Your Essential Guide to HIV Therapy

The 5 Most Frequently Asked Questions

Though recent advances in antiretroviral therapy have been nothing short of astonishing—affording people with HIV normal to near-normal life expectancy—there remain significant gaps in treatment among people living with HIV in the United States.

In fact, of the nearly 1.2 million Americans living with HIV today, fewer than one in four are able to achieve complete viral suppression, which is key to treatment success.

Hand holding a pill against a blue background
Gilead Sciences

This is a major problem. Without the means to achieve and sustain an undetectable viral load, people with HIV are at greater risk of HIV-related and non-HIV-related illnesses as well as the premature development of drug resistance.

Moreover, people with detectable viral loads are able to infect others. By contrast, a 2019 study in The Lancet concluded that people with an undetectable viral load have zero chance of infecting others.

In the end, HIV therapy is ultimately about more than just pills. It's about finding the tools to effectively manage your disease in partnership with your healthcare provider. It's about taking charge and normalizing HIV in your life so that you can control the disease rather than the disease controlling you.

It all starts with education and by asking yourself the right questions.

What Are Antiretrovirals?

Antiretroviral drugs do not cure HIV. Rather, they work by blocking a stage in the virus's replication cycle, either by binding to a protein or inhibiting an enzyme needed to complete the cycle. Without the means to do so, the virus will drop to undetectable levels where it can do the body little harm.

For antiretroviral therapy to work, several drugs are combined to block different stages of replication. To ensure that the concentration of medication in your blood remains at a steady state, you need to take the pills routinely and as prescribed (referred to as a treatment adherence).

When starting treatment, it is important to learn the names of your drugs—both the brand name (like Viramune) and the chemical name (like nevirapine)—and to ask your healthcare provider about possible side effects and drug interactions. By doing so, you can participate more actively in your treatment decisions and know when to act if a problem occurs.

There are over 40 antiretroviral drug options approved by the Food and Drug Administration, 13 of which are all-in-one combination tablets that require only one pill daily.

What Drugs Do I Start With?

A special panel organized by the U.S. Department of Health and Human Services oversees the HIV treatment guidelines in the United States. The group, comprised of healthcare providers, scientists, and public health officials, regularly updates their recommendations based on emerging science.

In most cases, a newer class of drugs called integrase inhibitors are included in the first-line treatment of HIV due to their efficacy, ease of use, durability, and low risk of side effects.

Even so, not everyone starts with the same drugs. Before prescribing treatment, your practitioner will perform tests to "profile" your virus and determine if it has any drug-resistant mutations that might limit the effectiveness of a drug. This typically involves a blood test referred to as genetic resistance testing.

Based on the findings and the DHHS recommendations, your healthcare provider can tailor treatment for you as an individual. In some rare cases, integrase inhibitors may not be a viable option and an alternative drug may be used.

Even if you are newly diagnosed, it is possible to have picked up a drug-resistant virus through sex, shared needles, or other modes of transmission. The phenomenon, known as transmitted resistance, is of growing concern among global health officials.

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What Causes HIV Resistance?

HIV drug resistance can develop naturally as your virus mutates in response to the medications you take. With that said, the resistance tends to develop slowly over the course of many years and requires multiple mutations before significant resistance occurs.

If drug resistance occurs early, such as within a year or two, it is more likely than not to be the result of poor adherence. Unless the virus is completely suppressed with uninterrupted therapy, drug-resistant variants can "escape" and gradually grow in numbers until they become the predominant type.

When this occurs, your drugs will not work as effectively. In some cases, the mutations you develop may even reduce the effectiveness of other antiretroviral drugs you've never been exposed to.

Other causes of premature resistance include HIV reinfection (wherein you may acquire a resistant virus), not adhering to food requirements (some medications need food to be absorbed), and drug interactions (which lower the concentration of an antiretroviral medication in your blood).

How Much Adherence Is Enough?

As a rule, people on antiretroviral therapy have long been advised to maintain greater than 95% adherence to sustain viral suppression. This translates to roughly 15 non-consecutive missed doses per year (or little more than one missed dose per month).

For some, this may seem a daunting task. But things have changed in recent years as more and more combination drugs are being released, allowing many people to take one pill daily rather than multiple drugs several times a day.

Single-pill therapies not only translate to improved adherence rates but also have been shown to significantly reduce the risk of severe illnesses and hospitalization compared to multi-pill antiretroviral therapy.

Furthermore, newer HIV drugs have improved pharmacokinetics (drug activity) and are more "forgiving," meaning that you can miss a dose without undue concern about resistance. Some studies have even shown that newer drugs like tenofovir and integrase inhibitors are able to sustain viral suppression with 85% adherence.

With that said, antiretroviral therapy consists of multiple drugs each with different half-lives, and adjusting the adherence threshold with each regimen is not only impractical but may end up causing excessive "slippage" in your routine pill-taking.

If you have problems with adherence, speak with your healthcare provider. While not everyone is a candidate for a one-pill option, there are other interventions your practitioner can use (including counseling, changes in diet, and automated reminders) to help overcome any barriers to adherence.

What Happens If A Treatment Fails?

When the drugs you take no longer work, you are said to have treatment failure. By definition, treatment failure is declared when you are unable to maintain a viral load of fewer than 200 copies per milliliter (mL) despite adherence to treatment. On top of that, the viral elevation must persist over several consecutive readings within the course of six months or sooner.

When failure is first suspected, your healthcare provider will assess whether you have any adherence problems and try to correct them in order to preserve the current treatment.

If that doesn't help, your practitioner will once again profile your virus. In addition to genetic resistance testing, your healthcare provider may order a phenotypic test in which the virus is directly exposed to all available antiretrovirals to see which ones work best.

Genetic resistance testing should ideally be performed while you are on failing therapy. If not, the original virus (called the "wild-type virus") can quickly grow and predominate once the treatment is stopped, making it difficult to identify the resistant variants.

A Word From Verywell

If you test positive for HIV, you need to start treatment as soon as possible. The longer you delay, the further your immune function can drop (as measured by the CD4 count). If the CD4 count drops below 200—the diagnostic definition of AIDS—your chances of complete immune recovery may also be decreased.

By starting treatment early, you not only stand a good chance of living a normal lifespan but will reduce your risk of serious HIV-associated and non-HIV-associated illness by more than half.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. What is the HIV care continuum?

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  4. U.S. Department of Health and Human Services. FDA-approved HIV medications.

  5. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Updated December 19, 2019.

  6. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Laboratory testing for initial assessment and monitoring of patients with HIV receiving antiretroviral therapy.

  7. Baxter JD, Dunn D, White E, et al. Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of Antiretroviral Treatment trial. HIV Med. 16(0 1):77-87. doi:10.1111/hiv.12236

  8. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Recognizing and managing antiretroviral treatment failure.

  9. Sutton SS, Hardin JW, Bramley TJ, D'Souze AO, Bennett CL. Single- versus multiple-tablet HIV regimens: Adherence and hospitalization risks. Am J Manag Care. 22(4):242-8.

  10. Kobin A, Sheth N. Levels of adherence required for virological suppression among newer antiretroviral medicationAnn Pharmacol. 45(3):372-9. doi:10.1345/aph.1P587

  11. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Management of the treatment-experienced patient.

  12. The INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 373:795-807 doi:10.1056/NEJMoa1506816

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.