by Roseann Vorce, Ph.D.,
Department of Pharmacology and Toxicology, Michigan State University
A report earlier this month describing a functional cure of HIV infection in a baby created quite a stir among scientists, health care workers, AIDS activists, and the general public. It was billed as the first time that HIV had been essentially eradicated from the body, giving hope to millions of people infected with HIV. As it turns out, a number of adults also have experienced a functional cure of HIV infection. In some ways, the functional cure of these HIV+ adults, termed post-treatment controllers, is more remarkable than is the functional cure of the infant.
As reported in the journal AIDS, 14 adults who had been infected with HIV have kept the virus under control for as long as 9.5 years after standard antiretroviral therapy was interrupted. The median time elapsed since therapy interruption was ~7.5 years, which is nearly 4x longer than the baby has remained HIV-free. In addition, the majority of these post-treatment controllers exhibited symptoms of infection prior to initiation of drug therapy, confirming that they truly had been infected with HIV. In contrast, some scientists remain skeptical that the baby truly had been infected with HIV, although several lines of evidence indicate that she harbored the virus. Researchers can find no sign of intact virus in the baby, whereas the adult post-treatment controllers retain low levels of intact virus. A few of the post-treatment controllers have experienced transient spikes in their viral loads. These temporary increases in detectable virus indicate that HIV can replicate, but the quick return to extremely low levels of virus confirm that the body can control the infection. Thus, the HIV status of these post-treatment controllers is different from that of the baby, although they share distinction of being functionally cured of HIV.
The authors of the AIDS article have explored several explanations for the ability of the post-treatment controllers to keep the virus in check. Although they have not determined a definitive answer, two major factors appear to be necessary, although not sufficient, to produce HIV control post-treatment: early treatment using a combination of antiretroviral drugs.
- Early antiretroviral therapy. All 14 patients started taking antiretroviral drugs during primary HIV infection; therapy was started within 10 weeks of infection. This early treatment appears to have restricted both the number and distribution of viral reservoirs in the body. In other words, combination antiretroviral therapy limited the places where HIV could hide.
- Combination antiretroviral therapy. Physicians had treated each of the 14 patients with a combination of antiretroviral drugs, including nucleoside reverse transcriptase inhibitors (e.g., zidovudine and lamivudine), non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine), and protease inhibitors. Most patients received drugs from two or more classes, but two patients received only two or three different nucleotide reverse transcriptase inhibitors.
As was the case of the baby cured of HIV, physicians had treated these post-treatment controllers using standard combination antiretroviral therapy; no new drugs or novel treatment protocols were used. Because this study was retrospective in nature, the treatment regimens of the post-treatment controllers differed. These differences make it almost impossible to identify relevant factors that contributed to the functional cure. In the future, carefully designed studies might enable researchers to develop a drug treatment protocol that maximizes the probability that patients will become post-treatment controllers. Hopefully, the right combination of drugs, administered during primary infection, at the right dose, and for the right duration, will increase the proportion of HIV+ patients who can control the virus without a lifetime of antiretroviral drugs.
- Sáez-Cirión A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard J-P, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C and the ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLOS Pathogens. 9, e1003211, 2013.
- Hocqueloux L, Prazuck T, Avettand-Fenoel V, Lafeuillade A, Cardon B, Viard J-P, and Rouzioux C. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS. 24:1598–1601, 2010.