How HIV Is Treated

A Holistic Approach to Managing HIV Infection

Thanks to advances in treatment, people with human immunodeficiency virus (HIV) are living longer and healthier lives. This condition is chronic, yet it is manageable with treatment.

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Understanding HIV and AIDS

Survival with HIV requires that you maintain regular and consistent treatment. Only around 65% of the 1.2 million Americans who have 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, and only 56% will achieve the complete viral suppression that is needed to avoid disease progression.

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

As more and more T cells are destroyed, the immune system becomes weakened and can't effectively defend the body against infections. Without treatment, people with HIV will die from opportunistic infections, which are infections that a healthy immune system is normally able to control.

HIV is treated with a combination of antiretroviral drugs:

  • The first antiretroviral, AZT (zidovudine), was approved for use by the Food and Drug Administration (FDA) in 1987. Although AZT helped slow disease progression, 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.
  • By 1996, combination medications—referred to as highly active antiretroviral therapy (HAART)— reduced the HIV mortality rate by more than 50% in the United States and Europe. This treatment regimen could be complex, sometimes requiring 15 or more pills taken around the clock. Side effects could also be severe, in some cases causing irreversible peripheral neuropathy (nerve damage) and potentially disfiguring fat redistribution (lipodystrophy). And, drug resistance could develop rapidly if adherence was anything less than perfect.
  • Viread (tenofovir), approved in 2001 was able to overcome drug resistance, and it had once-daily dosing and fewer side effects than previously used drugs.
  • Recent advances 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. With today's treatment options, a newly infected 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 it reduces the effects of the infection, preventing the production of new HIV viruses in the body by blocking a stage in the virus's replication cycle.

Drug Classes

Antiretroviral drugs target specific stages of HIV replication, blocking enzymes or proteins that the virus needs to reproduce itself. Without the means to replicate, the HIV virus can be reduced to undetectable levels that can't severely harm to the body.

A sustained undetectable viral load prevents disease progression and also reduces the risk of infecting others.

There are currently seven classes of antiretroviral drugs. Of the seven stages of HIV replication, the available antiretrovirals target 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 translates viral RNA into DNA Emtriva (emtricitabine) Epivir (lamivudine) Retrovir (zidovudine) Viread (tenofovir) Ziagen (abacavir)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Reverse transcription Binds to the reverse transcriptase enzyme to prevent its action Edurant (rilpivirine) Intelence (etravirine) Pifeltra (doravirine) Sustiva (efavirenz) Viramine (nevirapine)
Integrase strand transfer inhibitors (INSTIs) Integration Blocks the integrase enzyme 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 Boosts the concentration of certain antiretrovirals so they work longer Norvir (ritonavir) Tybost (cobicistat)
Protease inhibitors (PIs) Assembly Blocks an enzyme called protease that promotes the building blocks that are used to assemble new HIV Aptivus (tipranavir) Lexiva (fosamprenavir) Prezista (darunavir) Reyataz (atazanavir)

Combination Therapies

Combination therapies are used to combat drug resistance and to block different stages of the virus' replication cycle.

The HIV virus has many 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.

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.

Studies have shown that once-daily, single-pill fixed-dose combination therapies improve adherence and 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 people who have 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 offers recommendations on how to treat HIV in adults, children, and pregnant people, and the use of pre-exposure prophylaxis (PrEP).

Starting Treatment

Their low risk of side effects, ease of use, and overall durability make integrase inhibitors the ideal drug for most people who are newly diagnosed with HIV.

The DHHS guidelines focus on drug efficacy and ease of use. In December 2019, the DHHS updated its treatment guidelines, reaffirming that integrase strand transfer inhibitors, or simply integrase inhibitors, are among the preferred drugs for the first-line treatment of HIV.

All five preferred first-line therapies include an integrase inhibitor as the backbone.

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 viral genetic mutations that cause drug resistance.

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

You can be infected with a drug-resistant strain of the virus, so genetic resistance testing is crucial.

Before you start therapy, 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 insufficient drug adherence.

If you have not had an adequate response to treatment, your doctor will again profile your virus to see which drugs it is 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.

Lifestyle

Managing HIV is about more than just pills. It's also important to manage any issues in your life that can affect your adherence or that could increase your risk of illness or infection.

Because you only see your doctor occasionally, it is up to you to manage your health. 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 one to three times a year to get your blood work checked and to have your results reviewed.

Keep your scheduled appointments so you won't have any gaps in your 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 updated on the latest HIV treatments and treatment guidelines.

General Health

HIV cannot be managed in isolation. It requires a holistic approach to avoid HIV-associated illnesses, as well as 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, occurring 10 to 15 years earlier than in the general population on average.

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 products 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 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. 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 if you are taking any antiretroviral therapy containing rilpivirine, as they can decrease the concentration of this HIV drug in the bloodstream. If you use them, 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, sometimes 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 symptoms 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. 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 may help manage chronic pain that's caused by peripheral neuropathy or 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. It can increase life expectancy and prevent the transmission of the virus to others. Treatment can 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 you need treatment, there are many federal, state, institutional, and pharmaceutical programs that can help pay for your treatment and care.

Frequently Asked Questions

  • How is HIV treated?

    HIV is treated with a combination of antiretroviral drugs. Antiretrovirals work by blocking different stages in the virus' life cycle to prevent the virus from making copies of itself that can go on to infect more of your immune cells.

  • What are the goals of HIV treatment?

    The primary goal is to reduce the viral population to undetectable levels. This prevents disease progression and dramatically reduces the risk of opportunistic infections and death.

  • How are HIV treatments chosen?

    HIV mutates continuously and has a multitude of variations, so a genetic resistance test can determine the characteristics of your virus and identify which antiretrovirals it is most susceptible to. The test may be accompanied by phenotyping, in which a sample of your virus is exposed to each antiretroviral to see which ones work best.

  • What happens if you stop HIV treatment?

    When you stop antiretroviral therapy, the viral number will rebound. In the end, antiretrovirals don’t kill HIV; they simply suppress the virus and keep it from destroying your immune system. If you stop and start treatment, the virus also has a greater chance of developing drug-resistant mutations, making your drugs less effective.

  • Are all antiretroviral therapies taken once daily?

    Until recently, that was the case. But in 2021, a once-monthly combination therapy called Cabenuva was approved by the FDA. The combination of two different injectable antiretrovirals, cabotegravir and rilpivirine, has proven to be just as effective in suppressing HIV as once-daily oral options.

  • What other treatments are used in people with HIV?

    For severely immunocompromised people, prophylactic (preventive) drugs may be prescribed to avoid opportunistic infections like toxoplasmosis, tuberculosis, pneumocystis pneumonia, and others. Vaccination for hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, pneumococcal disease, and shingles are recommended for everyone with HIV.

  • Can HIV be treated without antiretrovirals?

    No. Antiretrovirals are the only treatments that can block viral replication and prevent disease progression. There are no "immune boosters," supplements, or endorsed medical procedures that can "cure" HIV or alter the course of the disease in any way.

  • How long can you live if you are treated for HIV?

    If diagnosed and treated early, people with HIV can enjoy near-normal to normal life expectancy. Even people with advanced HIV can benefit from medication by preventing opportunistic infections.

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Article Sources
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