Treatment and transmission issues arising from HTPN 052

Early use of ART in trial 052 resulted in a 41% relative decrease in the number of serious HIV-related illnesses. This suggests that it is beneficial for people to start treatment when they have between 350 and 550 cells rather than delay initiation of treatment until CD4+ cells fall below the 250-cell mark.

Transmission issues

The study team calculated that there was a relative reduction of 96% in HIV transmissions because of the initiation of early ART.

Most transmissions (82%) occurred in participants who lived in Africa. This arose, in part, because of the large proportion of participants enrolled from that continent. Other factors that probably played a role in the high number of transmissions in African countries in trial 052 may have included:

• On average, viral loads in HIV-positive people in Africa tend to be greater than those in HIV-positive people from other regions; the reason for this difference in viral loads is not clear.
• The strain or subtype (also called clade) of HIV that is commonly found in Southern Africa, clade C, may be more easily sexually transmitted than other subtypes of HIV.

Other possible factors to account for the higher proportion of HIV infections in the African study sites, such as more frequent sex and less frequent use of condoms, are under investigation.

Infectious despite relatively high CD4+ cell counts

The researchers note that other studies have found that people with AIDS and those who have recently been infected with HIV are highly sexually infectious. However, they also stated in their report that the results from trial 052 and other studies “emphasize that HIV can be transmitted from infected persons who are asymptomatic or minimally symptomatic and who have high CD4+ counts. Since most persons with established HIV infection fall into the latter category, such transmission, albeit not maximally efficient, must help fuel the spread of HIV.”

Unfinished business

Researchers are still analyzing blood samples from four cases of transmission that occurred in the study. Investigation is still needed to find out why more transmissions occurred in Africa.

Unprotected anal sex is the most infectious sexual route for HIV transmission. We do not yet have details about the role that unprotected anal sex may have played in the transmission of HIV infections in trial 052.

Extending the benefits

Results from the present study clearly show that early initiation of ART in a population with a low rate of sexually transmitted infections (STIs) can greatly reduce the rate of HIV transmission to partners in stable, overwhelmingly heterosexual couples.

Although the results from trial 052 are greatly encouraging, as the proportion of MSM (men who have sex with men) couples in this trial was relatively small, firm conclusions cannot yet be drawn about the impact of ART on HIV transmission via unprotected anal sex among MSM.

The results from trial 052 support approaches commonly called “Test and Treat” or “Seek and Treat.” Such approaches applied at the level of a community or town or region with widespread HIV testing as part of a comprehensive HIV prevention package (testing, counselling, care) can lead to more diagnoses of HIV infection and offer early initiation of treatment. In such cases, early treatment helps preserve the health of the HIV-positive person and can help reduce the further spread of HIV in the community.

STIs

Sexually transmitted infections can cause inflammation on or inside delicate ano-genital tissue, providing an entryway for HIV. In trial 052, rates of STIs were relatively low and people were regularly screened and treated for STIs.

In the real world outside of a clinical trial, comprehensive programs are needed to extend the benefits of ART on HIV transmission to communities where HIV and STIs are common and people are at high risk for HIV infection. Such programs should include at least the following:

• regular counselling for serodiscordant couples about preventing HIV transmission, including the correct and consistent use of condoms
• regular counselling about taking ART exactly as directed and tips to maintain adherence
• advice about how to cope with the side effects and drug interactions that can occur with ART and other medicines commonly used by HIV-positive people
• regular screening for STIs
• treatment for diagnosed STIs

The role of ART in context

In an editorial that accompanied the publication of HTPN 052’s results in the New England Journal of Medicine, Dr. Scott Hammer from the Columbia University Medical Centre in New York City stated:

“Antiretroviral therapy is by no means perfect and is not the ultimate answer to controlling and ending the HIV epidemic. Adverse effects, emergence of drug-resistant viral strains, maintenance of adherence, sustainability, and cost are just some of the concerns.” However, “aggressive programs to diagnose and treat HIV infection as part of a comprehensive care package and multiple approaches to the prevention of HIV transmission that have been tested in well-designed clinical trials have the potential to preserve health and control the epidemic until a safe and effective HIV vaccine is a reality.”

—Sean R. Hosein

REFERENCES:

1. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493-505.
2. Hammer SM. Antiretroviral treatment as prevention. New England Journal of Medicine. 2011 Aug 11;365(6):561-2.
3. Goldsamt LA, Clatts MC, Parker MM, et al. Prevalence of sexually acquired antiretroviral drug resistance in a community sample of HIV-positive men who have sex with men in New York City. AIDS Patient Care & STDS. 2011 May;25(5):287-93.
4. Kalichman SC, Pellowski J, Turner C. Prevalence of sexually transmitted co-infections in people living with HIV/AIDS: systematic review with implications for using HIV treatments for prevention. Sexually Transmitted Infections. 2011 Apr;87(3):183-90.
5. Wilson DP, Grulich AE, Boyd M. Overly optimistic forecasts for the impact of treatment of HIV prevention for men who have sex with men. Clinical Infectious Diseases. 2011 Sep;53(6):611-2.