How HIV Is Treated

In This Article

People with HIV are living longer and healthier than they have at any other time, thanks to advances in medicine. But ultimately, the treatment of HIV is about more than that. It's about understanding how the drugs work and identifying what you need to do as an individual to achieve the best positive results, whether you are newly infected or re-engaging with care.

The Evolution of HIV Treatment

There can be no doubt that the drugs used for the treatment of HIV have improved incredibly over the past decades. This is certainly true when compared to older generation agents that had higher rates of toxicity and were more prone to the early development of drug resistance.

Prior to 1996, when the first triple-drug therapy changed the very course of the pandemic, the average life expectancy for a newly infected 20-year-old male in the United States was a mere 17 years.

Today, newer generation therapies are able to afford life spans equal to that of the general population while boasting far fewer drug side effects and offering dosing schedules as simple as one pill per day.

Despite this, less than half of Americans receiving treatment are able to achieve the goals of therapy, due mainly to inconsistent dosing or voluntary treatment interruptions. More concerning yet is the fact that, of the 1.2 million Americans living with HIV today, and one out of eight have yet to be diagnosed.

Antiretroviral Therapy

Antiretroviral therapy (ART) is the cornerstone of HIV treatment. It's used to suppress the virus within the body, with the goal of bringing the virus to undetectable levels.

HIV is classified as a retrovirus, meaning that it replicates the opposite of how other viruses replicate. Rather than transcribing its genetic code from DNA to RNA, like most living organisms, HIV transcribes its code from RNA to DNA.

By identifying the mechanisms by which HIV replicates, scientists developed drugs—antiretrovirals—that are able to interrupt specific stages in the virus’s life cycle.

There are currently seven classes of antiretrovirals, each classified by the stage of the life cycle they inhibit:

HIV Life Cycle Stage What's Happening Corresponding Antiretroviral Drug Class Drug Examples
Attachment HIV attaches itself to a host cell. Fusion inhibitors (AKA entry inhibitors) Fuzeon (enfuvirtide, T20)
Fusion HIV fuses to the cellular membrane and deposits its genetic material into the host cell. Nucleoside reverse transcriptase inhibitors (NRTIs) Emtriva (emtricitabine)

Viread (tenofovir)

Ziagen (abacavir)
 
Reverse transcription The viral RNA is transcribed into DNA. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Edurant (rilpivirine)



Intelence (etravirine)




Sustiva (efavirenz)
Integration HIV’s DNA is integrated into the host cell’s nucleus, effectively hijacking the genetic machinery. Integrase inhibitors Tivicay (dolutegravir)

Vitekta (elvitegravir)
Transcription HIV uses that machinery to create the building blocks for new viruses. Protease inhibitors (PIs) Aptivus (tipranavir)

Kaletra (
Lopinavir/ritonavir)

Prezista (darunavir)
Assembly An immature virus is assembled and moved toward the surface of the host cell. Chemokine receptor antagonists (CCR5 antagonists) - a type of entry inhibitor Selzentry/Celsentri (maraviroc) 
Budding and maturation The virus literally buds from the host cell using the protease enzyme to create a fully mature virus Post-attachment inhibitors Trogarzo (ibalizumab)

Within these drug classes, there are 39 different antiretroviral drugs approved by the U.S. Food and Drug Administration (FDA). While highly effective, antiretroviral drugs do not eradicate the virus but rather impede its ability to replicate. By doing so, the immune system remains intact and is better able to fight diseases that can arise if immune defenses are compromised, which are known as opportunistic infections.

Pharmacokinetic enhancers also play an important part of HIV treatment. Pharmacokinetic enhancers aren't prescribed on their own, but rather alongside antiviral drugs to help increase their efficacy. Often referred to as "boosters," these drugs help slow the breakdown of antivirals, allowing for a lower dosage and therefore lessening side effects. Norvir (ritonavir) and Tybost (cobicistat) are both pharmacokinetic enhancers.

Combination Therapy

HIV is typically composed of a primary viral type (called the "wild type" virus) as well as a plethora of viral mutations, each with unique genetic signatures and conformations. A combination of antiretroviral drugs (which inhibit two or more stages of the life cycle) is used to suppress as many of these variants as possible to a point where a person’s viral load is considered undetectable.

When used in combination, antiretroviral drugs function as something of a biochemical "tag team." If drug A, for example, is unable to suppress a variant by suppressing a stage in the life cycle, then drug B and C can usually complete the job by attacking a different stage.

With this, HIV’s ability to replicate is almost completely stopped, with only a few mutant viruses able to escape and circulate freely in the bloodstream.

It's generally recommended that three different drugs from two different classes be prescribed. Genetic resistance testing is used by doctors to help identify the types and degrees of mutations that exist within your viral population, which helps them determine which combination of drugs is likely to work best for a specific situation.

The goal is not just to achieve viral control, but also overcome any drug-resistant mutations that may exist within the viral population.

Why Antiretrovirals Can't Cure HIV

A subset of the virus, called provirus, is able to embed itself in cells and tissues of the body known as latent reservoirs. Rather than replicating and emerging from infected cells, proviral HIV divides and replicates along with the host cell, undetected by the immune system. It can remain in this state for years and even decades, only to re-emerge when either treatment is stopped or proves ineffective.

Until scientists are able to "kick" the virus out of these hidden reservoirs and into body fluids, the ability of any agent to entirely eradicate HIV is unlikely, if not impossible.

Starting Antiretroviral Therapy

In May 2014, the U.S. Department of Health and Human Services (HHS) revised its HIV treatment guidelines, recommending the implementation of therapy in all adults diagnosed with HIV, irrespective of CD4 counts or stage of disease. In the past, treatment was only recommended when a person's CD4 count dropped below the threshold of 500 cells/mL.

The HHS decision was supported by evidence that early treatment is associated with a number of positive outcomes, namely:

  • A reduction in the risk of illnesses associated with HIV infection
  • A reduction in the risk of transmission from mother to child
  • A reduction in the risk of HIV transmission

The latter recommendation is further supported by evidence that antiretroviral therapy can significantly reduce the infectivity of a person living with HIV, a strategy known as treatment as prevention (or TasP). It has also been shown that people who are provided with early HIV therapy are 53% less likely to develop serious illness, both HIV- and non-HIV-related.

By contrast, deferring treatment until a person’s CD4 count drops below 200 (the stage of disease known as AIDS) can reduce that person's life expectancy by an average of 15 years.

Choosing Appropriate Drugs

The aim of first-line therapy is to prescribe the drugs that will provide the simplest dosing schedule, the fewest side effects, and lowest risk for the development of drug resistance. While treatment guidelines will regularly change and evolve with the release of new drugs or scientific information, the current body of science advocates the use of newer generation integrase inhibitors and nucleoside analogues in first-line therapy.

Among the 39 antiretrovirals approved by the FDA are 12 fixed-dose combinations (FDC) that contain two or more drugs. With these, you only have to take one pill (as opposed to several) daily, which can make following your treatment plan simpler.

Examples of fixed-dose combination drugs include:

  • Atripla (Sustiva, Viread, Emtriva)
  • Complera (Edurant, Viread, Emtriva)
  • Genvoya (Vitekta, Tybost, tenofovir alafenamide, Emtriva)
  • Odefsey (Edurant, tenofovir alafenamide, Emtriva)
  • Prezcobix (Prezista, Tybost)
  • Stribild (Vitekta, Tybost, Viread, Emtriva)
  • Triumeq (Ziagen, Epivir, Tivicay)
  • Truvada (Viread, Emtriva)

Keeping the treatment plan as simple as possible is particularly important since the current body of research suggests that people on treatment need to maintain greater than 90% adherence in order to achieve the optimal goals of therapy.

Taking your drugs exactly as prescribed, without missing any doses, is the best way to achieve the best results and minimize treatment failure.

If a Treatment Fails

Generally speaking, the duration of treatment efficacy is directly associated with the rate of adherence a person is able to achieve.

Failure to sustain viral control allows the virus to replicate freely, giving drug-resistant mutations the ability to thrive and become the predominant variant. When this happens, treatment will become less and less effective and eventually stop working altogether. This is known as treatment failure.

At this stage, doctors will need to perform genetic resistant testing to identify how extensive the drug resistance is. In some cases, resistance may affect only one or two drugs; in others, entire classes may be rendered ineffective. Treatment will then need to be revised to better overcome these issues while addressing the adherence barriers that may have caused the treatment failure in the first place.

Lifestyle

Diligent use of antiretrovirals is important. But a healthy lifestyle plays a big role in how you feel day-to-day, as well as how your disease is managed.

Stay Up-To-Date on Vaccines

HIV makes it harder for your body to fight infections. You can protect yourself from certain preventable diseases by staying up-to-date on your immunizations. Ask your doctor which vaccines are recommended for you.

Quit Smoking

Smoking when you have HIV has a huge impact on your health and can take years off of your life. Smoking is an unhealthy habit anyway, but its health ramifications hit people with HIV even harder, significantly raising your risk of lung cancer, heart attack, and stroke.

Moderate Your Alcohol Intake

Some studies have shown that alcohol intake may accelerate the progression of HIV, even while taking antiretrovirals. You may want to moderate your alcohol consumption. Talk to your doctor to see what is most appropriate for you, and especially if you feel you need help with your drinking.

Over-the-Counter (OTC) Therapies

Over-the-counter medications don't treat the virus itself, but are helpful in reducing certain troublesome symptoms and complications of the disease.

Among some options to consider:

  • Over-the-counter pain relievers like acetaminophen can help relieve headaches and body aches.
  • Topical capsaicin can be used for peripheral neuropathic pain.
  • Vitamin D and calcium: Antiretroviral therapy may cause a reduction in bone density, leaving you more at risk for developing osteoporosis. These supplements can help maintain bone strength.

Be careful with OTC antacids, as they can interact with antiretrovirals.

Complementary Alternative Medicine (CAM)

There are no CAM therapies that take the place of antiretroviral therapy. That said, many people with HIV turn to alternative medicine as a way to both manage symptoms of the disease and side effects of treatment medications. You should always talk to your doctor before adding anything to your treatment plan.

Yoga or Meditation

Yoga and meditation can help ease pain, as well as alleviate feelings of stress and depression that often come with an HIV diagnosis. An added benefit of yoga is that it is a gentle way to exercise.

Alpha Lipoic Acid

Although not widely studied for HIV pain, alpha lipoic acid has shown to improve diabetic nerve pain. As such, it may be helpful in managing neuropathic pain for those with HIV as well.

Medical Marijuana

Medical marijuana may help with pain, reduce nausea, and stimulate the appetite. There are drawbacks, though, including and the possibility of addiction. In addition, state laws vary widely when it comes to medical marijuana.

Herbal Supplements to Avoid

Although some herbal supplements are safe to use during treatment, others can interact with antiretrovirals. Because of this, certain herbs such as St. John's wort, garlic (supplements only, cooking with this herb is OK), ginkgo biloba, ginseng, kava kava, goldenseal, and evening primrose oil, should be avoided. This shouldn't be considered an exhaustive list; always talk to your doctor first before starting any herbal supplement.

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