Patient monitoring during HIV antiretroviral therapy

INTRODUCTION — Proper utilization of antiretroviral therapy (ART) requires ongoing patient monitoring to assess the therapeutic response and to identify adverse events related to chronic administration of medications. Failure to respond to a recommended ART regimen is almost always a result of suboptimal adherence or, less commonly, viral resistance.

This topic will focus on the approach to monitoring in patients receiving ART. Discussions related to selection and modification of ART, as well as primary care management of patients with human immunodeficiency virus (HIV), are found elsewhere. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load" and "Primary care of adults with HIV".)

FREQUENCY OF FOLLOW UP

Initial visit after starting ART — Most patients who are started on antiretroviral therapy (ART) should have follow-up within four weeks of starting treatment; however, earlier follow up may be needed for those with advanced HIV disease, especially if they are being treated for a concurrent opportunistic infection. (See "When to initiate antiretroviral therapy in persons with HIV", section on 'Patients with opportunistic infections'.)

We review the patient's understanding of their regimen (eg, if there are any drug or food interactions that impact how the regimen is administered) as well as their adherence to the regimen and any adverse effects. We also do laboratory testing to monitor the virologic and immunologic response and for evidence of toxicity. (See 'What to assess' below.)

Subsequent visits — After the initial visit, we typically see patients every three to six months, depending upon how they are tolerating their regimen and their virologic response. Once the patient is clinically stable on their regimen with viral suppression, visit frequency and laboratory testing can typically decrease to every six months thereafter. Some experts further reduce their visits to once yearly for select patients who have been stable for many years; however, this decision must be made on a case-by-case basis. (See 'Frequency of monitoring' below.)

Some patients may require a change in their regimen due to side effects, concern for toxicity, a desire to simplify their regimen, or virologic failure. Additional follow-up is typically needed in these settings. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load", section on 'Laboratory monitoring after regimen change' and 'Long-acting injectable therapy' below and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy", section on 'Viral load monitoring'.)

WHAT TO ASSESS — Patient monitoring in those receiving antiretroviral therapy (ART) primarily focuses on evaluating the efficacy (virologic and immunologic response) and the tolerability of the regimen as well as the patient's ability to take their medications as prescribed. Although immune activation and inflammation are thought to play an important role in the pathogenesis of certain long-term consequences of HIV infection (eg, non-AIDS-defining cancers, cardiovascular disease), these markers are not routinely monitored in clinical practice. (See "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV".)

Virologic response — Plasma HIV RNA should be measured in all patients at baseline and regularly during therapy since it is the most reliable indicator of response to ART and is useful in predicting clinical progression [1,2]. The goal of ART is viral load suppression below the limits of assay detection. The assays most commonly in use have lower limits of detection between 20 and 40 copies/mL. The time to achieve an undetectable viral load depends on the agents used in the regimen and the baseline viral load.

Definitions — When monitoring a patient's viral load on therapy, several terms are used. Clinicians should be proactive about defining what these terms mean to help avoid unnecessary anxiety and confusion when these terms are used.

●Virologic suppression – The term "virologic suppression" includes both a viral load that is "not detected" as well a viral load that is "detected, but is below the limit of quantification." The most commonly used assays have lower limits of detection between 20 and 40 copies/mL. (See "Techniques and interpretation of HIV-1 RNA quantitation", section on 'Laboratory methods for quantitation of HIV-1 RNA'.)

It is important to clarify these terms to avoid concerns about potential virologic failure or transmission risk if the viral load is detected below the level of quantification.

●Undetectable viral load – The term "undetectable" can have different meanings depending upon the context (risk of HIV transmission versus efficacy of HIV ART).

•In the context of reducing the risk of transmission to others (popularized as "U=U" or undetectable = untransmittable), "undetectable" refers to a viral load that is <200 copies/mL. In high quality clinical trials, HIV transmission has not been observed when individuals with HIV have a viral load <200 copies/mL [3-6]. (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention'.)

•However, for the purposes of monitoring the efficacy of ART, an undetectable viral load means that no virus is detected. (See "Techniques and interpretation of HIV-1 RNA quantitation", section on 'Interpretation'.)

In contrast to reducing the risk of transmission to others, persistent HIV RNA values below 200 copies/mL but above the lower limit of detection (ie, low-level viremia) may still indicate there is a potential risk of virologic failure. (See 'Approach to viral blips and persistent low-level viremia' below.)

●Viral blips – Viral "blips" refer to an isolated low-level of detectable HIV RNA, typically 20 to 200 copies/mL, that occurs during long-term monitoring of patients with a suppressed viral load on ART (ie, HIV RNA below the limits of assay detection) [7,8]. Viral blips are not uncommon and in themselves do not indicate a risk of virologic failure [9-11]. (See 'Approach to viral blips and persistent low-level viremia' below.)

●Persistent low-level viremia – Patients with persistent low-level viremia have persistent quantifiable viremia at a low copy count. We typically define persistent low-level viremia as a viral load between 20 and 200 copies/mL on two or more occasions spaced in time (generally more than one month apart). However, these terms are imprecisely defined in the literature, and HIV RNA values between 50 to 200, up to 500, or up to 1000 have variably been used as falling within this definition.

Patients with persistent low-level viremia likely represent a different population than those who experience a rare blip, described above. In addition, those with persistent low-level viremia may encompass two types of patients:

•Patients with optimal adherence – Patients with persistent low-level viremia despite optimal adherence typically have a high baseline viral load, representing a large HIV reservoir. In such patients, low-level viremia likely arises from periodic clonal expansion of long-lived cellular reservoirs of virus released into the blood and detected by viral load assays [12].

•Patients with intermittent adherence – In patients struggling with adherence, persistent low-level viremia may represent intermittent viral breakthrough due to subtherapeutic drug levels [13].

Studies evaluating the risk of resistance in patients with low-level viremia are conflicting. Although available data suggest most patients with low-level viremia do not develop resistance [14,15], some studies have demonstrated an increased risk of virologic failure compared to those with sustained viral suppression [16-18]. It is likely that patients with low-level viremia due to intermittent adherence would be most likely to have virologic failure.

●Virologic failure – We consider a patient to have virologic failure if they do not achieve a viral load <200 copies/mL within 24 weeks of initiating ART or if they have a sustained recurrence of viremia to >200 copies/mL (ie, on two consecutive measurements) after initial viral suppression.

This definition is consistent with the one used by the NIH AIDS Clinical Trials Group and the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents [7].

Frequency of monitoring

●Patients initiating ART – Our approach to virologic monitoring in patients initiating ART therapy is as follows:

•We perform HIV RNA testing approximately four weeks after initiating ART and then at four- to eight-week intervals until the level falls below the assay's limit of detection (<20 to 50 copies/mL by most commercial assays). Patients typically achieve viral suppression 8 to 12 weeks after ART initiation. (See 'Expected virologic response' below.)

•Once the viral load is below the level of detection, virologic monitoring can be performed every three to four months.

•If the viral load remains suppressed for one year, virologic monitoring can be reduced to every six months for those who are able to take their regimen as prescribed.

Patients who have a suboptimal decrease in viral load could be confused about how to take their regimen and/or be nonadherent. Thus, providers should talk with such patients to ensure they are taking their medications properly (eg, dosing, avoiding drug or food interactions) and counsel them on adherence.

Drug resistance testing should be performed on virus from patients who have not achieved HIV RNA suppression by 24 weeks, or earlier if there is a significant increase from a prior value. (See 'Virologic failure' below.)

●Patients switching regimens – For virologically suppressed individuals changing their ART regimen (eg, due to side effects or to reduce the risk of toxicity or frequency of dosing), HIV RNA should be monitored within two to eight weeks after a change is made to ensure viral suppression has been maintained [7]. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)

For patients receiving injectable therapy after a stable switch from an oral regimen, visit frequency depends on the dosing interval (monthly or every-other-month). We generally pair clinician visits with patients' scheduled injections and see patients one to two months after switching to injectable therapy (at their visit for their second injection) and then every six months, paired with an injection visit. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV".)

For those who switch regimens due to virologic failure, closer monitoring may be required. This is discussed in detail elsewhere. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy", section on 'Viral load monitoring'.)

Our approach to virologic monitoring is generally in agreement with United States Guidelines (The United States Department of Health and Human Services [DHHS] and The International Antiviral Society-USA [IAS-USA] panels) [7,19]. However, their recommendations for the frequency of monitoring vary slightly.

The DHHS Panel recommends HIV load testing at two to eight weeks after initiating ART and then every four to eight weeks after that until the viral load falls below the assay's limit of detection [7]. The viral load can then be measured every three to four months. The interval for viral load monitoring may be extended to every six months for adherent patients who have a suppressed viral load (ie, below the assay's level of detection) for more than a year.

The IAS-USA expert panel recommends measurement of plasma HIV RNA within the first six weeks of starting ART and every three months after treatment is initiated until a nondetectable viral load is confirmed [19]. The interval for viral load monitoring can be extended to every six months in patients with dependable adherence once the viral load has been suppressed for a year.

Expected virologic response — Patients initiating ART should achieve substantial (2 log or more) viral load declines by weeks two to four of treatment, with anything less than this suggestive of poor adherence. The viral load should be near or below the level of detection by 8 to 24 weeks, regardless of prior treatment experience, with patients who start with the highest viral loads taking the longest to reach this threshold [7,19-24].

The speed of the viral load decline depends primarily upon the agents used in the regimen [25-27]. The most rapid declines occur with integrase strand transfer inhibitor-based regimens; non-nucleoside reverse transcriptase inhibitor-based therapies are intermediate, and protease inhibitor treatments are the slowest.

Acute illness and vaccinations can cause a transient increase in the viral load. However, because of biologic variability, sequential HIV viral load measurements must exceed a threefold change or 0.5 log 10 copies/mL to be considered significantly different [7]. Unanticipated results should be verified with a repeat test before making changes in antiretroviral therapy.

Approach to viral blips and persistent low-level viremia — Viral blips and low-level viremia refer to low-levels of detectable HIV RNA, typically 20 to 200 copies/mL. These are defined in more detail above. (See 'Definitions' above.)

●Viral blips – Most viral blips are not clinically significant and are thought to represent laboratory variation or release of virions from the viral reservoir not related to active viral replication [28-30].

If a viral blip is detected in patients with long-term viral suppression, we initiate a discussion with the patient regarding adherence and medication reconciliation to assess for new drug/drug interactions (including over-the-counter medications).

If no concerning drug interactions are found and adherence is confirmed by self-report (and pharmacy refill information, if available), we simply repeat the test at the next scheduled monitoring visit. We do not modify antiretroviral treatment for patients who have a viral blip unless the viral load is sustained at >200 copies/mL, at which point we also recommend sending a resistance genotype. (See 'Virologic failure' below.)

In this era where patients may have immediate access to their laboratory results, it is helpful to counsel patients pre-emptively about the potential for viral blipping. While viral blipping may be important to the clinician as explained above, patients should be reassured that values between 20 and 200 in an adherent patient most often do not signify failure of a regimen and do not confer risk of transmission of HIV to others [3-6].

●Persistent low-level viremia – Patients with persistent low-level viremia have persistent quantifiable viremia at a low copy count. (See 'Definitions' above.)

Given the limited data in this population, there is no clear approach to management. Similar to those with a viral blip, we first assess adherence and drug-drug or drug-food interaction.

•If an adherence assessment confirms good medication adherence, and a careful medication reconciliation does not turn up significant interactions, the patient can be observed on treatment for a period of time as long as the viral load remains between 20 and 200 copies/mL.

•If the persistent low-level viremia extends beyond six months, it is reasonable to perform a genotype archive test to assess for archived resistance that may be playing a role. This test may be particularly helpful for those whose prior ART history is unclear. (See "Overview of HIV drug resistance testing assays".)

•If there is no evidence for concerning resistance mutations, we continue monitoring the patient on a routine schedule of every six months as described above. We do not intensify the existing regimen (ie, add an additional agent to the existing regimen).

If the patient is on a regimen with a low barrier to resistance (eg, elvitegravir-, raltegravir-, rilpivirine-containing regimens), we typically switch to a regimen that includes an agent with a high barrier to resistance (eg, bictegravir, dolutegravir, or a boosted protease inhibitor). However, there is no evidence that switching regimens in this setting leads to improved virologic outcomes, so it is also reasonable to continue monitoring the patient on their current regimen; decision-making should be made in discussion with patients.

Virologic failure — Virologic failure occurs when a patient is unable to achieve a viral load <200 copies/mL within 24 weeks of initiating ART or if they have a sustained recurrence of viremia to >200 copies/mL (ie, on two consecutive measurements) after initial viral suppression. (See 'Definitions' above.)

This definition is based upon the following rationale:

●There is no definitive evidence that patients with single viral loads quantified as >20 copies/mL and <200 copies/mL using current assays are at increased risk for virologic failure. (See 'Approach to viral blips and persistent low-level viremia' above.)

●This definition eliminates most cases of transient viremia caused by release of virus without viral replication or assay variability. (See 'Approach to viral blips and persistent low-level viremia' above.)

There are two main causes for virologic failure: drug resistance and/or subtherapeutic drug levels. The latter is almost always due to problems adhering to the drug regimen, with less common causes being drug interactions or altered pharmacology due to host factors (eg, malabsorption). Detailed discussions of the evaluation and management of patients with virologic failure are presented separately and summarized below. (See "Evaluation of the treatment-experienced patient failing HIV therapy" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)

CD4 count

Frequency of CD4 count monitoring

Our approach — The need for CD4 count monitoring after ART initiation depends upon the baseline CD4 count. This section summarizes our clinical approach. The recommendations of others are summarized below. (See 'Recommendations of others' below.)

●CD4 count >500 cells/microL – For patients who initiate ART at a CD4 count above 500 cells/microL, CD4 count monitoring is not needed if the viral load remains undetectable. While DHHS guidelines say that CD4 monitoring is optional after two years on ART with consistently suppressed viral load and a CD4 count >500 cells/microL, they note that data have not shown clinical benefit to monitoring at higher CD4 counts [7]. (See 'Recommendations of others' below.)

●CD4 count 300 to 500 cells/microL – For those who initiate ART with a CD4 count 300 to 500 cells/microL, we monitor the CD4 count every six months until the patient has been virologically suppressed for one year. After that, we monitor the CD4 count annually until it is >500 cells/microL, though it is also reasonable to stop monitoring CD4 count completely at this point. As stated above, CD4 count monitoring is optional for those with a CD4 >500 cells/microL.

●CD4 count <300 copies/microL – In patients with low baseline CD4 counts (eg, <300 cells/microL), we obtain a CD4 cell count three months after initiating therapy. Repeating the CD4 sooner is not indicated. Although the viral load decline occurs quickly due to the direct effect of antivirals, the CD4 rise is a slower process of innate immune reconstitution. Thus, a meaningful CD4 rise in that period of time may not be seen and should not affect clinical management. (See 'Expected CD4 response' below.)

We continue to monitor the CD4 count every three to six months until the CD4 count is ≥300 cells/microL. This allows us to assess immunologic recovery and the need for prophylaxis to prevent opportunistic infections. (See "Overview of prevention of opportunistic infections in patients with HIV".)

If the CD4 count remains ≥300 cells/microL on a stably suppressive ART regimen for at least a year, the frequency of testing can be reduced further. In this setting, we monitor the CD4 count annually until the CD4 count is >500 cells/microL; after that, CD4 count testing is optional. As outlined below in more detail, DHHS and IAS-USA guidelines differ on exact monitoring protocols. (See 'Recommendations of others' below.)

More frequent CD4 count monitoring (every three to six months) should be initiated (or reinitiated) in patients who are receiving immunosuppressive therapy as well as those who develop an opportunistic infection or have evidence of virologic failure. (See 'Virologic failure' above.)

Prior to the introduction of effective ART, CD4 counts were routinely monitored every three to six months. The use of less frequent CD4 cell count monitoring was supported in several studies. As an example, in a retrospective cohort study evaluating 832 patients with HIV receiving ART, those with an HIV RNA <200 copies/mL and a CD4 count ≥300 cells/microL had a nearly 100 percent probability of maintaining a CD4 count ≥200 cells/microL over four years when non-HIV causes of CD4 lymphopenia were excluded [31]. In an analysis of data from a prospective trial comparing different ART regimens, only 5 of 449 (1 percent) patients with an HIV RNA <400 copies/mL and a CD4 count >200 cells/microL after 48 weeks of treatment had a reduction in their CD4 count to <200 cells/microL [32].

Recommendations of others — In the United States, the IAS-USA and DHHS guidelines for CD4 monitoring differ slightly [7,19].

The IAS-USA states that once viral suppression is achieved in patients receiving ART, CD4 counts should be measured every six months until they are greater than 250 cells/microL for at least one year; after that, CD4 counts do not need to be measured unless there is evidence of virologic failure or the patient experiences an immunosuppressive condition [19].

By contrast, the DHHS guidelines recommend more frequent monitoring [7]. They state that for those with CD4 counts <300 cells/microL, the CD4 count should be repeated every three months for the first two years of suppressive ART; if CD4 count is ≥300 cells/microL, CD4 count testing should be performed every six months. After two years of suppressive ART, CD4 count monitoring can be reduced to every six months for patients whose CD4 counts remain <300 cells/microL and every year for patients whose CD4 counts are between 300 and 500 cells/microL. After two years, CD4 testing is optional for those with CD4 counts >500 cells/microL.

Expected CD4 response — CD4 cell counts correlate with the immune response. In patients who achieve and maintain viral suppression, immunologic improvement is progressive over many years [33].

Viral suppression is usually accompanied by an increase in CD4 count of ≥50 cells/microL at four to eight weeks, followed by slower incremental increases of 50 to 100 cells/microL per year [34]. The rate of increase in CD4 cells may be slower in older patients or in those with severe immunocompromise at baseline [35]. (See "HIV infection in older adults".)

CD4 cell counts may increase even in patients who cannot maintain viral suppression. These "discordant results" were seen most commonly in patients with extensive drug resistance to ART when fewer drug classes were available [36]. Various hypotheses for this observed immunologic benefit in the face of ongoing viremia have been proposed, including decreased replication capacity of resistant strains, decreased immune activation, and preservation of non-syncytium-inducing strains [37]. However, this immunologic benefit was usually lost when the HIV RNA returned to the pretreatment baseline [38]. With the current availability of a wide range of HIV treatments with activity against resistant viruses, most patients are able to achieve virologic suppression.

By contrast, rarely, patients may obtain viral suppression without any significant improvement in absolute CD4 cell counts, or paradoxically, even a decline [39]. Although the cause of this suboptimal CD4 response is usually not known, risk factors include advanced age and low nadir CD4 count. This observation has also been noted in patients with hepatitis C virus (HCV)-related cirrhosis and those treated with the combination of didanosine and tenofovir disoproxil fumarate, which is no longer recommended.

The CD4 count can be affected by inter-laboratory variability, acute illness, medications that suppress the bone marrow, and diurnal variation. For these reasons, results that are unexpectedly different from prior ones should be confirmed with a repeat test. A significant difference between two test results is generally defined as a 30 percent change in the absolute CD4 count or a change in CD4 cell count percent by three percentage points [7]. (See "Techniques and interpretation of measurement of the CD4 cell count in people with HIV".)

ART-associated toxicity — Patients receiving ART should be monitored clinically for side effects (eg, nausea, diarrhea). These side effects usually resolve on their own or with supportive care after a few doses. However, on rare occasion they can persist, and patients should be instructed to follow up with their clinician if resolution does not occur.

Laboratory tests should also be obtained at baseline and then periodically thereafter to monitor for toxicity related to ART. Hepatotoxicity and nephrotoxicity are rare but can occur, even in the absence of symptoms. Specific laboratory monitoring is outlined in the table (table 1).

If side effects or laboratory abnormalities are detected and persist, a change in the ART regimen may be required. As an example, a patient's renal function should be monitored using a creatinine-based estimated glomerular filtration rate; guidelines suggest substituting an alternative agent for tenofovir disoproxil fumarate if a patient has a decline in their estimated glomerular filtration rate (eg, by >25 percent and to a level <60 mL/min/1.73m²) and there are no other explanations for the decline [40]. More detailed information on switching regimens is presented elsewhere. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load", section on 'Reduced kidney function'.)

ART Adherence — Optimal adherence to an ART regimen (ie, taking all medication doses at the time intervals prescribed) is important to help patients achieve and maintain virologic suppression.

●Assessing adherence – At each visit, patients should be interviewed regarding medication adherence in a nonjudgmental manner. Adherence can vary over time and can be impacted by factors such as depression and substance use [41]. Although current antiretroviral medications are less affected by changes in adherence than treatments used in the early years of combination ART, it is still important that patients minimize missed doses.

In many patients, adherence can be difficult to assess. As an example, one study demonstrated that clinicians incorrectly predicted adherence in 41 percent of patients [42]. In addition, patients often exaggerate adherence to their provider. If adherence is uncertain (eg, a patient who endorses optimal adherence but has virologic failure), pharmacy records are useful to help track compliance when refills are obtained from a single pharmacy source.

If a patient appears to be missing doses on a regular basis, viral load testing should be performed. (See 'Virologic response' above.)

●Strategies to enhance adherence – To enhance adherence, patients should understand the link between adherence and drug resistance. (See "Interpretation of HIV drug resistance testing", section on 'Factors contributing to resistance'.)

In addition, it is useful to discuss medication schedules with patients to help them link pill-taking behaviors to other daily activities (eg, brushing teeth). If the patient admits to difficulties with adherence, potential barriers could involve the number and timing of doses, sizes of pills, food restrictions, stigma, and treatment-limiting side effects. The patient should also be advised to notify the provider if there is an anticipated problem with adherence, such as elective surgery or a prolonged intercurrent illness. (See "Overview of antiretroviral agents used to treat HIV".)

Whether and how injectable therapy may be an alternative treatment option for patients who struggle with adherence to daily oral therapy is being actively investigated. The currently approved injectable regimens of cabotegravir-rilpivirine have demonstrated efficacy in clinical trials as a stable switch from an oral regimen when the patient has an HIV viral load of <50 copies/mL. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV", section on 'Additional considerations'.)

Other adherence interventions (eg, assessing serum drug concentrations, monitoring pill counts, or use of electronic drug monitoring devices) are not routinely recommended in clinical practice [43]. Clinical trials have tried to assess whether directly observed therapy may improve virologic suppression rates. One meta-analysis of 12 studies suggested that such therapy seemed to offer no benefit over self-administered treatment [44]. However, directly observed therapy may be beneficial in patient subgroups that are at high risk for nonadherence, such as those who are homeless [45].

ADDITIONAL CONSIDERATIONS

Therapeutic drug monitoring — Therapeutic drug monitoring of antiretroviral agents is not routinely used in clinical practice [19]. Although there are a myriad of factors that can affect serum drug levels, including liver disease and plasma protein binding, these assays are not standardized and there are conflicting data on clinical utility.

Indications for changing therapy — Common indications for changing the antiretroviral regimen include:

●Virologic failure (see 'Virologic failure' above)

●Toxicity (see 'ART-associated toxicity' above)

●Intolerance

●Inconvenience or preference (eg, frequency of dosing, pill burden, or requirements for coadministration with food) (see 'ART Adherence' above)

The approach to changing regimens depends upon many factors, including the patient's viral load and is discussed in detail elsewhere. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load" and "Evaluation of the treatment-experienced patient failing HIV therapy" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)

Long-acting injectable therapy — A combination of cabotegravir and rilpivirine administered as an intramuscular injection is available for patients who are already undetectable and who have no known documented resistance to the component drugs. Additionally, lenacapavir has been approved as an injection every six months as part of a regimen for patients with resistant virus.

Visit frequency is dictated by the treatment regimen, and clinicians are encouraged to pair their clinician visits with patients with injection visits. A more detailed discussion of monitoring in patients receiving long-acting cabotegravir-rilpivirine is presented elsewhere. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV", section on 'Patient monitoring'.)

General medical care — Persons with HIV often require additional monitoring as part of routine medical care compared with other individuals of the same gender and age (table 1). This is discussed in detail elsewhere. (See "Primary care of adults with HIV".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV treatment in nonpregnant adults and adolescents".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: HIV/AIDS (The Basics)" and "Patient education: Tests to monitor HIV (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Goals of monitoring – Proper utilization of antiretroviral therapy (ART) requires ongoing patient monitoring to assess the therapeutic response and to identify adverse events related to chronic administration of medications. Failure to respond to a recommended ART regimen is almost always a result of suboptimal adherence or, less commonly, viral resistance. (See 'Introduction' above.)

●Frequency of follow up – Most patients who are started on ART should have follow-up within four weeks of starting treatment; however, earlier follow up may be needed for those with advanced HIV disease, especially if they are being treated for a concurrent opportunistic infection. (See 'Initial visit after starting ART' above.)

After the initial visit, we typically see patients every three to six months, depending upon how they are tolerating their regimen and their virologic response. Once the patient is clinically stable on their regimen with viral suppression, visit frequency and laboratory testing can typically decrease to every six months. (See 'Subsequent visits' above.)

●Virologic monitoring – Plasma HIV RNA should be measured in all patients at baseline and regularly during therapy since it is the most reliable indicator of response to ART and is useful in predicting clinical progression. The goal of ART is viral load suppression below the quantifiable limits of assay detection (eg, <20 to 40 copies/mL). (See 'Virologic response' above.)

•Frequency of testing – We perform HIV RNA testing approximately four weeks after initiating ART and then at four- to eight-week intervals until the level falls below the assay's limit of detection. Patients typically achieve viral suppression 8 to 12 weeks after ART initiation. (See 'Frequency of monitoring' above and 'Expected virologic response' above.)

Once the viral load is below the level of detection, virologic monitoring can be performed every three to four months. If the viral load remains suppressed for one year, virologic monitoring can be reduced to every six months for those who are able to take their regimen as prescribed. (See 'Frequency of monitoring' above.)

•Viral blips and persistent low-level viremia – Viral blips and low-level viremia refer to low-levels of detectable HIV RNA, typically 20 to 200 copies/mL. When low-level viremia is detected, we review adherence and drug-drug/drug-food interactions. In most cases, no further intervention is needed as low level-viremia is not usually associated with virologic failure. However, additional testing (eg, archived genotype) is reasonable if low-level viremia is persistent (eg, >6 months). (See 'Approach to viral blips and persistent low-level viremia' above.)

•Virologic failure – Virologic failure occurs when a patient is unable to achieve a viral load <200 copies/mL within 24 weeks of initiating ART or if they have a sustained recurrence of viremia to >200 copies/mL (ie, on two consecutive measurements) after initial viral suppression. The management of virologic failure is discussed in detail elsewhere. (See 'Virologic failure' above.)

●CD4 count monitoring – The approach to CD4 count monitoring after ART initiation depends upon the baseline CD4 count, and guideline panels differ in their approach. In patients with low baseline CD4 counts (eg, <300 cells/microL), we obtain a CD4 cell count three months after initiating therapy. We then continue to monitor the CD4 count every three to six months until the CD4 count is greater than 300 cells/microL. If the CD4 count remains >300 cells/microL on a stably suppressive ART regimen for at least a year, we monitor the CD4 count annually until the CD4 count is >500 cells/microL; after that, CD4 count testing is optional. (See 'CD4 count' above.)

●Adverse event monitoring – Patients receiving ART should be monitored for side effects (eg, nausea, diarrhea) and managed accordingly. In addition, laboratory tests should be obtained at baseline and then periodically thereafter to monitor for toxicity related to ART. Specific monitoring is outlined in the table (table 1). If side effects or laboratory abnormalities are detected and persist, a change in the ART regimen may be required. (See 'ART-associated toxicity' above.)

●Adherence monitoring – Optimal adherence to an ART regimen (ie, taking all medication doses at the time intervals prescribed) is important to help patients achieve and maintain virologic suppression. At each visit, patients should be interviewed regarding medication adherence in a nonjudgmental manner. Adherence can vary over time and can be impacted by factors such as depression and substance use. (See 'ART Adherence' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as author on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.