, we know we have a stable level of new infections over the past several years, about 56,000. So despite all of our prevention efforts we still see transmission at a very stable, and high, rate. So identifying people who are HIV-infected, first and foremost for their own health, but then also to use antiretroviral therapy in terms of cutting down on new transmissions. This data is compelling.”

Chael Needle wrote about Viramune XR in the May issue.

June 2011