ANTIRETROVIRAL THERAPY (ART)
Antiretroviral therapy involves taking a combination of HIV medicines every day. ART is recommended for everyone who has HIV and should be started as soon as possible. People on ART take a combination of HIV medicines every day, and initially the regimen generally includes three HIV medicines from at least two different HIV drug classes. ART cannot cure HIV, but HIV medicines help people with HIV live longer, healthier lives. ART also reduces the risk of HIV transmission.
Goals of HIV treatment are to:
- Reduce the viral load in the body to an undetectable level
- Reduce the risk of HIV transmission
- Prevent HIV from advancing to AIDS
- Protect the immune system
ART is recommended to be offered to all HIV-infected patients, including infants and children, even when they are asymptomatic, regardless of their immune status. For most patients, ART should be initiated soon after an initial diagnosis is made. Initiating ART at the first visit improves outcomes and adherence to care (HIV.gov, 2023c).
Types of Antiretroviral Medications
For most people, an ART regimen consists of a combination of these various classes of medications.
| Drug Class | Generic (Brand) Name |
|---|---|
| (HIV.gov, 2023c) | |
| Nucleoside reverse transcriptase inhibitors (NRTIs): inhibit transcription of viral RNA into DNA |
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| Non-nucleoside reverse transcriptase inhibitors (NNRTIs): inhibit transcription of viral RNA into DNA |
|
| Protease inhibitors (PIs): block an enzyme needed to make copies of the virus |
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| Fusion inhibitors (FIs): inhibit the binding and fusion with a CD4 cell |
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| Integrase inhibitors (INSTIs): inhibit an enzyme needed to make copies |
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| Chemokine receptor antagonists (CCR5 antagonists): inhibit entry into the cell |
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| Attachment inhibitors: inhibit entry into the cell |
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| Post-attachment inhibitors: block CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells |
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| Capsid inhibitors: interfere with replication |
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| Pharmacokinetic enhancers: increase effectiveness of an HIV medicine |
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Initiating ART
ART is recommended for all persons with HIV beginning as soon as possible following diagnosis to prevent complications of HIV, to reduce morbidity and mortality, and to prevent transmission of HIV to others.
Prior to initiation of ART, laboratory testing for drug resistance should be obtained. ART can be started, however, before test results are available.
Antiretroviral therapy is individualized and based on factors such as:
- Comorbid conditions, including cardiovascular disease, chemical dependency, liver disease, psychiatric disease, renal diseases, osteoporosis, tuberculosis, viral hepatitis
- Potential adverse drug effects
- Potential drug interactions with other medications
- Pregnancy or pregnancy potential
- Results of genotypic drug-resistance testing
- Specific tests regarding the medication to be considered
- Patient adherence potential
- Convenience (pill burden, dosing frequently, food and fluid considerations)
- Drug availability and cost
Initiation of therapy may be delayed due to certain opportunistic infections that may worsen clinically with commencement of ART, a condition known as immune reconstitution inflammatory syndrome (IRIS) (Bokhari, 2022).
ART Monitoring
Patients follow-up takes place within four weeks of starting treatment. At that time, laboratory testing is done to monitor the virologic and immunologic response.
After the initial visit, patients are typically seen every three to six months to assess for adherence and therapeutic response and to identify adverse events related to the chronic administration of these medications. Once the patient is clinically stable on their regimen with viral suppression, visit frequency and laboratory testing is typically done every six months.
Adherence Issues
Adherence to ART is a principal determinant of virologic suppression. Suboptimal adherence may include missed or late doses, treatment interruptions or discontinuations, and subtherapeutic or partial dosing. Poor adherence can result in a subtherapeutic plasma drug concentration, which may subsequently result in resistance to one or more drugs and cross-resistance to other drugs in the same class.
For each clinic visit, a routine adherence assessment is conducted. Viral loading is the most useful indicator of adherence and a routine component of monitoring individuals who are on ART. This evaluation assesses psychosocial and behavioral factors that may influence adherence, and interventions to help decrease such barriers should be supported.
Approaches to improve adherence address each person’s needs and barriers and might include:
- Discussing medication schedules to assist in pill-taking behaviors to link them to other daily activities (e.g., brushing teeth)
- Changing ART to simplify dosing or to reduce side effects
- Allowing flexible appointment scheduling
- Finding resources to assist with treatment cost to maintain uninterrupted access to both ART and appointments
- Linking patients to resources to assist with unmet social and economic needs, such as transportation, food, housing, and support services
- Linking patients to counseling to deal with stigma, substance use, or depression
Patients are advised to notify the provider if there is an anticipated issue with adherence, such as elective surgery or a prolonged illness (HIV.gov, 2023e; Gardland, 2023).
Antiretroviral Therapy Side Effects and Complications
Today’s HIV medications have fewer side effects, fewer people experience them, and they are less severe than in the past. Side effects can differ from person to person and depend on the type of medication. Some side effects occur at the start of taking a medication and may last only a few days or weeks, while other side effects begin later and last longer (HIV.gov, 2023e).
The focus of patient management is on individualized therapy to avoid long-term adverse effects. There are several factors that predispose patients to adverse effects, including:
- Concomitant use of medications with overlapping and additive toxicities
- Comorbid conditions that increase the risk of or exacerbate adverse effects, such as alcoholism or viral hepatitis
- Borderline or mild renal dysfunction, which increases risk of nephrotoxicity
- Drug-drug interactions
- Certain medications may exacerbate pre-existing psychiatric disorders
- Genetic factors that predispose patients to hypersensitivity reaction, neuropsychiatric toxicity QT interval prolongation, or hyperbilirubinemia
(HIV.gov, 2023e)
Indications for Changing ART Medication
On occasion, assessments find that the current regimen requires changing. Common reasons for changing the regimen include:
- Failure of the medication(s) to suppress viral load
- Adverse effects related to toxicity
- Intolerance to the medications
- Inconvenience or preference, such as frequency of dosing, pill burden, or requirements for co-administration with food
(Gardland, 2023)
DRUG RESISTANCE
HIV drug resistance is caused by mutations to the virus’s genetic structure that are slightly different from the original virus. As the virus multiplies in the body, it sometimes mutates. This can occur while a patient is taking HIV medications, leading to the development of drug-resistant HIV. Once drug resistance develops, the medications that controlled a patient’s HIV are no longer effective. HIV treatment failure results, and the person can transmit the virus to another individual, who will than have reduced treatments available.
Drug-resistance testing is done after HIV is diagnosed but before the person starts taking HIV medications in order to help determine which HIV medications are or are not to be included in the patient’s first HIV regimen. Once HIV treatment is started, a viral load test is used to monitor whether the medications are controlling the patient’s HIV. If testing indicates that the person’s HIV regimen is not effective, drug-resistance testing is repeated. These test results can identify whether drug resistance is the problem, and if so, they can be used to select a new regimen (HIV.gov., 2023e).