ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach

Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach
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 09, 2021.

INTRODUCTION — The treatment of human immunodeficiency virus (HIV) infection involves the use of combination antiretroviral therapy (ART). Use of these multidrug regimens substantially reduces progression to AIDS, opportunistic infections, hospitalizations, and death. Drug selection could potentially include more than 30 antiretroviral medications available in 5 major classes; however, only a small proportion of these agents are recommended for initial therapy.

This topic will address the general approach to choosing an initial ART regimen for treatment-naïve patients with HIV-1. Other topics relevant to the treatment of individuals with HIV include:

●(See "Treatment of HIV-2 infection".)

●(See "When to initiate antiretroviral therapy in persons with HIV".)

●(See "Patient monitoring during HIV antiretroviral therapy".)

●(See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)

●(See "Overview of antiretroviral agents used to treat HIV".)

●(See "HIV and women", section on 'Individuals of childbearing potential'.)

●(See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Integrase inhibitors'.)

●(See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings", section on 'ART selection and management'.)

●(See "Prevention of vertical HIV transmission in resource-limited settings", section on 'Maternal antiretroviral therapy'.)

GOALS OF THERAPY — The goals of antiretroviral therapy (ART) are to reduce HIV-related morbidity and mortality (from both infectious and noninfectious causes) and to prevent transmission of HIV to others. To achieve and sustain these goals, ART should result in maximal suppression of HIV RNA. Suppression of plasma viremia below the level of detection by commercial assays also prevents selection of drug-resistant mutations and allows for improved immunologic function (as measured by the CD4 cell count). A discussion on the use of ART for prevention of HIV transmission is found elsewhere. (See "HIV infection: Risk factors and prevention strategies".)

WHEN TO INITIATE ANTIRETROVIRAL THERAPY — Antiretroviral therapy (ART) should be offered to all persons with HIV, including asymptomatic individuals, regardless of their immune status [1,2]. The only individuals in whom the benefits of ART are not proven are the small proportion of untreated patients with preserved CD4 cell counts and undetectable HIV RNA (sometimes referred to as HIV controllers). (See "When to initiate antiretroviral therapy in persons with HIV".)

For most individuals, we initiate ART soon after their initial diagnosis. Initiating therapy at the initial visit can improve virologic outcomes and retention in care. However, there may be special considerations for patients with certain opportunistic infections or comorbid conditions. A detailed discussion of when to initiate therapy is presented in a separate topic review. (See "When to initiate antiretroviral therapy in persons with HIV", section on 'Timing of treatment'.)

ANTIRETROVIRAL AGENTS

Drug classes used in treatment-naïve patients — There are more than 30 antiretroviral medications from 5 major classes currently available for the management of patients with HIV (table 1). There are four classes of antiretroviral drugs typically used in initial regimens. These include:

●Nucleoside (and nucleotide) reverse transcriptase inhibitors (NRTIs)

●Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

●Protease inhibitors (PIs)

●Integrase strand transfer inhibitors (INSTIs)

The CCR5 antagonist (maraviroc) is also available, but it is not recommended for treatment-naïve patients. Other agents, such as the fusion inhibitor enfuvirtide, the attachment inhibitor fostemsavir, and the post-attachment inhibitor ibalizumab, are only recommended for patients with multidrug-resistant virus. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy", section on 'Fusion inhibitors' and "Overview of antiretroviral agents used to treat HIV".)

Commonly used agents — The most commonly used agents for treatment-naïve patients are summarized below and are described in greater detail elsewhere. (See "Overview of antiretroviral agents used to treat HIV".)

Special considerations regarding the use of these agents in pregnant women and women of childbearing potential are discussed in separate topic reviews. (See "HIV and women" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Prevention of vertical HIV transmission in resource-limited settings".)

●Nucleoside (and nucleotide) reverse transcriptase inhibitor (NRTI) combinations

•Tenofovir-emtricitabine – Tenofovir is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). The intracellular, pharmacologically active moiety is tenofovir-diphosphate, which is also active against hepatitis B virus. TDF and TAF are coformulated with emtricitabine, as well as several different third agents (table 1).

Tenofovir disoproxil fumarate-emtricitabine is very well tolerated, and a number of well-designed studies have found that this combination is effective in suppressing HIV RNA when used with a variety of different third agents [3-7]. However, TDF is associated with renal toxicity and should generally be avoided in patients with reduced kidney function (ie, estimated glomerular filtration rate [eGFR] <60 min/mL/1.73 m2). (See "Overview of antiretroviral agents used to treat HIV", section on 'Tenofovir'.)

Tenofovir alafenamide-emtricitabine became available in 2016. This agent has equivalent efficacy compared with tenofovir disoproxil fumarate-emtricitabine and improved renal and bone safety [8-12]. Unlike TDF, TAF can be used in most patients with moderately reduced kidney function [10]. (See "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions", section on 'Reduced kidney function'.)

However, TAF is associated with more weight gain than TDF [13,14], although this may be due to the weight-suppressive effect of TDF rather than a direct result of TAF [15]. In addition, TAF is more susceptible to drug interactions that induce its metabolism and should be avoided in patients taking certain medications, such as rifamycins and some anticonvulsants. Refer to the Lexicomp drug interaction program within UpToDate to assess for specific interactions.

•Abacavir-lamivudine – Abacavir-lamivudine is another NRTI combination that is commonly used. However, abacavir is contraindicated in persons who test positive for HLA-B*5701, as they are at high risk for developing an abacavir hypersensitivity reaction. (See "Abacavir hypersensitivity reaction".)

Although abacavir has less kidney and bone toxicity compared with TDF, there are concerns about its use in patients with high viral loads (unless dolutegravir is the third agent) and in those with or at risk for cardiovascular disease. (See "Overview of antiretroviral agents used to treat HIV", section on 'Abacavir' and "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions", section on 'Cardiovascular disease'.)

●Integrase strand transfer inhibitors (INSTIs) – For most patients, the INSTIs dolutegravir or bictegravir is included in one of the preferred regimens. These agents are well tolerated but may be associated with increased weight gain compared with other agents [13,16-18]. As an example, in one study that evaluated data from eight randomized trials, weight gain at 96 weeks in those receiving an INSTI, an NNRTI, or a PI was 3.2, 1.9, and 1.7 kg, respectively [13]. Among those taking an INSTI, weight gain was similar in those who received bictegravir- and dolutegravir-based regimens.

In general, there are relatively few drug-drug and drug-food interactions associated with dolutegravir and bictegravir, or the first drug in this class, raltegravir. By contrast, the INSTI elvitegravir must be given with cobicistat, a pharmacokinetic boosting agent that greatly increases drug interactions; hence, it is no longer considered a preferred agent. However, all INSTIs have an interaction with cation-containing compounds (eg, those that contain calcium, iron, or magnesium) requiring they be taken several hours apart or, in certain situations, together with food. Detailed information on management of drug-drug and drug-food interactions can be found in the Lexicomp drug interactions program within UpToDate and in a separate topic review. (See "Overview of antiretroviral agents used to treat HIV".)

Information regarding the specific INSTIs (in order of approval) used for treatment-naïve patients includes:

•Raltegravir – Raltegravir was approved for use in 2007, so among the INSTIs, there is the longest clinical experience with this agent. It also has the fewest drug-drug interactions in this class. For treatment-naïve patients, it can be administered as either one 400 mg pill twice daily (800 mg total daily dose) or as two 600 mg pills once daily (1200 mg total daily dose) [19]. Raltegravir is not coformulated as part of a single-pill regimen. (See "Overview of antiretroviral agents used to treat HIV", section on 'Raltegravir'.)

•Elvitegravir – Elvitegravir was approved in 2012 and is available as part of two coformulated single-pill tablets, elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide and elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate. The coformulation that contains TDF should only be administered if the eGFR is ≥70 mL/min/1.73 m2, whereas the TAF-containing formulation can be used in patients with an eGFR ≥30 mL/min/1.73 m2. (See "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions", section on 'Reduced kidney function'.)

Elvitegravir must be given with the pharmacologic boosting agent cobicistat for once-daily administration. Given this need for pharmacokinetic boosting, elvitegravir-containing regimens are associated with the greatest number of significant drug-drug interactions among the INSTIs. (See "Overview of antiretroviral agents used to treat HIV", section on 'Elvitegravir'.)

•Dolutegravir – Dolutegravir was approved in 2013. For treatment-naïve patients, it is given once daily and is available as a single agent or as a coformulated tablet (dolutegravir-abacavir-lamivudine, dolutegravir-lamivudine). Dolutegravir was noninferior to raltegravir in a comparative clinical trial in treatment-naïve patients [5] and is generally well tolerated.

Dolutegravir resistance is very uncommon, even in the setting of virologic failure, suggesting it has a higher barrier to resistance than raltegravir or elvitegravir. Thus, this agent is well suited for those who require treatment before the results of genotype testing are available or those who may have irregular adherence [1]. Additional reasons for using dolutegravir as a preferred third agent are described below. (See 'Approach for most patients' below.)

Despite the many advantages of dolutegravir, this agent has been associated with increased weight gain compared with other agents [13,16-18] and may have increased neuropsychiatric side effects compared with other INSTIs, although they do not typically lead to treatment discontinuation [20,21]. In addition, it has more drug interactions than raltegravir (eg, metformin, anti-epileptics) but far fewer than elvitegravir/cobicistat. (See "Overview of antiretroviral agents used to treat HIV", section on 'Dolutegravir'.)

•Bictegravir – Bictegravir was approved in 2018 as part of a fixed-dose, single-pill combination regimen (bictegravir-emtricitabine-tenofovir alafenamide). Resistance to this regimen has not been reported in clinical trials. Notable drug interactions include rifamycins and certain antiarrhythmic agents (eg, dofetilide). In two randomized trials in treatment-naïve patients, this regimen had similar efficacy to both dolutegravir plus tenofovir alafenamide-emtricitabine and dolutegravir-abacavir-lamivudine [22-25]. Bictegravir appears similar to dolutegravir in terms of weight gain [24]. (See "Overview of antiretroviral agents used to treat HIV", section on 'Bictegravir'.)

•Cabotegravir – The newest integrase inhibitor, cabotegravir, was approved for use in combination with rilpivirine and is available in an oral and a long-acting injectable formulation; however, this agent should only be used in virologically suppressed patients switching regimens. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV".)

●Protease inhibitors (PIs) – PIs are typically administered in combination with a nucleoside combination; however, they can also be used as part of a nucleoside-sparing/limiting regimen. PIs should be administered with a boosting agent such as ritonavir or cobicistat. Although boosted darunavir and boosted atazanavir are both effective as initial therapy in combination with nucleoside analogs, boosted darunavir is generally preferred because it is better tolerated. (See "Overview of antiretroviral agents used to treat HIV", section on 'Protease inhibitors (PIs)'.)

Some of the class side effects of PIs are hyperglycemia, diabetes, and hyperlipidemia. In addition, the need for pharmacological boosting can result in significant drug interactions. However, PIs have a high barrier to developing resistance, and therefore, they are sometimes chosen for patients who take their medications intermittently. (See 'Patients with adherence concerns' below.)

●Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – The NNRTIs are typically administered with a tenofovir-containing NRTI combination. For treatment-naïve patients, the most commonly used agents are efavirenz and rilpivirine. Doravirine, the newest NNRTI, was approved for use in the United States in 2018 [26].

Efavirenz had been the preferred third agent for many years, but it is now considered an alternative agent. Compared with the recommended INSTIs, efavirenz has an increased risk of side effects (eg, neurologic and psychiatric side effects) and a lower barrier to resistance. (See "Overview of antiretroviral agents used to treat HIV", section on 'Efavirenz'.)

Rilpivirine has a favorable lipid profile, small pill size, and is well tolerated. However, it is limited to patients with a with a baseline viral load <100,000 copies/mL and a CD4 count ≥200 cells/microL. In addition, rilpivirine must be administered with a meal, and concomitant use of rilpivirine with proton pump inhibitors is contraindicated. (See "Overview of antiretroviral agents used to treat HIV", section on 'Rilpivirine'.)

Doravirine was found to be noninferior to efavirenz- and darunavir-based regimens in randomized clinical trials [27,28]. It has fewer central nervous system side effects than efavirenz and better lipid profiles than both efavirenz and darunavir/ritonavir. However, there is limited experience with this agent, and doravirine has never been compared with INSTIs, the preferred third agent for most patients. (See "Overview of antiretroviral agents used to treat HIV", section on 'Doravirine'.)

CONSIDERATIONS PRIOR TO INITIATING TREATMENT — Most patients should start a regimen that includes an integrase inhibitor with a nucleoside reverse transcriptase inhibitor (NRTI) pair or lamivudine. (See 'Approach for most patients' below.)

To help determine which antiretroviral therapy (ART) regimen is best for a particular patient, clinicians should take into account several patient and laboratory-related factors. (See "Initial evaluation of adults with HIV".)

These include:

●The patient's comorbid conditions and degree of organ dysfunction (eg, heart disease, osteoporosis, renal insufficiency, chronic hepatitis B virus infection, tuberculosis, and/or psychiatric conditions). (See 'Additional considerations' below and "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions".)

●For women of childbearing potential, a pregnancy test should be obtained. In addition, clinicians should assess the patient's desire to become pregnant and/or commitment to using effective contraception. (See 'Persons of childbearing potential/persons who are pregnant' below.)

●The plasma HIV RNA level (ie, viral load) and CD4 cell count. (See 'Use of two-drug regimens in select patients' below and "Overview of antiretroviral agents used to treat HIV", section on 'Abacavir' and "Overview of antiretroviral agents used to treat HIV", section on 'Rilpivirine'.)

●The impact of factors related to the regimen itself (eg, pill burden, pill size, potential for drug interactions, food/fasting requirements). (See "Overview of antiretroviral agents used to treat HIV".)

●Drug availability and cost. (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings", section on 'Recommendations from the World Health Organization'.)

●Baseline drug resistance testing using an HIV genotype assay to detect the presence and/or characteristics of drug-resistant virus, which has been reported to be as high as 16 percent in treatment-naïve patients [1]. This testing should include reverse transcriptase (nucleoside and non-nucleoside reverse transcriptase) and protease inhibitor resistance. Resistance testing for integrase strand transfer inhibitors (INSTIs) is not routinely required unless the source is known to have INSTI treatment failure or resistance. Although transmitted resistance to all major drug classes has been reported, transmission of virus resistant to INSTIs is rare. (See "Overview of HIV drug resistance testing assays".)

Except for pregnancy status, most of this information does not need to be known prior to initiating one of the preferred regimens (table 2), which include tenofovir-emtricitabine with either bictegravir or dolutegravir. Given the general desire to start ART at the first patient visit or shortly thereafter, therapy can be modified if a laboratory test comes back warranting a change in treatment. (See 'Approach for most patients' below and "When to initiate antiretroviral therapy in persons with HIV", section on 'Timing of treatment'.)

However, on rare occasion, a regimen including abacavir may be considered. In this situation, testing for HLA-B*5701 must be obtained before initiating therapy. Abacavir is contraindicated if the patient is positive for the HLA-B*5701 allele, since persons who test positive for HLA-B*5701 are at high risk for developing an abacavir hypersensitivity reaction. (See "Abacavir hypersensitivity reaction".)

REGIMEN SELECTION — For treatment-naïve patients, we typically recommend an antiretroviral therapy (ART) regimen that contains the nucleoside reverse transcriptase inhibitor (NRTI) pair tenofovir plus either emtricitabine or lamivudine, and a third agent from a different class. Multiple comparative clinical trials have found this approach to be effective in suppressing HIV RNA, minimizing drug toxicity, and/or reducing HIV-related morbidity and mortality [29-32]. The use of additional agents does not improve the clinical, immunologic, or virologic outcomes [30,33]. By contrast, in select patients, data support the use of the two-drug regimen dolutegravir-lamivudine [15,34]. (See 'Use of two-drug regimens in select patients' below.)

Approach for most patients

●Preferred regimens – For most patients initiating an antiretroviral regimen, we suggest one of the following integrase strand transfer inhibitor (INSTI)-containing regimens (table 2):

•Bictegravir-emtricitabine-tenofovir alafenamide

•Dolutegravir plus tenofovir alafenamide-emtricitabine

If tenofovir alafenamide (TAF) is not available and the patient is otherwise healthy, dolutegravir plus tenofovir disoproxil fumarate-emtricitabine is a reasonable alternative. Although TAF is associated with less renal toxicity and has less effect on bone density than tenofovir disoproxil fumarate (TDF) [8-12], TDF remains an effective and well-tolerated choice for patients with normal renal function and for those without evidence of bone disease. (See "Overview of antiretroviral agents used to treat HIV", section on 'Tenofovir'.)

These regimens can be started pending the results of the initial evaluation, since they can be used regardless of the viral load or CD4 count, are suitable for patients with chronic hepatitis B (HBV) or adherence concerns, and are most likely to be active in patients with transmitted drug resistance. The benefits of initiating ART soon after diagnosis are presented in a separate topic review. (See "When to initiate antiretroviral therapy in persons with HIV", section on 'Timing of treatment'.)

The single-pill regimen dolutegravir-abacavir-lamivudine is also effective in suppressing the viral load [35]; however, we do not usually choose this regimen for initial therapy since there is a greater body of evidence supporting the safety and tolerability of a tenofovir-containing regimen [3,36-39], and it is only suitable for patients without HBV coinfection who are HLA-B*5701 negative and at low cardiovascular risk. In addition, for most patients who cannot take tenofovir, dolutegravir-lamivudine can be used. (See 'Use of two-drug regimens in select patients' below.)

●Potential contraindications and adverse effects – On rare occasions, the preferred regimens described above may not be appropriate because of the presence of certain concurrent conditions (eg, severely reduced kidney function, severe osteoporosis) or characteristics (eg, persons who are of childbearing potential or are pregnant). There may also be drug interactions that preclude their use or require dose adjustments (eg, rifamycins, certain anticonvulsants). Regimen selection in these populations is discussed elsewhere. (See 'Additional considerations' below and "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions".)

In addition, a potential disadvantage of using dolutegravir plus tenofovir alafenamide-emtricitabine or bictegravir-emtricitabine-tenofovir alafenamide is they appear to have a higher rate of weight gain compared with TDF-containing regimens, especially when tenofovir disoproxil fumarate-emtricitabine is combined with efavirenz [13,17]; however, there are insufficient data to change our recommendations based upon these findings. Specifically, it is not clear if the TDF- and efavirenz-based regimens suppress weight or the TAF- and INSTI-based regimens cause weight gain, or a combination of these factors.

Dolutegravir is also associated with an increased risk of central nervous system side effects (insomnia, headache) compared with other INSTIs. Whether bictegravir has a lower incidence of these side effects compared with dolutegravir is not yet known.

Additional information on the these commonly used agents is presented elsewhere. (See 'Commonly used agents' above and "Overview of antiretroviral agents used to treat HIV", section on 'Integrase strand transfer inhibitors (INSTIs)'.)

●Rationale for preferred regimens – Data supporting the use of an INSTI as part of initial therapy derive from several comparative clinical trials that have demonstrated equivalent and, in some cases, superior efficacy when compared with both boosted protease inhibitors (PIs) and efavirenz [4,6,8,35,40-47]. Two representative studies supporting the superiority of INSTI-containing regimens are:

•The SINGLE study, in which 833 patients without prior treatment were randomized to receive abacavir-lamivudine plus dolutegravir or the single coformulated tablet of tenofovir disoproxil fumarate-emtricitabine-efavirenz [35]. In this trial, dolutegravir was superior to efavirenz at 48 weeks, with more frequent viral suppression to <50 copies/mL (88 versus 81 percent; adjusted treatment difference 7 percent, 95% CI 2-12) and higher CD4 counts (267 versus 208 cells/microL; difference 59 cells, 95% CI 33-84); there was also shorter median time to viral suppression (28 versus 84 days). These outcomes appeared to be driven by the better tolerability of the dolutegravir-containing regimen compared with the efavirenz-containing regimen.

•The FLAMINGO study, in which 484 patients received tenofovir disoproxil fumarate-emtricitabine plus either open-label dolutegravir or ritonavir-boosted darunavir [41]. In this trial, patients in the dolutegravir arm were more likely to have a viral load <50 copies/mL at 48 weeks (90 versus 83 percent of patients; adjusted difference 7.1 percent, 95% CI 0.9-13.2), with the differences being more pronounced in those with low CD4 cell counts or higher viral loads.

In addition to these clinical trials, an observational cohort study of 31,930 individuals evaluating trends in virologic suppression from 1997 to 2015 found that an INSTI-containing regimen was associated with a reduced likelihood of having a detectable viral load compared with other regimens (odds ratio 0.54, 95% CI 0.51-0.57) [48].

Among the available INSTIs, we prefer bictegravir or dolutegravir for several reasons. For one, they have a high barrier to resistance [42,49-53]. As an example, in the only large clinical trial comparing INSTI-containing regimens, dolutegravir had a lower risk for treatment-emergent resistance than raltegravir in patients with virologic failure (4 versus 17 patients; adjusted difference -3.7 percent, 95% CI -6.1 to -1.2) [53], and the resistance profile of bictegravir is similar to dolutegravir. Dolutegravir- and bictegravir-containing regimens also have a lower risk of drug interactions compared with those that contain elvitegravir, since they do not require a pharmacokinetic boosting.

As discussed above, we typically prefer TAF rather than TDF; while they have equivalent efficacy, TAF is associated with less renal toxicity and has less effect on bone density than TDF [8-12]. These findings were best demonstrated in two randomized studies that included 1733 persons with HIV and compared elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide with elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate [8]. In these trials, more than 90 percent of patients achieved a plasma HIV RNA <50 copies/mL after 48 weeks, regardless of which agent they received; however, those who received the TAF-containing regimen had significantly smaller increases in serum creatinine (0.08 versus 0.12 mg/dL), less proteinuria (median percent change -3 versus 20), and smaller decreases in bone mineral density (median percent change spine: -1.30 versus -2.86; hip -0.66 versus -2.95).

Use of two-drug regimens in select patients — Dolutegravir-lamivudine is the only two-drug ART regimen that has been approved for use in treatment-naïve patients. This regimen is most likely to be considered for patients with renal impairment when even TAF should be avoided. (See "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions", section on 'Reduced kidney function'.)

However, in certain situations, the two-drug regimen dolutegravir-lamivudine may be appropriate for otherwise healthy treatment-naïve patients initiating therapy. Although there is less long-term experience with this regimen compared with the preferred regimens above, some patients may want to minimize the number of medications they take in an effort to reduce any potential toxicity.

If dolutegravir-lamivudine is being considered, all of the following conditions must be met:

●The HIV viral load must be less than 500,000 copies/mL.

●There must be no evidence of transmitted resistance to NRTIs or INSTIs (if INSTI resistance testing was obtained as part of the initial evaluation). (See 'Considerations prior to initiating treatment' above.)

●The patient must have no evidence of chronic HBV infection.

●The patient must not be taking any concurrent medications that would significantly reduce the levels of either antiretroviral agent (eg, rifampin lowers dolutegravir levels).

Patients receiving dolutegravir-lamivudine should ideally have a CD4 count >200 cells/microL. A low CD4 count is not a contraindication to using this regimen, but we generally avoid dolutegravir-lamivudine in such patients if there are other good treatment options since few patients with advanced immunosuppression have been treated with dolutegravir-lamivudine. In addition, in the comparative trial described below, those who had a low CD4 count were less likely to achieve a viral load <50 copies at week 48, although the lower results were mostly due to study dropout, not virologic failure.

Dolutegravir-lamivudine was found to have similar efficacy compared with dolutegravir plus tenofovir disoproxil fumarate-emtricitabine at 48 weeks in two large, randomized trials that included 1433 treatment-naïve patients with an HIV-1 RNA ≤500,000 copies/mL [15]. In these trials, virologic suppression (HIV RNA <50 copies/mL) was achieved in 91 and 93 percent of those in the two- or three-drug arm, respectively (adjusted treatment difference -1.7 percent, 95% CI -4.4 to 1.1). Among those with virologic failure, no treatment-related resistance was seen through 48 weeks of follow-up, but one patient in the two-drug arm developed both lamivudine and dolutegravir resistance at week 144 [54]. In a smaller, single-arm study evaluating dolutegravir plus lamivudine in 120 treatment-naïve patients with a median CD4 count of 387 cells/microL and HIV-1 RNA of approximately 40,000 copies/mL, three patients had virologic failure, and the M184V reverse transcriptase and R263R/K integrase mutations developed in one participant [34].

Other two-drug regimens, such as those that use a pharmacologically boosted protease inhibitor (eg, boosted darunavir) with either dolutegravir or lamivudine, have also been studied [55-57]. However, high-quality data are limited, and we generally do not use these alternative two-drug regimens for initial therapy.

Additional considerations — Certain patients will have concurrent conditions or characteristics that impact the choice of regimen. Although many of these patients can use one of the preferred regimens described above, some may benefit from a different regimen that uses an NRTI combination with a different third active drug, such as a PI or a non-nucleoside reverse transcriptase inhibitor (NNRTI) (table 3). The decision to use an alternative regimen is based upon specific patient characteristics (eg, comorbid conditions, adherence concerns, desire to become pregnant), the patient's CD4 count and viral load, and drug-drug interactions. If more than one comorbid condition is present, the clinician should review the options for each relevant scenario and select the most appropriate combination.

Patients with adherence concerns — Patients who are at high risk for taking their regimen intermittently (eg, history of poor adherence) may be at increased risk of developing drug-resistant virus. Thus, we administer a regimen with a high barrier to resistance, such as a nucleos(t)ide combination with either bictegravir, dolutegravir, or a pharmacologically boosted PI as the third agent. (See 'Commonly used agents' above.)

One of the preferred three-drug INSTI-containing regimens should be suitable for patients with adherence concerns. However, if one of these regimens is not available, then darunavir-cobicistat, coformulated with tenofovir alafenamide and emtricitabine, is an appropriate alternative. In general, we do not use the two-drug regimen dolutegravir-lamivudine for patients with adherence concerns given the limited long-term data.

Patients with transmitted drug resistance — Patients with transmitted drug resistance should generally be managed in consultation with a provider who has experience treating individuals with drug-resistant virus. For such patients, the choice of regimen depends upon the specific resistance pattern.

For most patients with transmitted drug resistance, one of the preferred three-drug ART regimens can be used (table 2 and table 3). In the United States, the most common type of transmitted drug resistance is to the NNRTI class [58]. In addition, when NRTI resistance is transmitted, dolutegravir plus tenofovir-emtricitabine or bictegravir-emtricitabine-tenofovir alafenamide has been found to be effective, as long as there is at least one fully active NRTI in the regimen [59-62]. However, on the rare occasion when a patient has high-level transmitted NRTI resistance (eg, K65R), we generally use boosted darunavir plus dolutegravir. There is no role for the other two-drug regimens (eg, dolutegravir or boosted darunavir in combination with lamivudine) in this setting. (See 'Use of two-drug regimens in select patients' above.)

Baseline INSTI resistance is extremely uncommon, and routine testing for baseline INSTI resistance is not recommended unless the source is known to have INSTI treatment failure or resistance [1,63]. More detailed information on regimen selection in the setting of INSTI resistance is found elsewhere. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy", section on 'Patients with drug-resistant virus'.)

Regimens for patients with comorbid conditions — Regimen selection can be impacted by the presence of certain comorbid conditions, such as reduced kidney function, osteoporosis, chronic HBV infection, tuberculosis, and heart disease. Considerations for regimen selection in these patient groups are discussed in a separate topic review. (See "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions".)

Resource-limited settings — Regimen selection in resource-limited settings is discussed elsewhere. (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings".)

Persons of childbearing potential/persons who are pregnant — Similar to others, those who are planning to conceive or are pregnant should generally be started on a regimen that consists of a dual NRTI combination plus an integrase inhibitor. Preferred antiretroviral agents are those for which there are substantial experience and data documenting virologic efficacy, maternal and fetal safety, and tolerability during pregnancy. Detailed discussions of regimen selection and the safety of antiretroviral medications in these populations are found elsewhere. (See "HIV and women", section on 'Individuals of childbearing potential' and "Safety and dosing of antiretroviral medications in pregnancy", section on 'Integrase inhibitors' and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings", section on 'ART selection and management' and "Prevention of vertical HIV transmission in resource-limited settings", section on 'Regimen management'.)

ANTIRETROVIRAL AGENTS AND COMBINATIONS TO AVOID — Certain antiretroviral agents or combinations of antiretroviral medications should not be used because of toxicity, lack of efficacy, or drug antagonism. A more detailed discussion of the individual agents is found elsewhere. (See "Overview of antiretroviral agents used to treat HIV".)

●Nucleoside reverse transcriptase inhibitors (NRTIs)

•Tenofovir and abacavir do not provide additive or synergistic activity when used together, and may increase the risk of resistance to both drugs with virologic failure [64].

•Lamivudine and emtricitabine should not be used together since these individual agents are similar with the same primary resistance mutation (ie, M184V). (See "Interpretation of HIV drug resistance testing".)

•Regimens that include three NRTIs are not as effective as regimens that combine drugs from different classes and are no longer recommended [64-66].

●Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

•The combination of efavirenz and nevirapine together produces more side effects and is less efficacious than standard regimens with either drug alone [67].

•Etravirine has not been studied in large randomized clinical trials in treatment-naïve patients and is thus not recommended for such patients [1].

●Protease inhibitors (PIs)

•Dual PI combinations are not recommended for initial HIV therapy since they are often associated with significant lipid abnormalities.

•Atazanavir should be administered with a pharmacologic boosting agent, especially if given with tenofovir.

●CCR5 inhibitors — In general, initial regimens containing the CCR5 inhibitor maraviroc have not been as effective as comparators [68,69]. As a result, we do not use maraviroc as initial therapy for treatment-naïve patients.

PROVIDER EXPERTISE — The management of antiretroviral therapy (ART) can be complex and should be delivered by or in consultation with providers with specific training. Multiple studies have shown that provider experience correlates with better patient outcomes [70-74]. The HIV Medicine Association of the Infectious Diseases Society of America defines an "HIV provider" as a physician with board certification or equivalent in one of the medical specialties/subspecialties recognized by the American Board of Medical Specialties or the American Osteopathic Association; the physician should have cared for at least 25 active patients with HIV infection during the preceding 36 months and should have had at least 40 hours of continuing medical education on HIV-specific subject matter during the same time period [75]. Significant clinical experience in HIV medicine over at least five years should be considered in the absence of board certification.

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: Starting treatment for HIV (The Basics)" and "Patient education: HIV/AIDS (The Basics)")

●Beyond the Basics topics (see "Patient education: Initial treatment of HIV (Beyond the Basics)" and "Patient education: Tips for taking HIV medications by mouth (Beyond the Basics)" and "Patient education: Testing for HIV (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●The optimal goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality (from both infectious and noninfectious causes) and to prevent the transmission of HIV to others. To achieve and sustain these goals, ART should result in maximal suppression of HIV RNA. (See 'Goals of therapy' above.)

●ART should be offered to all patients with HIV regardless of their immune status (ie, CD4 count). (See 'When to initiate antiretroviral therapy' above.)

●There are more than 30 antiretroviral medications from 5 major classes currently available for the management of patients with HIV (table 1). The most commonly used antiretroviral agents for treatment-naïve patients include nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). (See 'Antiretroviral agents' above.)

●To optimize individual regimens, we evaluate the treatment-naïve patient for the presence or absence of concurrent conditions (eg, renal insufficiency, osteoporosis, chronic hepatitis B virus [HBV] infection, tuberculosis, heart disease) or characteristics (eg, persons who are of childbearing potential or are pregnant). If abacavir is being considered, patients should be tested for the HLA-B*5701 allele. Abacavir is contraindicated if the patient is positive for the HLA-B*5701 allele since such persons are at high risk for developing an abacavir hypersensitivity reaction. (See 'Considerations prior to initiating treatment' above.)

●Baseline drug resistance testing should also be performed to detect the presence and/or characteristics of a drug-resistant virus. This testing should include reverse transcriptase (nucleoside and non-nucleoside reverse transcriptase) and PI resistance; resistance testing for INSTIs is not required unless the source patient is known to have INSTI treatment failure or resistance. (See 'Considerations prior to initiating treatment' above.)

●For most treatment-naïve patients, we suggest an INSTI-containing regimen (Grade 2B). INSTIs have equivalent and, in some cases, superior efficacy when compared with both boosted PIs and efavirenz, and they appear to be better tolerated. (See 'Regimen selection' above.)

•In most otherwise healthy patients, we suggest bictegravir-emtricitabine-tenofovir alafenamide or dolutegravir plus tenofovir alafenamide-emtricitabine rather than other INSTI-containing regimens (table 2) (Grade 2B). These regimens have a high barrier to resistance, do not require a boosting agent (which increases the risk of drug interactions), and can be started pending the results of the initial evaluation. However, the ultimate choice of regimen is based upon specific patient characteristics (eg, comorbid conditions, desire for pregnancy) and the risk of drug interactions (table 3). (See 'Approach for most patients' above and 'Additional considerations' above and "Selecting antiretroviral regimens for treatment-naive persons with HIV-1: Patients with comorbid conditions".)

•When dolutegravir is used as the initial INSTI, we suggest tenofovir alafenamide-emtricitabine rather than tenofovir disoproxil fumarate-emtricitabine as the nucleoside combination (Grade 2B). Tenofovir alafenamide-emtricitabine is associated with less kidney and bone toxicity compared with tenofovir disoproxil fumarate-emtricitabine; however, dolutegravir plus tenofovir disoproxil fumarate-emtricitabine is a reasonable alternative for patients with normal renal function and those without evidence of bone disease. (See 'Approach for most patients' above.)

•The single-pill regimen dolutegravir-abacavir-lamivudine is also effective in suppressing viral load, but we do not usually choose this regimen for initial therapy since there is more evidence supporting the safety and tolerability of tenofovir than abacavir as the nucleoside component. In addition, it is only suitable for patients without HBV coinfection who are HLA-B*5701 negative and at low cardiovascular risk. (See 'Approach for most patients' above.)

●The two-drug combination dolutegravir-lamivudine may be reasonable for select patients with comorbid conditions (eg, reduced kidney function) and otherwise healthy persons who want to minimize the risk of any potential medication toxicity. However, compared with the preferred three-drug regimens, there is less long-term experience, and it cannot be used until the results of the initial workup have returned. If dolutegravir-lamivudine is being considered, it can only be used in patients who have an HIV viral load <500,000 copies/mL, no evidence of chronic HBV infection, and no transmitted NRTI or INSTI resistance. In addition, patients must not be taking concurrent medications that would significantly reduce the levels of either antiretroviral agent. (See 'Use of two-drug regimens in select patients' above.)

●Certain antiretroviral agents, or combinations of antiretroviral medications, should not be used because of toxicity, lack of efficacy, or drug antagonism. (See 'Antiretroviral agents and combinations to avoid' above.)

●Special considerations for regimen selection in those who are planning to conceive, are pregnant, and/or are from resource limited settings are discussed in separate topic reviews. (See "HIV and women" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Prevention of vertical HIV transmission in resource-limited settings" and "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings".)

ACKNOWLEDGMENT — We are saddened by the death of John G Bartlett, MD, who passed away in January 2021. UpToDate gratefully acknowledges Dr. Bartlett's role as author on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Infectious Diseases, and his dedicated and longstanding involvement with the UpToDate program.

  1. United States Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0 (Accessed on December 18, 2019).
  2. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. doi:10.1001/jama.2020.17025 (Accessed on October 15, 2020).
  3. Sax PE, Tierney C, Collier AC, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 2009; 361:2230.
  4. DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012; 379:2429.
  5. Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013; 381:735.
  6. Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med 2014; 161:461.
  7. Molina JM, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet 2011; 378:238.
  8. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015; 385:2606.
  9. Mills A, Crofoot G Jr, McDonald C, et al. Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. J Acquir Immune Defic Syndr 2015; 69:439.
  10. Pozniak A, Arribas JR, Gathe J, et al. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr 2016; 71:530.
  11. Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV 2016; 3:e158.
  12. Wohl D, Oka S, Clumeck N, et al. Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. J Acquir Immune Defic Syndr 2016; 72:58.
  13. Sax PE, Erlandson KM, Lake JE, et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis 2020; 71:1379.
  14. Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV 2020; 7:e666.
  15. Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet 2019; 393:143.
  16. Norwood J, Turner M, Bofill C, et al. Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens. J Acquir Immune Defic Syndr 2017; 76:527.
  17. Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med 2019; 381:803.
  18. NAMSAL ANRS 12313 Study Group, Kouanfack C, Mpoudi-Etame M, et al. Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1. N Engl J Med 2019; 381:816.
  19. Istentress prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022145s036,203045s013,205786s004lbl.pdf (Accessed on February 09, 2023).
  20. Fettiplace A, Stainsby C, Winston A, et al. Psychiatric Symptoms in Patients Receiving Dolutegravir. J Acquir Immune Defic Syndr 2017; 74:423.
  21. Hoffmann C, Welz T, Sabranski M, et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med 2017; 18:56.
  22. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet 2017; 390:2073.
  23. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet 2017; 390:2063.
  24. Stellbrink HJ, Arribas JR, Stephens JL, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV 2019; 6:e364.
  25. Wohl DA, Yazdanpanah Y, Baumgarten A, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV 2019; 6:e355.
  26. Doravirine package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210806s000lbl.pdf.
  27. Orkin C, Squires KE, Molina JM, et al. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis 2019; 68:535.
  28. Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV 2018; 5:e211.
  29. Shafer RW, Smeaton LM, Robbins GK, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003; 349:2304.
  30. Gulick RM, Ribaudo HJ, Shikuma CM, et al. Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA 2006; 296:769.
  31. INITIO Trial International Co-ordinating Committee, Yeni P, Cooper DA, et al. Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial. Lancet 2006; 368:287.
  32. MacArthur RD, Novak RM, Peng G, et al. A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial. Lancet 2006; 368:2125.
  33. Lévy Y, Lelièvre JD, Assoumou L, et al. Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial. Ann Intern Med 2020; 172:297.
  34. Taiwo BO, Zheng L, Stefanescu A, et al. ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL. Clin Infect Dis 2018; 66:1689.
  35. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 2013; 369:1807.
  36. Smith KY, Patel P, Fine D, et al. Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS 2009; 23:1547.
  37. Bansi L, Sabin C, Gilson R, et al. Virological response to initial antiretroviral regimens containing abacavir or tenofovir. J Infect Dis 2009; 200:710.
  38. Sax PE, Tierney C, Collier AC, et al. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis 2011; 204:1191.
  39. Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr 2010; 55:49.
  40. Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013; 27:1771.
  41. Clotet B, Feinberg J, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet 2014; 383:2222.
  42. Eron JJ Jr, Rockstroh JK, Reynes J, et al. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis 2011; 11:907.
  43. Rockstroh JK, DeJesus E, Henry K, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr 2013; 62:483.
  44. Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012; 379:2439.
  45. Zolopa A, Sax PE, DeJesus E, et al. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr 2013; 63:96.
  46. Orrell C, Hagins DP, Belonosova E, et al. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV 2017; 4:e536.
  47. Squires K, Kityo C, Hodder S, et al. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV 2016; 3:e410.
  48. Nance RM, Delaney JAC, Simoni JM, et al. HIV Viral Suppression Trends Over Time Among HIV-Infected Patients Receiving Care in the United States, 1997 to 2015: A Cohort Study. Ann Intern Med 2018; 169:376.
  49. Oliveira M, Mesplède T, Quashie PK, et al. Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS 2014; 28:813.
  50. Osterholzer DA, Goldman M. Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection. Clin Infect Dis 2014; 59:265.
  51. Blanco JL, Varghese V, Rhee SY, et al. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis 2011; 203:1204.
  52. Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2013; 13:927.
  53. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 2013; 382:700.
  54. Cahn P, Sierra Madero J, Arribas JR, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naive adults with HIV-1 infection - 3-year results from the GEMINI studies. Abstract and oral presentation, HIV Glasgow 2020, Glasgow, United Kingdom, October 2020.
  55. Raffi F, Babiker AG, Richert L, et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet 2014; 384:1942.
  56. Cahn P, Andrade-Villanueva J, Arribas JR, et al. Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. Lancet Infect Dis 2014; 14:572.
  57. Figueroa MI, Sued OG, Gun AM, et al. DRV/R/3TC FDC for HIV-1 treatment naive patients: Week 48 results of the ANDES Study. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2018, Boston, MA [Abstract 489].
  58. Porter SE, Campbell E, Westheimer E, et al. Correlates of drug resistance mutations in ART-naive individuals with HIV infection. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle, WA [Abstract 477].
  59. Aboud M et al. Superior efficacy of dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) compared with lopinavir/ritonavir (LPV/RTV) plus 2 NRTIs in second-line treatment: interim data from the DAWNING study. Presented at IAS 2017. 23–26 July 2017. Paris. Oral abstract TUAB0105LB.
  60. Acosta RK, Willkom M, Martin R, et al. Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks. Antimicrob Agents Chemother 2019; 63.
  61. Clutter DS, Fessel WJ, Rhee SY, et al. Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance. J Acquir Immune Defic Syndr 2016; 72:171.
  62. Borghetti A, Ciccullo A, Lombardi F, et al. Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors. HIV Med 2021; 22:22.
  63. Koullias Y, Sax PE, Fields NF, et al. Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus? Clin Infect Dis 2017; 65:1274.
  64. Gallant JE, Rodriguez AE, Weinberg WG, et al. Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects. J Infect Dis 2005; 192:1921.
  65. Gulick RM, Ribaudo HJ, Shikuma CM, et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med 2004; 350:1850.
  66. Landman R, Descamps D, Peytavin G, et al. Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. HIV Clin Trials 2005; 6:291.
  67. van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 2004; 363:1253.
  68. Stellbrink HJ, Le Fevre E, Carr A, et al. Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment. AIDS 2016; 30:1229.
  69. Cooper DA, Heera J, Goodrich J, et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis 2010; 201:803.
  70. Kitahata MM, Koepsell TD, Deyo RA, et al. Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival. N Engl J Med 1996; 334:701.
  71. Brosgart CL, Mitchell TF, Coleman RL, et al. Clinical experience and choice of drug therapy for human immunodeficiency virus disease. Clin Infect Dis 1999; 28:14.
  72. Cunningham WE, Tisnado DM, Lui HH, et al. The effect of hospital experience on mortality among patients hospitalized with acquired immunodeficiency syndrome in California. Am J Med 1999; 107:137.
  73. Landon BE, Wilson IB, McInnes K, et al. Physician specialization and the quality of care for human immunodeficiency virus infection. Arch Intern Med 2005; 165:1133.
  74. Rackal JM, Tynan AM, Handford CD, et al. Provider training and experience for people living with HIV/AIDS. Cochrane Database Syst Rev 2011; :CD003938.
  75. http://www.hivma.org/uploadedFiles/HIVMA/Guidelines_Patient_Care/HIVMA_Standards_Practice_Guidelines/HIV_Guidelines/Guidelines_Content/Revised%20Qualified%20HIV%20Provider%20Policy%20Statement%20Approved%203%2016%2013.pdf (Accessed on December 17, 2013).
Topic 3773 Version 73.0

References

1 : United States Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0 (Accessed on December 18, 2019).

2 : Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. doi:10.1001/jama.2020.17025 (Accessed on October 15, 2020).

3 : Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy.

4 : Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial.

5 : Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study.

6 : Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial.

7 : Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial.

8 : Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials.

9 : Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study.

10 : Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study.

11 : Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial.

12 : Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results.

13 : Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials.

14 : Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial.

15 : Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials.

16 : Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens.

17 : Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV.

18 : Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1.

19 : Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1.

20 : Psychiatric Symptoms in Patients Receiving Dolutegravir.

21 : Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients.

22 : Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial.

23 : Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial.

24 : Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial.

25 : Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial.

26 : Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial.

27 : Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.

28 : Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial.

29 : Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection.

30 : Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial.

31 : Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial.

32 : A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial.

33 : Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.

34 : ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA<500000 Copies/mL.

35 : Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

36 : Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment.

37 : Virological response to initial antiretroviral regimens containing abacavir or tenofovir.

38 : Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results.

39 : Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study.

40 : Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study.

41 : Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study.

42 : Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.

43 : A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results.

44 : Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks.

45 : A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results.

46 : Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study.

47 : Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study.

48 : HIV Viral Suppression Trends Over Time Among HIV-Infected Patients Receiving Care in the United States, 1997 to 2015: A Cohort Study.

49 : Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors.

50 : Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection.

51 : HIV-1 integrase inhibitor resistance and its clinical implications.

52 : Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial.

53 : Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.

54 : Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.

55 : Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial.

56 : Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

57 : Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

58 : Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

59 : Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

60 : Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks.

61 : Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance.

62 : Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors.

63 : Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus?

64 : Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects.

65 : Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection.

66 : Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.

67 : Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

68 : Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment.

69 : Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.

70 : Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival.

71 : Clinical experience and choice of drug therapy for human immunodeficiency virus disease.

72 : The effect of hospital experience on mortality among patients hospitalized with acquired immunodeficiency syndrome in California.

73 : Physician specialization and the quality of care for human immunodeficiency virus infection.

74 : Provider training and experience for people living with HIV/AIDS.

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟