How HIV Is Treated

A Holistic Approach to Managing HIV Infection

Thanks to advances in treatment, people with HIV are living longer and healthier than ever. The newer classes of drugs are not only easier to take—often requiring only one pill daily—but also have far fewer side effects than drugs of the past and are more "forgiving" (meaning that you can miss the occasional dose without undue fear of drug resistance).

There are even therapies today that require once-monthly dosing.

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Understanding HIV and AIDS

Even so, only around 65% of the 1.2 million Americans living with HIV are on treatment, according to the U.S. Department of Health and Human Services. Of these, an estimated one in four will drop out of HIV-specific care, while only 56% will achieve complete viral suppression needed to avoid disease progression.

Still, this does little to detract from the genuine success of modern HIV therapy, which has transformed a disease that was once considered a death sentence into the chronic, manageable condition that it is today.

Fixed-dose combination antiretroviral drug Odefsey (emtricitabine, rilpivirine, tenofovir AF)
Fixed-dose combination antiretroviral drug Odefsey (emtricitabine, rilpivirine, tenofovir AF). Gilead Sciences

A Brief History

HIV is treated with a combination of antiretroviral drugs. The first such drug, called AZT (zidovudine), was approved for use by the Food and Drug Administration (FDA) back in 1987.

Although AZT helped slow the progression of the disease, resistance quickly developed, rendering the drug useless—often within the span of a year. Moreover, AZT could cause debilitating side effects like anemia and liver problems.

As drug development began to accelerate in the early- to mid-1990s, newer classes of antiretroviral were being introduced with increasingly promising results. By 1996, the combined use of these medications—referred to as HAART, or highly active antiretroviral therapy—proved to be the turning point in the pandemic.

Within two short years of its introduction, HAART reduced the HIV mortality rate by more than 50% in the United States and Europe.

Even so, treatment could be complex, sometimes requiring 15 or more pills taken around the clock. Side effects could also be severe, in some cases causing irreversible nerve pain (peripheral neuropathy) and potentially disfiguring fat redistribution (lipodystrophy). On top of that, drug resistance could develop rapidly if adherence was anything less than perfect.

The introduction of Viread (tenofovir) in 2001 is largely credited with turning things around. Not only was the drug able to overcome deep drug resistance, but it had far fewer side effects and helped usher in an era of once-daily dosing.

Recent advances in science have led to an increasing number of fixed-dose combination (FDC) drugs, many of which only require one pill daily. In January 2021, the FDA approved the first once-monthly therapy, called Cabenuva (cabotegravir + rilpivirine), which provides sustained viral control with two intramuscular injections.

Prior to the introduction of HAART, the average life expectancy for a newly infected 20-year-old was 17 years. Today, the same 20-year-old can live well into their 70s if diagnosed and treated early.

How Antiretrovirals Work

Antiretroviral therapy is the cornerstone of HIV treatment. It does not cure HIV but rather blocks (inhibits) a stage in the virus's replication cycle.

HIV causes disease by infecting a type of white blood cell called a CD4 T-cell that is central to the body's immune defense. Once HIV enters the cell, it "hijacks" its genetic machinery and turns it into an HIV-producing factory, churning out multiple copies of itself until the cell eventually dies.

As more and more of these cells are destroyed, the immune system becomes increasingly compromised and less able to defend the body against infections it could otherwise control. If left untreated, people with HIV typically die from these opportunistic infections.

Drug Classes

Antiretroviral drugs target specific stages of HIV replication, blocking enzymes or proteins that the virus needs to complete its life cycle. Without the means to replicate, the viral population is quickly reduced to undetectable levels where it can do the body little harm.

A sustained undetectable viral load not only prevents disease progression but also reduces the risk of infecting others to zero.

There are currently seven classes of antiretroviral drugs. Of the seven stages of HIV replication, the current body of antiretrovirals targets five.

Drug Class Stage(s) Blocked Drug Action Drugs
Entry/attachment inhibitors Viral attachment and fusion Prevents HIV from attaching to and entering the host cell Fuzeon (enfuvirtide)

Rubukio (fostemsavir)

Selzentry (maraviroc)

Trogarzo (ibalizumab)
Nucleoside reverse transcriptase inhibitors (NRTIs) Reverse transcription Blocks an enzyme called reverse transcriptase that translate viral RNA into DNA Emtriva (emtricitabine)

Epivir (lamivudine)

Retrovir (zidovudine)

Viread (tenofovir)

Ziagen (abacavir)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Reverse transcription Same as above but binds to the enzyme rather than blocking DNA assembly Edurant (rilpivirine)

Intelence (etravirine)

Pifeltra (doravirine)

Sustiva (efavirenz)

Viramine (nevirapine)
Integrase strand transfer inhibitors (INSTIs) Integration Blocks the enzyme integrase that the virus uses to integrate the newly formed DNA into the host cell's nucleus Isentress (raltegravir)

Tivicay (dolutegravir)

Vocabria (cabotegravir)
Pharmokinetic enhancers (a.k.a. "boosters") N/A Does not block any stage of replication but rather "boosts" the concentration of certain antiretrovirals so they work longer Norvir (ritonavir)

Tybost (cobicistat)
Protease inhibitors (PIs) Assembly Blocks an enzyme called protease that breaks down proteins into the building blocks used to assemble new HIV Aptivus (tipranavir)

Lexiva (fosamprenavir)

Prezista (darunavir)

Reyataz (atazanavir)

Combination Therapies

HIV is not one virus but a plethora of virus types (called variants). Because the viruses are churned out rapidly, the process of replication is prone to errors. As a result, the main virus type (called the "wild-type virus") will be accompanied by a multitude of variants, most of which are weak but some of which are drug-resistant.

To prevent disease progression, more than one antiretroviral is needed to block different stages of the replication cycle. If there is underlying resistance, one drug should be able to overcome it if the other drug can't.

If the drug resistance is severe, a larger combination of drugs may be needed to achieve viral suppression.

Historically, combination antiretroviral therapy consisted of a minimum of three drugs. Due to improved pharmacokinetics (drug activity), some combination therapies today require only two drugs.

In an effort to improve drug adherence, fixed-dose combination drugs are used whenever possible to reduce the overall pill burden. Studies have shown that once-daily, single-pill therapies not only improve adherence but reduce the risk of severe illnesses and hospitalizations.

There are currently 22 different fixed-dose combination antiretroviral drugs, some of which only require only one pill per day.

Brand Name Contents
Atripla 600mg efavirenz + 200mg emtricitabine + 300mg tenofovir disoproxil fumarate
Biktarvy 50mg bictegravir + 200mg emtricitabine + 25mg tenofovir alafenamide
Cabenuva 400-600mg cabotegravir + 600-900mg rilpivirine
Cimduo 300mg emtricitabine + 300mg tenofovir disoproxil fumarate
Combivir 300mg zidovudine + 150mg lamivudine
Complera 25mg rilpivirine + 200mg emtricitabine + 300mg tenofovir disoproxil fumarate
Descovy 200mg emtricitabine + 25mg tenofovir alafenamide
Delstrigo 100mg doravirine + 300mg lamivudine + 300mg tenofovir disoproxil fumarate
Dovato* 50mg dolutegravir + 300mg lamivudine
Epzicom 600mg abacavir + 300mg lamivudine
Evotaz 300mg atazanavir + 150mg cobicistat
Genvoya 150mg elvitegravir + 150mg cobicistat + 200mg emtricitabine + 10mg tenofovir alafenamide
Juluca 50mg dolutegravir + 25mg rilpivirine
Kaletra 200mg lopinavir + 50mg ritonavir
Odefsey 25mg rilpivirine + 200mg emtricitabine + 25mg tenofovir alafenamide
Prezcobix 800mg darunavir + 150mg cobicistat
Symtuza 800mg darunavir + 150mg cobicistat + 200mg emtricitabine + 10mg tenofovir alafenamide
Symfi 600mg efavirenz + 300mg lamivudine + 300mg tenofovir disoproxil fumarate
Symfi Lo 400mg efavirenz + 300mg lamivudine + 300mg tenofovir disoproxil fumarate
Stribild 150mg elvitegravir +150mg cobicistat + 200mg emtricitabine + 300mg tenofovir disoproxil fumarate
Triumeq 600mg abacavir + 50mg dolutegravir + 300 mg lamivudine
Truvada 200mg emtricitabine + 300mg tenofovir disoproxil fumarate

*Dovato is only approved for use in people with a viral load under 100,000.

Treatment Guidelines

The guidelines for use of antiretroviral drugs in the United States are overseen by the Department of Health and Human Services (DHHS). The DHHS panel of experts not only offers recommendations on how to treat HIV in adults and children but also how to prevent infection during pregnancy or through the use of pre-exposure prophylaxis (PrEP).

Starting Treatment

In December 2019, the DHHS updated its treatment guidelines, once again affirming that integrase strand transfer inhibitors, or simply integrase inhibitors, are among the preferred drugs for the first-line treatment of HIV.

In fact, all five preferred first-line therapies include an integrase inhibitor as the backbone. Their low risk of side effects, ease of use, and overal durability make integrase inhibitors the ideal drug for most people newly diagnosed with HIV.

The DHHS guidelines not only focus on drug efficacy but also on ease of use. As such, treatments with lower pill burdens are generally preferred over those with higher pill burdens.

DHHS Preferred First-Line Regimens (December 2019)
Option 1 Biktarvy (bictegravir + emtricitabine + tenofovir alafenamide
Option 2 Triumeq (abacavir + dolutegravir + lamivudine)
Option 3 Either: - Tivicay (dolutegravir) plus Descovy (emtricitabine + tenofovir alafenamide) - Tivicay (dolutegravir) plus Cimduo (lamivudine + tenofovir disoproxil fumarate)
Option 4 Either: - Isentress (raltegravir) plus Descovy (emtricitabine + tenofovir alafenamide) - Isentress (raltegravir) plus Cimduo (lamivudine + tenofovir disoproxil fumarate)
Option 5  Dovata (dolutegravir + lamivudine)

Prior to starting treatment, your doctor will order tests to "profile" your virus. This involves a blood test—referred to as genetic resistance testing—that identifies genetic mutations that confer resistance.

Based on the number and types of mutations you have, the lab can predict with a high degree of accuracy which drugs will work most effectively in you.

Because drug resistance can be transmitted—meaning passed from one person to the next through sex, shared needles, or other modes of transmission—genetic resistance testing is crucial even if you are newly infected.

In addition, your doctor will order a baseline CD4 count and viral load to track your response to treatment as well as other routine blood tests to monitor for any side effects.

Changing Treatment

Treatment failure, in which your drugs suddenly stop working, can occur naturally over time as mutations gradually develop. In most cases, however, treatment failure is the result of poor adherence.

Irrespective of the cause, your doctor will again want to profile your virus to see which drugs you are sensitive to. In addition to genetic resistance testing, another test—called phenotypic testing—may be ordered. This involves directly exposing the virus to all available antiretrovirals to see which ones work best.

Genetic resistance testing should ideally be performed while you are still on the failing therapy. If not, your wild-type virus will quickly recover and once again predominate, making it difficult to detect drug-resistant mutations.

Based on the results and recommendations from the DHHS, your doctor can select the best combination of drugs for you as an individual.

Lifestyle

Managing HIV is about more than just pills. It's about addressing issues in your life that can either influence adherence or place you at increased risk of illness or infection.

Because you only see your doctor occasionally, it is up to you to self-manage your disease over the long term. The choices you make can improve your outcomes.

Adherence

One of the key ways to ensure long-term adherence is to remain linked to HIV-specific care. This means seeing your doctor anywhere from one to three times a year to get your blood work checked and results reviewed.

By keeping your scheduled appointments, you are less likely to find yourself with an expired prescription and a gap in treatment.

While many general physicians and family practitioners are capable of overseeing your treatment, it often helps to see an infectious disease specialist, who may be better appraised of the latest treatments and treatment guidelines.

General Health

HIV cannot be managed in isolation. It requires a holistic approach to not only avoid HIV-associated illnesses but also non-HIV-associated illnesses that are the most common causes of death in people with HIV today.

In the United States today, people with HIV are more likely to die from heart disease, cancer, and liver disease than from HIV itself. Moreover, the risk of these diseases is higher among people with HIV than those without, with some occurring 10 to 15 years earlier than in the general population.

If you have HIV, you need to adhere to the same health recommendations as anyone else. This includes:

Over-the-Counter (OTC) Therapies

Over-the-counter (OTC) medications have no effect on HIV infection. Even though some manufacturers will market their product as "immune boosters," they ultimately do nothing to treat the infection or alter the course of the disease.

With that said, there are OTC medications and supplements that are sometimes used to relieve symptoms of the disease or side effects of treatment. These include:

  • Capsaicin: Topical and transdermal formulations of the chili-based medication are thought to relieve symptoms of peripheral neuropathy in some people.
  • Antioxidant supplements: Long-term HIV infection can increase the concentration of free radicals that cause harm to tissues and cells. There is some evidence, albeit scant, that antioxidant supplements like CoQ10 and L-carnitine may help neutralize free radicals (although there is no evidence that they can prevent or treat HIV-associated illnesses).
  • Calcium and vitamin D: Long-term HIV infection is also associated with bone mineral loss. Although it is unclear if calcium or vitamin D supplements can reduce the risk of HIV-associated hip pain and fractures, they may be a reasonable option for people with HIV who have osteoporosis or other conditions affecting bone mineral density.

The overuse of OTC supplements can often cause more harm than good in people. This includes the overuse of vitamin B6 (which can exacerbate peripheral neuropathy) and supplements like garlic and St. John's wort (which can affect the absorption of many HIV drugs).

Warning

Antacids should be used with caution in any antiretroviral therapy containing rilpivirine as they can decrease the concentration of the HIV drug in the bloodstream. If used, antacids should be taken at least two hours before or four hours after a rilpivirine dose.

Complementary and Alternative Medicine (CAM)

There are no complementary or alternative therapies that can take the place of antiretroviral therapy. With that said, many people with HIV will turn to alternative medicine to manage symptoms or treatment side effects.

Medical Marijuana

Medical marijuana has long been used to treat pain, reduce nausea, and stimulate appetite in people with HIV. Even so, the evidence remains lacking as to whether cannabis in any form offers therapeutic benefits.

However, a number of studies have shown that THC (the psychoactive ingredient of marijuana) may provide short-term relief of peripheral neuropathy when inhaled in a controlled dose.

There are drawbacks to use, including the possibility of addiction and the onset of respiratory problems. Moreover, state laws vary widely regarding the medical use of marijuana.

To avoid interactions and other possible harms, speak with your doctor before adding any complementary or alternative therapy to your treatment plan.

Yoga and Meditation

HIV is a disease characterized by high rates of stress, anxiety, and depression, particularly in communities where HIV is stigmatized. If left untreated, these emotions can affect a person's ability to seek or adhere to treatment.

Yoga, meditation, or any other mind-body therapy cannot overcome these issues on their own but may help manage stress and anxiety as part of an overall treatment plan.

Mindfulness-meditation has also been used to help manage chronic pain due to neuropathy, a practice that may have practical applications in people with peripheral neuropathy and other forms of chronic HIV-associated pain.

If you are experiencing severe depression or anxiety, do not hesitate to ask your doctor for a referral to a psychologist or psychiatrist who can offer counseling and medications, if needed.

A Word From Verywell

Without question, the benefits of HIV therapy outweigh the risks. Not only can it increase life expectancy and prevent the transmission of the virus to others, but it can also reduce the risk of severe HIV-associated and non-HIV-associated illness by as much as 72% if started early, according to research published in the New England Journal of Medicine.

HIV testing can be conducted confidentially. If treatment is needed, there are many federal, state, institutional, and pharmaceutical programs that can help pay for your treatment and care.

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