A Cure for HIV?

Mural in Brussels

Here is a remarkable study by Sáez-Cirión and colleagues that was published this month in PLOS Pathogens. These authors looked at a group of 14 patients with HIV who received treatment early during infection and were able to maintain viral suppression even after coming off HIV medications. 

Historically, there has been controversy over when to start combined antiretroviral therapy (cART) for the treatment of HIV. Traditional arguments against starting cART early in infection included concern over possible long-term medication toxicity, cost and the development of drug-resistance. Arguments for early cART initiation include preserving immune function, reducing host viral reservoirs and limiting chronic immune activation. The study by Sáez-Cirión et al outlines another potential benefit: it is possible early therapy can lead to a "functional" HIV cure. 

Antiretrovirals have literally been life-saving to people living with HIV. Although these drugs suppress viral replication and allow for some amount of immune system recovery, in the vast majority of patients viral rebound and consequent immune system deterioration will occur rapidly once the drugs are removed. There are a small subset of patients (less than 1% of all HIV positive patients) who are, by virtue of gene differences, able to control the HIV virus to levels normally only achieved with cART (these patients are known as "HIV controllers"). 

Sáez-Cirión and colleagues examined a group of 14 patients who were discovered to have HIV very early in their infections and who were provided cART, and later came off cART. These patients behaved very much like "HIV controllers," although they did not have the gene distinctions that allow that group of patients to control HIV. As opposed to the typical scenario (where rebound viremia occurs quickly after cART cessation), these 14 patients demonstrated long-term viral suppression even off cART. These patients were dubbed "post-treatment controllers." The authors estimate that (among patients who are treated early in HIV infection) approximately 15% of patients receiving early HIV therapy may ultimately go on to have long-term viral suppression off cART. 

Although (early) post-treatment control of HIV does not truly represent a cure, for patients who benefit from this phenomenon this may represent a "functional" HIV cure. More study needs to go into this phenomenon and its implications for widespread HIV treatment and policy: will this phenomenon maintain over decades (not just years)? What are the implications of this for vaccine development? Certainly this implies that the immune system can be primed to efficiently control HIV: how can we capitalize on this via vaccination? How can we best identify patients with early HIV infection and get them into care immediately? What about the 85% of HIV positive patients who do not behave like post-treatment controllers?

The article by Sáez-Cirión and colleagues only further tips the scales in favor of early treatment. Antiretroviral drugs have become safer and easier to tolerate over the past decade, and as a result compliance with cART regimens has been easier to maintain. Recommendations for cART initiation have now fully shifted towards early therapy (see the most recent US national HIV treatment guidelines here), with therapy now recommended for all HIV positive patients regardless of immune status. With these new data implying that upwards of 15% of patients may be able to achieve a functional HIV cure with early cART initiation, identifying these patients early and getting them into care is more imperative than ever. 

The Dangers of Recreational HIV Drug Use: "Whoonga"

Here is an interesting NPR story of HIV drugs being used as recreational street drugs. Apparently this is a real problem in South Africa, although the issue has not generated a lot of press to date.

People crush anti-HIV drugs such as efavirenz and or ritonavir and mix these together with illicit substances (such as methamphetamine, opiates or marijuana) and smoke the concoction. In South Africa one such mixture is dubbed "whoonga").

Efavirenz can cause neuropsychiatric side effects (things such as vivid dreams). Ritonavir may boost the effect of other illicit substances.

A 2011 article on whoonga use from the BBC provides a nice overview of this problem in South Africa. A nice commentary piece published in the The Lancet Infectious Diseases on the recreational use of HIV drugs by Grelotti and colleagues (and on which the above NPR story was based) can be found here.

A major problem related to recreational HIV drug use is the emergence of anti-HIV drug resistance. HIV is a viral illness that requires multiple different anti-viral medications used in concert to treat effectively. When the virus is exposed to these drugs intermittently or not in combination drug resistance can emerge rapidly. Smoking "whoonga" essentially does just this: exposes people to intermittent levels of single anti-HIV drugs, thus allowing HIV to develop resistance to that single agent. This has serious consequences for the drug user if they are HIV positive, and to entire communities. If an HIV positive whoonga user develops efavirenz resistance, for instance, they can then pass that resistant virus on to another person.

In resource-limited settings sophisticated drug resistance testing is often not available, further complicating the ability to identify patients who have acquired resistance through recreational HIV drug use, or from contact with a recreational drug user.

The article by Grelotti and colleagues also outlines other potential consequences: diversion of HIV drugs, criminal behavior related to HIV drug diversion that can endanger patients and healthcare providers, et cetera. These authors call for more research into this issue and enhanced screening for recreational HIV drug use by clinicians.