Infectious Diseases

Effect of Haart Resistance on HIV Treatment



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The introduction of Highly Active Antiretroviral Therapy (HAART), which meant prescribing multiple anti-HIV drugs at once rather than in sequence, was initially groundbreaking. Unfortunately, even with HAART, HIV-positive persons can and do still experience resistance to drugs eventually, and there is also a risk that new HIV-positive persons will already have a resistant variant of the virus. For this reason, medical researchers have long been experimenting both with new drugs to combat HIV, as well as new techniques to reduce viral resistance to medication.

HIV, the virus that causes AIDS, is transmitted through blood and sexual fluids and attacks the body's immune system. Eventually, after several years, the immune system becomes so thoroughly compromised by HIV that it begins to lose its ability to effectively combat other new infections. (The end state of the HIV illness, AIDS, refers to the period in which the immune system has become ineffective.) At that point, a person suffering from HIV is then at great risk from both common and unusual infections. Death from HIV occurs when a person falls prey to one or more of a number of these life-threatening opportunistic infections.

Although viruses are far more difficult to treat than bacteria, and although there is not yet a workable vaccine for HIV, for over two decades doctors have possessed antiretroviral drugs capable of checking an HIV infection. Until the advent of HAART, the problem with these drugs was that HIV very quickly developed resistance to them, often within a few months. At that point, the person taking the drugs would experience a resurging infection, quickly losing the partial restoration of their immune system health which the drug might have gained for them. HAART aimed to solve this by prescribing multiple different drugs at once. The logic was that the virus might develop a resistance to one drug, but was much less likely to develop a resistance to two, three or more drugs simultaneously. This logic was borne out in practice - leading to optimism that HIV might be on its way to becoming a chronic rather than terminal illness.

Unfortunately, even with HAART, resistance can and does occur eventually, although it takes much longer in some patients than others. Once the virus becomes immune to the drugs a person is taking, it will resume its unchecked progression through the body. At that point, while there is no active harm done by continuing the same treatment, there is also no further benefit, since the virus has become immune to the drugs. This is the reason that HIV-positive persons who are taking antiretroviral drugs are recommended to have their viral load tested on a regular basis: if the viral load spikes upward after a period of successful treatment, this is an indication that the drugs are no longer having the intended effect. It is also vital to take medications exactly as prescribed - missing doses or taking them contrary to instructions can reduce the potency of the drug and raise the risk of a new resistance emerging.

Once that occurs, the first and easiest option is to switch to a different set of drugs, against which the virus does not yet have any protection. Salvaging HIV treatment through second and subsequent rounds of treatment can be highly effective since, from the perspective of the virus, the new drugs are new and unfamiliar threats. Over time, however, resistance to these drugs can occur as well. People who have lived for many years with HIV may find that there are many anti-HIV medications which they can no longer use effectively. Essentially, providing that new drugs can effectively check HIV's progression, the treatment of HIV becomes a race between the virus, developing new mutations, and the pharmaceutical industry, developing new drugs. So long as researchers are ahead, patients usually will be, too.

Sometimes, however, there are simply no good alternative treatments available - or a person is reluctant to take on because of severe side effects. In such cases, even carefully managing a drug-free period, or "holiday," may be a useful part of treatment. If no drugs are being administered, then those copies of the virus with the genetic resistance to the drugs suddenly lose their survival advantage - and their numbers start to decline relative to other mutated copies of the virus. As a result, treatment with the same drugs can then resume in the future and regain some of its effectiveness, at least in the short term.

Ultimately, resistance to drugs is one of the most important potential consequences of HAART treatment. Antiretroviral drugs are proven to, in many cases, dramatically prolong the life of HIV-positive persons - but they can only do so as long as the virus does not become immune to the drug's effects.

- Sources and Further Reading -

The Body.com. "What is Resistance?"

James Learned. "Why HIV Drug Resistance Matters: An Overview."

Bob Munk. "Resistance to Anti-HIV Medications."

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