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When to initiate antiretroviral therapy in persons with HIV

When to initiate antiretroviral therapy in persons with HIV
Author:
Paul E Sax, MD
Section Editor:
Martin S Hirsch, MD
Deputy Editor:
Jennifer Mitty, MD, MPH
Literature review current through: Jan 2024.
This topic last updated: Mar 22, 2023.

INTRODUCTION — Epidemiologic data have demonstrated that combination antiretroviral therapy (ART) has led to remarkable declines in morbidity and mortality among persons with human immunodeficiency virus (HIV) [1-3]. Initially, there was a "hit hard and hit early" approach to treatment, implying that all patients should be treated with combination therapy as soon as possible [4]. Some providers, however, withheld therapy in patients with relatively preserved CD4 counts given the toxicity and complexity of early ART and the lack of clinical evidence proving a benefit of therapy for those with normal CD4 counts. Definitive clinical trials and further advances in HIV therapy have shifted the risk-benefit ratio back to earlier treatment. The standard of care today is to treat nearly all HIV-infected individuals with ART, regardless of CD4 count.

This topic will discuss when to initiate ART and will review the evidence supporting rapid initiation of therapy. The selection of specific medications and laboratory monitoring on treatment are discussed elsewhere. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Patient monitoring during HIV antiretroviral therapy".)

UNIVERSAL TREATMENT

Treatment regardless of CD4 count — We recommend antiretroviral therapy (ART) for patients with HIV infection and a detectable viral load, regardless of CD4 count. This approach is supported by guideline panels [5,6]. The benefits of ART are discussed below. (See 'Benefits of antiretroviral therapy' below.)

Considerations for treatment of HIV controllers, a small subset of patients who are able to maintain plasma HIV RNA at levels below the level of detection without ART, are discussed below. (See 'HIV controllers' below.)

Previous recommendations for ART in persons with low CD4 counts (eg, <350 cells/microL) were heavily influenced by drug toxicities, inconvenience, the potential risk for drug resistance if virologic suppression was not achieved, and limited treatment options for patients who failed therapy. Therapeutic options have now expanded, and the available agents are more potent, better tolerated, and associated with less toxicity compared with earlier agents. In addition, simplified regimens have led to improved adherence, which decreases the risk of developing virologic failure with drug-resistant virus. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Overview of antiretroviral agents used to treat HIV".)

Benefits of antiretroviral therapy — In persons with HIV, antiretroviral therapy (ART) reduces mortality as well as serious acquired immunodeficiency syndrome (AIDS)- and non-AIDS-related complications. Patients without other significant comorbidities who are treated before significant immunosuppression can expect a life expectancy approaching that of the general population [7,8]. Treatment also prevents transmission of HIV to others. (See 'Reduction in HIV transmission' below.)

Reduction in mortality and morbidity — For patients with HIV, effective ART results in sustained suppression of HIV RNA. This leads to improvements in cellular immunity (eg, CD4 count) and a subsequent reduction in AIDS-related morbidity and mortality. Suppression in HIV RNA can also result in a reduction in HIV immune activation (eg, proinflammatory cytokines, chronic inflammation, and T-cell activation), which can otherwise lead to end-organ damage (eg, coronary artery disease, liver and kidney disease, malignancy, neurologic disease) [9].

The benefit of ART for individuals with HIV, regardless of CD4 count or the presence of symptoms, was suggested by a large cohort study that described reduced mortality among those who received ART when the CD4 count was >500 cells/microL compared with starting treatment below this threshold [10]. Two large randomized clinical trials have subsequently supported this approach based upon favorable clinical outcomes without an increase in adverse events [11,12]. (See 'Patients with a CD4 count >350 cells/microL' below.)

However, the patient's baseline CD4 count can impact treatment outcomes. This was illustrated in a collaborative study of 62,760 treatment-naïve patients in Europe and the United States [13]. Over a mean follow-up of 3.3 years, 2039 patients died. Although the overall risk of mortality was reduced by approximately 50 percent among those who initiated ART compared with those who did not, the absolute survival benefit depended upon the patient's level of immunocompromise before treatment.

More detailed information on the benefits of ART is found below. (See 'Patients with a CD4 count ≤350 cells/microL' below and 'Patients with a CD4 count >350 cells/microL' below.)

Patients with a CD4 count ≤350 cells/microL — There is high-quality evidence that initiating ART in patients with a CD4 count ≤350 cells/microL results in a significant decline in the risk of AIDS-related morbidity and mortality [10,14-28].

In patients with AIDS (ie, a CD4 count <200 cells/microL and/or a history of an AIDS-defining illness), clinical trials have clearly demonstrated that ART improves survival and delays disease progression [16,28].

Initiating ART in patients with higher CD4 counts (before the CD4 count is <200 cells/microL) also reduces mortality in individuals with HIV. In a randomized clinical trial of 816 patients from Haiti, patients who initiated ART treatment when the CD4 count was <200 cells/microL had a higher mortality rate compared with those who initiated ART when the CD4 count was between 200 and 350 cells/microL (23 versus 6 deaths; hazard ratio [HR] 4; 95% CI 1.6-9.8) [26].

In patients with a CD4 count <350 cells/microL, the mortality benefit is mostly from a reduction in opportunistic and other infections.

Patients with a CD4 count >350 cells/microL — Initiating ART in patients with CD4 counts of >350 cells/microL reduces serious AIDS- and non-AIDS-related complications. The best evidence for initiating ART in patients with a CD4 count >350 cells/microL comes from the START and Temprano trials [11,12].

The START trial evaluated early versus deferred ART in 4685 treatment-naïve men and women with HIV who were from low-, moderate-, and high-income countries and had CD4 counts >500 cells/microL [11]. Individuals were randomly assigned to early initiation of ART (upon study entry) or delayed initiation (when the CD4 count reached 350 cells/microL). After approximately three years of follow-up, an interim analysis found the risk of a combined outcome that included AIDS-related events, serious non-AIDS events (eg, cancer, major cardiovascular, liver, and renal disease), or death was significantly reduced in individuals who received early compared with deferred therapy (1.8 versus 4.1 percent), leading to early termination of the deferred therapy arm. In both study groups, most events occurred when the CD4 count was >500 cells/microL (94 of 138 events). Compared with the group that was assigned to deferred therapy (median CD4 count 408 at ART initiation), the group that was assigned to early ART (median CD4 count 651 at ART initiation) was significantly less likely to develop serious AIDS- (HR 0.28; 95% CI 0.15-0.50) or non-AIDS-related events (HR 0.61; 95% CI 0.38-0.97).

The benefits of early ART were sustained over time, even after participants in the deferred therapy group were encouraged to initiate ART regardless of CD4 count [29]. During a median of 9.3 years of follow-up (from randomization through 2021), the risk of developing AIDS-related events, serious non-AIDS events, or death continued to be lower in the immediate versus deferred therapy group (HR 0.61; 95% CI, 0.49 to 0.76). Although the benefit of early ART diminished when all participants were offered ART (after January 1, 2016), there continued to be a lower number of adverse outcomes in the immediate therapy group (89 versus 113, respectively; HR 0.79 [95% CI, 0.60 to 1.04]). The continued benefit of early ART may be due in part to ongoing differences in immunologic recovery, as CD4 cell counts remained lower in the deferred therapy group (CD4 count difference 155 cells/microL from 2016 through 2021).

The TEMPRANO trial, which evaluated early versus deferred ART initiation (ie, at study entry versus World Health Organization criteria for ART initiation), enrolled 849 individuals with HIV from the Ivory Coast who had a CD4 count ≥500 cells/microL at study entry [12]. In both groups, the mean CD4 count at the onset of a primary endpoint (death from any cause, AIDS-defining disease, non-AIDS-defining cancer, or non-AIDS-defining invasive bacterial disease) was >500 cells/microL. However, individuals assigned to early therapy were significantly less likely to develop an event compared with those who were assigned to deferred therapy (HR 0.56; 95% CI 0.33-0.94).

Comorbid conditions — Among patients with HIV, serious non-AIDS events are more common and associated with higher rates of mortality than AIDS-related events [30,31]. Factors that independently predict death due to non-AIDS events include diabetes, advanced age, and hepatitis B/hepatitis C status.

ART has resulted in both a decreased incidence of HIV-related comorbid conditions and an improvement in the outcomes among those who develop disease. As examples:

Cardiovascular disease – HIV infection itself may accelerate atherosclerosis, and the incidence of coronary artery disease (eg, myocardial infarction [MI]) is higher in patients with HIV compared with patients without HIV who are matched for age and gender. Lower CD4 cell counts and higher HIV RNA levels have been associated with increased MI risk [32]. Although certain antiretroviral agents may be associated with an increased risk of MI (eg, abacavir, most protease inhibitors), most ART regimens do not increase the risk of MI, whereas untreated HIV does. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)

HIV-associated nephropathy (HIVAN) – Initiation of ART has been associated with a dramatic decline in the incidence of HIVAN. In addition, ART in patients with HIVAN has been associated with both preserved/improved renal function and prolonged survival. (See "HIV-associated nephropathy (HIVAN)", section on 'Antiretroviral therapy for all patients'.)

HIV-associated neurocognitive disorders (HAND) – Effective ART is the primary treatment of HAND. ART has been associated with improvement in cognitive function in certain patients and may prevent further impairment. (See "HIV-associated neurocognitive disorders: Management".)

Hepatitis B or C coinfection – HIV infection is associated with more rapid progression of viral hepatitis-related liver disease, including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and fatal hepatic failure. Progression of liver disease may be slower in such patients with hepatitis B or hepatitis C coinfection taking ART. In addition, in patients with HIV/HCV coinfection, ART is associated with reductions in nonopportunistic infection-related deaths [33,34]. (See "Treatment of chronic hepatitis B in patients with HIV" and "Treatment of chronic hepatitis C virus infection in the patient with HIV".)

Tuberculosis – ART reduces the risk of developing tuberculosis in patients with HIV, although incidence rates remain higher than in the general population. ART also improves treatment outcomes among those with tuberculosis in both resource-rich and resource-limited countries. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy" and "Diagnosis of pulmonary tuberculosis in adults".)

Malignancy – With the widespread introduction of ART, the incidence of Kaposi sarcoma and lymphoma has declined. Reductions in HIV viral load and improvements in immune function associated with ART have also been associated with improved clinical outcomes in patients with these tumors [35] and can result in an improved ability to tolerate chemotherapy and fewer opportunistic infections. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Treatment' and "HIV infection and malignancy: Epidemiology and pathogenesis" and "HIV infection and malignancy: Management considerations".)

The strongest evidence demonstrating a reduced risk of AIDS-related malignancy from early ART comes from the START study, described above [11]. In this study, there was a significant reduction in infection-related cancers (ie, those associated with human herpesvirus 8, Epstein-Barr virus, and human papillomavirus) among those receiving early ART (6 versus 23; HR 0.26, 95% CI 0.11-0.64) [36]. There was also a nonsignificant decrease in the risk of infection-unrelated cancers (8 versus 16; HR 0.49, 95% CI 0.21-1.15); however other data suggest that the rate of non-AIDS malignancies is stable or increasing [31].

Reduction in HIV transmission — In patients with virologic suppression on ART, the risk of sexual transmission to others is eliminated. For pregnant women, ART can prevent perinatal HIV transmission. Detailed discussions of the use of antiretroviral treatment to prevent HIV transmission are found elsewhere. (See "HIV infection: Risk factors and prevention strategies" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)

TIMING OF TREATMENT — For most individuals, we initiate antiretroviral therapy (ART) soon after their diagnosis. There are few reasons to delay ART when starting a tenofovir-based regimen with a high barrier to resistance. (See 'Approach for most patients' below.)

Special considerations in the following groups are discussed below:

(See 'Patients with acute symptomatic HIV infection' below.)

(See 'Patients with opportunistic infections' below.)

(See 'Pregnant persons' below.)

(See 'HIV controllers' below.)

Approach for most patients — For most patients, we suggest ART be prescribed within seven days of a confirmed HIV diagnosis, including on the same day, if feasible [5]. Rapid initiation of ART is associated with improved virologic outcomes and improved retention in care.

Treatments regimens for rapid ART initiation should be tenofovir-based and have a high barrier to resistance (eg, bictegravir-emtricitabine-tenofovir alafenamide, dolutegravir plus tenofovir alafenamide-emtricitabine, or pharmacologically boosted darunavir plus tenofovir alafenamide-emtricitabine). In this setting, ART can be initiated even if all baseline laboratory test results are not yet available (eg, basic metabolic panel, CD4 count, HIV resistance genotype, hepatitis B serology). By contrast, regimens that contain abacavir or non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens should not be used for rapid ART initiation if baseline testing is not available, since this information should be reviewed before one of these regimens is initiated. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Considerations prior to initiating treatment'.)

A brief delay in initiating ART is reasonable if there is concern for an active comorbid condition or an active opportunistic infection that makes starting ART difficult (eg, concerns for drug interactions or overlapping toxicity). However, most patients should initiate ART within two weeks of diagnosis. (See 'Patients with opportunistic infections' below.)

For patients who have barriers to taking daily therapy (eg, because of substance use disorder, depression, homelessness), we typically do not delay ART. In such patients, we initiate an ART regimen with a high barrier to developing resistance while addressing the specific adherence concerns.

In low- and middle-income countries, same-day initiation of ART has been associated with improved virologic outcomes and improved retention in care [37-39]. In a meta-analysis of rapid ART initiation within one week of diagnosis, including seven randomized studies with 18,011 participants, there was greater viral suppression (risk ratio [RR] 1.18; 95% CI 1.10-1.27) and better ART uptake (RR 1.09; 95% CI 1.06-1.12) at 12 months compared with standard of care [40]. In resource-rich environments, observational studies have demonstrated that same-day ART is feasible, safe, and can reduce time to virologic suppression by one to two months [41,42].

Although all populations can benefit from early ART, it is particularly important for patients with low CD4 counts (eg, a CD4 count ≤200 cells/microL). Such persons are at the greatest risk for AIDS-related complications, and delayed ART can lead to a suboptimal virologic and immunologic response to treatment [43-49]. (See 'Benefits of antiretroviral therapy' above.)

Considerations for specific populations

Patients with acute symptomatic HIV infection — For patients with acute symptomatic HIV infection, we initiate ART as soon as possible. If resources allow, initiation of ART on the same day of diagnosis can be a safe and effective treatment strategy. Early ART can decrease symptoms, preserve the CD4 count, and may reduce the size of the latent HIV reservoir. Treatment of patients with acute HIV also reduces the risk of transmitting HIV to others since early HIV infection is associated with high levels of HIV RNA and a corresponding high risk of viral transmission. A detailed discussion of the benefits of treatment in patients with acute HIV is found elsewhere. (See "Acute and early HIV infection: Treatment".)

Patients with opportunistic infections — The timing of ART in patients with opportunistic infections is influenced by the type of infection.

Approach for most opportunistic infections – ART should be initiated within two weeks for most opportunistic infections [5,6,50]. Early initiation of ART is effective in reducing mortality among patients who present with opportunistic infections [28,51-54]. This approach is best supported by the findings from a randomized trial in which 282 patients presenting with various opportunistic infections (two-thirds with Pneumocystis pneumonia) received "early ART" (initiated within 14 days of presentation) or "late ART" (initiated when opportunistic infection treatment was completed) [28]. Early treatment led to a 50 percent reduction in AIDS-related mortality without any increase in treatment-related adverse events or immune reconstitution inflammatory syndrome (IRIS).

Early ART is also important for the management of certain infections when specific anti-infective therapy is ineffective or only marginally effective (eg, progressive multifocal leukoencephalopathy, cryptosporidiosis). (See "Progressive multifocal leukoencephalopathy (PML): Treatment and prognosis" and "Cryptosporidiosis: Treatment and prevention".)

Patients with cryptococcal meningoencephalitis – In patients with cryptococcal meningoencephalitis, ART should be temporarily delayed since the benefits of early ART are outweighed by induction of a potentially serious IRIS. Trials comparing early versus delayed initiation of ART in patients undergoing treatment for cryptococcal meningoencephalitis consistently show improved survival with delayed initiation. A detailed discussion of when to initiate ART in this setting is presented elsewhere. (See "Cryptococcus neoformans meningoencephalitis in persons with HIV: Treatment and prevention", section on 'When to initiate antiretroviral therapy'.)

Other considerations – Some experts also delay ART in the setting of certain other opportunistic infections (eg, tuberculosis meningitis, pulmonary tuberculosis in patients with CD4 >50 cells/microL, coccidioidal meningitis) given the potential risk of IRIS and/or concerns for drug interactions that can lead to significant adverse events. However, the benefit of delaying ART in patients with these opportunistic infections has not been definitively established. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy" and "Management considerations, screening, and prevention of coccidioidomycosis in immunocompromised individuals and pregnant patients", section on 'Initiating antiretroviral therapy'.)

Additional discussions of when to initiate ART in patients with specific opportunistic infections are presented elsewhere. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Timing of ART initiation' and "Toxoplasmosis in patients with HIV", section on 'Antiretroviral therapy' and "Treatment of AIDS-related cytomegalovirus retinitis", section on 'When to initiate antiretroviral therapy' and "AIDS-related cytomegalovirus neurologic disease", section on 'When to initiate antiretroviral therapy'.)

Pregnant persons — ART is recommended for all pregnant persons with HIV to decrease the rate of perinatal HIV transmission and to treat the mother. The evidence for this recommendation, the timing of ART relative to stage of pregnancy, and the choice of agents that are safe in pregnancy are discussed elsewhere. (See "Prenatal evaluation of women with HIV in resource-rich settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)

HIV CONTROLLERS — A small subset of patients (≤0.5 percent) are able to maintain plasma HIV RNA at levels below the level of detection of standard HIV RNA assays without ART [55]. These patients are sometimes referred to as "HIV controllers." (See "The natural history and clinical features of HIV infection in adults and adolescents", section on 'HIV controllers'.)

For such patients, it is not clear if ART is beneficial, and we use a shared decision-making approach to determine if and when ART should be initiated. Patients who are concerned about the potential consequences of even very low-level viral replication and elevated immune activation may opt to start ART, whereas patients who are more concerned about taking a daily regimen and its possible adverse effects without certain benefit may reasonably defer treatment. To engage patients in decision-making, we discuss the following details:

There are data for increased immune activation, inflammation, and comorbidities in HIV controllers compared with individuals who have a suppressed HIV viral load on ART or individuals without HIV [56,57]. As an example, HIV controllers remain at increased risk for noninfectious complications of HIV, such as cardiovascular disease, compared with the seronegative population [57,58]. In addition, one analysis found an increased frequency of hospitalizations (especially hospitalizations for cardiovascular events) among HIV controllers as compared with individuals with HIV who were virologically suppressed on ART [59].

There are no comparative clinical trial data showing a clinical benefit of ART in HIV controllers, and the effect of ART on immune activation in this setting is unclear. In the START trial described above, which found a reduction in non-AIDS-related events in patients with a CD4 count >500 cells/microL [11], there were few HIV controllers, and there were no changes in markers of inflammation or CD4 count among those who initiated ART [60]. However, in a prospective study of 35 HIV controllers who initiated ART with rilpivirine-emtricitabine-tenofovir disoproxil fumarate, treatment reduced T-cell activation and improved markers of immune exhaustion [61]. ART also reduced the viral load as measured by an ultrasensitive assay and was associated with improved quality of life. In both of these studies, the number of HIV controllers was too small and/or the follow-up was too short to assess clinical outcomes.

Available antiretroviral drugs are more potent, more convenient, better tolerated, and associated with less toxicity compared with earlier agents, but ART is still associated with a small risk of bone, kidney, and/or other metabolic changes. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Commonly used agents' and "Overview of antiretroviral agents used to treat HIV".)

For those who do not initiate ART, regular monitoring of the CD4 counts and viral loads should be performed. ART should be started in those with decreasing CD4 counts or persistently detectable viremia. A subset of HIV controllers will experience HIV disease progression as evidenced by declining CD4 counts over time [56,62-64], and one small study demonstrated significant CD4 count increases after starting ART [65].

PATIENTS IN RESOURCE-LIMITED SETTINGS — The benefits of antiretroviral therapy (ART) have been demonstrated in widely divergent socioeconomic settings. Thus, indications for therapy do not generally differ in high- and low-resource regions. A discussion of when to initiate therapy in resource-limited settings is found elsewhere. (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings", section on 'Recommendations from the World Health Organization'.)

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 5th to 6th 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 10th to 12th 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: Starting treatment for HIV (The Basics)")

Beyond the Basics topic (See "Patient education: Initial treatment of HIV (Beyond the Basics)".)

SUMMARY AND RECOMMENDATIONS

Benefit of antiretroviral therapy – For nearly all persons with HIV, antiretroviral therapy (ART) improves clinical outcomes. Treatment results in sustained suppression of HIV RNA, improved cellular immunity (eg, CD4 count), reduced HIV immune activation (eg, proinflammatory cytokines, chronic inflammation, and T-cell activation), and decreased HIV transmission to others. (See 'Universal treatment' above.)

Who should initiate ART – We recommend ART for patients with HIV infection and a detectable viral load, regardless of CD4 count (Grade 1B). ART has been found to reduce serious AIDS- and non-AIDS-related complications in patients with a CD4 count >500 cells/microL. In addition, there is high-quality evidence that initiating ART in patients with a CD4 count ≤350 cells/microL results in a significant decline in AIDS-related mortality. (See 'Treatment regardless of CD4 count' above.)

Timing of treatment

For most patients – For most patients who are ready to start treatment, we suggest prescribing ART on the same day of the confirmed diagnosis or within seven days of diagnosis, even before the results of baseline laboratory tests are available (Grade 2C). Regimens used for same-day ART should typically be tenofovir-based and have a high barrier to resistance. (See 'Approach for most patients' above and 'Patients with acute symptomatic HIV infection' above.)

A brief delay in treatment is reasonable in patients who cannot take one of the above regimens, or if there is concern for an active comorbid condition or an active opportunistic infection that makes starting ART logistically difficult (eg, drug interactions or overlapping toxicity). However, most of these patients should initiate ART within two weeks of diagnosis. (See 'Approach for most patients' above.)

Selected opportunistic infections – Rarely, in the setting of specific opportunistic infections (eg, cryptococcal meningitis), treatment should be delayed longer than two weeks. (See 'Patients with opportunistic infections' above.)

Pregnant persons – For persons who are pregnant, the timing of ART initiation may depend in part upon the stage of pregnancy. This is discussed in detail elsewhere. (See "Prenatal evaluation of women with HIV in resource-rich settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)

HIV controllers – A small subset of patients, referred to as "HIV controllers," maintain plasma HIV RNA at levels that are below the level of detection of available assays without ART. For such patients, it is not clear if ART is beneficial, and we use a shared decision-making approach to determine if and when ART is initiated. Patients who are concerned about the potential consequences of even very low-level viral replication and elevated immune activation may opt to start ART, whereas patients who are more concerned about taking a daily regimen and its possible adverse effects without certain benefit may reasonably defer treatment. (See 'HIV controllers' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges John G Bartlett, MD, who contributed to an earlier version of this topic review.

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Topic 3777 Version 51.0

References

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