What to Start
Table 7. Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical Scenarios
This table guides clinicians in choosing an initial antiretroviral (ARV) regimen according to various patient and regimen characteristics and specific clinical scenarios. ARV drugs/regimens that are listed in Table 6a as Recommended Initial Regimens for Most People With HIV and in Table 6b as Other Initial Antiretroviral Regimens for Certain Clinical Scenarios are included in this table (see Initial Combination Antiretroviral Regimens for People With HIV). When more than one scenario applies to a person with HIV, clinicians should review considerations for each relevant scenario and use their clinical judgment to select the most appropriate regimen. Please see Table 9 for additional information regarding the advantages and disadvantages of particular ARV medications recommended to be used as initiation therapy.
| Patient or Regimen Characteristics | Clinical Scenario | Consideration(s) | Rationale/Comments |
|---|---|---|---|
| Pre-ART Characteristics | CD4 count <200 cells/mm3 | Do not use RPV-based regimens. | Higher rates of virologic failure have been observed in those with low pre-treatment CD4 counts. |
| HIV RNA >100,000 copies/mL (also see next row if HIV RNA >500,000 copies/mL) | Do not use RPV-based regimens. | Higher rates of virologic failure have been observed in those with high pre-treatment HIV RNA levels. | |
| HIV RNA >500,000 copies/mL | Do Not Use the Following Regimens:
| For DTG/3TC, limited data are available in patients with viral loads above this threshold. | |
| HLA-B*5701 positive or result unknown | Do not use ABC-containing regimens. | ABC hypersensitivity is a potentially fatal reaction that is highly associated with the HLA B*5701 allele. | |
| Prior exposure to oral TDF/(3TC or FTC) or TAF/3TC PrEP | Use DTG or BIC plus two NRTIs. DTG/3TC could be considered if testing confirms no 3TC resistance mutations. | DTG/3TC should be avoided if resistance testing results are not available, as presence of 3TC resistance mutations may lead to use of DTG monotherapy. | |
| Prior exposure to CAB-LA for PrEP | INSTI genotype resistance testing should be performed. If INSTI Resistance Is Present or If ART Needs to Be Started Before Genotype Test Results
If No INSTI Resistance Is Identified
| Mutations conferring resistance to INSTIs have been seen in association with CAB-LA PrEP.
| |
| People with no prior exposure to CAB-LA for PrEP and ARV regimen should be started rapidly and before HIV drug resistance results are available. | Avoid ABC, DTG/3TC, and NNRTI-based regimens. Use
In People Who Used INSTI-Based ART for PEP or Who Are Suspected to Have Acquired HIV From Someone Failing an INSTI-Based Regimen
| Transmitted mutations conferring NNRTI and NRTI resistance are more likely than mutations associated with PI or INSTI resistance.
Because of the current low rates of transmitted INSTI resistance in the United States, even when there is suspicion that HIV was acquired from a partner with virologic failure while on an INSTI, an INSTI-based regimen can be started, pending the results of the INSTI genotype. | |
| ART-Specific Characteristics | A one-pill, once-daily regimen is desired. | STR Options as Initial ART Include the Following:
| Do not use DTG/ABC/3TC if the patient is HLA-B*5701 positive. DTG/3TC is not recommended if HIV RNA is >500,000 copies/mL. Do not use DTG/ABC/3TC or DTG/3TC in the setting of HBV coinfection without another HBV agent. Do not use RPV/TAF/FTC if HIV RNA is >100,000 copies/mL and CD4 count is <200 cells/mm3. |
| Food effects | Regimens That Can Be Taken Without Regard to Food
| Oral bioavailability of these regimens is not significantly affected by food. | |
Regimens That Should Be Taken With Food
| Food improves absorption of these regimens. RPV-containing regimens should be taken with ≥390 calories of food. | ||
| Presence of Other Conditions | Chronic kidney disease (defined as CrCl <60 mL/min) | In general, avoid TDF. For patients with progressively declining renal function, consider avoiding all TFV-containing (TAF or TDF) regimens. Refer to Appendix B, Table 12 for specific ARV drug dosing recommendations in patients with renal impairment. | TDF has been associated with proximal renal tubulopathy. Higher rates of renal dysfunction have been reported in patients using TDF in conjunction with RTV-containing regimens. TAF has less impact on renal dysfunction than TDF. Avoid the use of TDF- or TAF-sparing regimens in the setting of HBV coinfection or unknown HBV status unless also receiving a fully active HBV regimen (see Hepatitis B Virus/HIV Coinfection). |
| Liver disease with cirrhosis | Some ARVs are contraindicated or may require dosage modification in patients with Child-Pugh class B or C disease. | Refer to Appendix B, Table 12 for specific dosing recommendations. Patients with cirrhosis should be carefully evaluated by an expert in advanced liver disease. | |
| Concern for weight gain | For many people with HIV, gaining weight after starting ART is part of a “return to health.” However, some ARV regimens are associated with greater weight increase than others. | Reasons for differences in weight gain among ART regimens are unknown. Note: Weight gain should not be a reason to avoid taking an INSTI-based regimen. | |
| Osteoporosis | Avoid TDF.a | TDF is associated with decreases in BMD, along with renal tubulopathy, urine phosphate wasting, and resultant osteomalacia. TAFa and ABC are associated with smaller declines in BMD than TDF. | |
| Psychiatric illnesses | Consider avoiding RPV-based regimens. Patients on INSTI-based regimens who have preexisting psychiatric conditions should be closely monitored. Some ARVs are contraindicated, and some psychiatric medications need dose adjustments when coadministered with certain ARVs. | RPV can exacerbate psychiatric symptoms and may be associated with suicidality. Some INSTIs have been associated with adverse neuropsychiatric effects in some retrospective cohort studies and case series. See the drug–drug interaction tables (Tables 24a, 24b, 24d, and 24g) for dosing recommendations when drugs used for psychiatric illnesses are used with certain ARVs. | |
| Cardiac QTc interval prolongation | Consider avoiding RPV-based regimens if the patient is taking other medications with known risk of Torsades de Pointes or in patients at higher risk of Torsades de Pointes. | High RPV concentrations may cause QTc prolongation. | |
| High risk for CV events | Consider avoiding ABC-based regimens. Refer to Hyperlipidemia, below, for regimens associated with more favorable lipid profiles. | An increased risk of CV events with ABC has been observed in some, but not all, studies. Certain ARV regimens are associated with more favorable lipid profiles than other regimens. | |
| Hyperlipidemia | PI/c and PI/r have been associated with hyperlipidemia. BIC, DOR, DTG, and RPV have fewer lipid effects. | TDF has been associated with lower lipid levels than ABC or TAF. | |
| Patients with history of poor adherence to non-ARV medications or inconsistent engagement in care | Consider using regimens with a boosted PI or BIC or DTG. | These regimens have a high genetic barrier to resistance. | |
| Pregnancy | Refer to the Perinatal Guidelines for further guidance on ARV use during pregnancy. | ||
| Presence of Coinfections | HBV infection | Avoid regimens that do not contain NRTIs. Use (TDF or TAF) with (FTC or 3TC) as part of the ARV regimen. If TDF and TAF Are Contraindicated
| TDF, TAF, FTC, and 3TC are active against both HIV and HBV. 3TC- or FTC-associated HBV resistance mutations can emerge when these drugs are used without another drug that is active against HBV. |
| HCV treatment required | Refer to recommendations in Hepatitis C Virus/HIV Coinfection, with special attention to potential interactions between ARV drugs and HCV drugs. | ||
| Concomitant use with rifamycin antibiotics (e.g., rifabutin, rifampin, and rifapentine) | Recommended regimens may require dose adjustment. See the drug–drug interaction tables (Tables 24a, 24b, 24c, 24d, 24e, 24f, 24g, 25a, and 25b) and Tuberculosis/HIV Coinfection for information on ARV use with rifamycin antibiotics. | Rifamycin antibiotics are inducers of CYP3A4 and UGT1A1 enzymes, causing significant decreases in concentrations of PIs, INSTIs, and RPV. | |
a TAF and TDF are two U.S. Food and Drug Administration–approved forms of TFV. TAF has fewer bone and kidney toxicities than TDF, whereas TDF is associated with lower lipid levels. Safety, cost, and access are among the factors to consider when choosing between these drugs. Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; BMD = bone mineral density; CABLA = long-acting cabotegravir; CD4 = CD4 T lymphocyte; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; FTC = emtricitabine; HBV = hepatitis B virus; HCV = hepatitis C virus; HLA = human leukocyte antigen; INSTI = integrase strand transfer inhibitor; NNRTI = non nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = cobicistat-boosted protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; PEP = post-exposure prophylaxis; PrEP = preexposure prophylaxis; QTc = QT corrected for heart rate; RPV = rilpivirine; RTV = ritonavir; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; UGT = uridine diphosphate glucuronosyltransferase | |||
What to Start
Table 7. Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical Scenarios
| Patient or Regimen Characteristics | Clinical Scenario | Consideration(s) | Rationale/Comments |
|---|---|---|---|
| Pre-ART Characteristics | CD4 count <200 cells/mm3 | Do not use RPV-based regimens. | Higher rates of virologic failure have been observed in those with low pre-treatment CD4 counts. |
| HIV RNA >100,000 copies/mL (also see next row if HIV RNA >500,000 copies/mL) | Do not use RPV-based regimens. | Higher rates of virologic failure have been observed in those with high pre-treatment HIV RNA levels. | |
| HIV RNA >500,000 copies/mL | Do Not Use the Following Regimens:
| For DTG/3TC, limited data are available in patients with viral loads above this threshold. | |
| HLA-B*5701 positive or result unknown | Do not use ABC-containing regimens. | ABC hypersensitivity is a potentially fatal reaction that is highly associated with the HLA B*5701 allele. | |
| Prior exposure to oral TDF/(3TC or FTC) or TAF/3TC PrEP | Use DTG or BIC plus two NRTIs. DTG/3TC could be considered if testing confirms no 3TC resistance mutations. | DTG/3TC should be avoided if resistance testing results are not available, as presence of 3TC resistance mutations may lead to use of DTG monotherapy. | |
| Prior exposure to CAB-LA for PrEP | INSTI genotype resistance testing should be performed. If INSTI Resistance Is Present or If ART Needs to Be Started Before Genotype Test Results
If No INSTI Resistance Is Identified
| Mutations conferring resistance to INSTIs have been seen in association with CAB-LA PrEP.
| |
| People with no prior exposure to CAB-LA for PrEP and ARV regimen should be started rapidly and before HIV drug resistance results are available. | Avoid ABC, DTG/3TC, and NNRTI-based regimens. Use
In People Who Used INSTI-Based ART for PEP or Who Are Suspected to Have Acquired HIV From Someone Failing an INSTI-Based Regimen
| Transmitted mutations conferring NNRTI and NRTI resistance are more likely than mutations associated with PI or INSTI resistance.
Because of the current low rates of transmitted INSTI resistance in the United States, even when there is suspicion that HIV was acquired from a partner with virologic failure while on an INSTI, an INSTI-based regimen can be started, pending the results of the INSTI genotype. | |
| ART-Specific Characteristics | A one-pill, once-daily regimen is desired. | STR Options as Initial ART Include the Following:
| Do not use DTG/ABC/3TC if the patient is HLA-B*5701 positive. DTG/3TC is not recommended if HIV RNA is >500,000 copies/mL. Do not use DTG/ABC/3TC or DTG/3TC in the setting of HBV coinfection without another HBV agent. Do not use RPV/TAF/FTC if HIV RNA is >100,000 copies/mL and CD4 count is <200 cells/mm3. |
| Food effects | Regimens That Can Be Taken Without Regard to Food
| Oral bioavailability of these regimens is not significantly affected by food. | |
Regimens That Should Be Taken With Food
| Food improves absorption of these regimens. RPV-containing regimens should be taken with ≥390 calories of food. | ||
| Presence of Other Conditions | Chronic kidney disease (defined as CrCl <60 mL/min) | In general, avoid TDF. For patients with progressively declining renal function, consider avoiding all TFV-containing (TAF or TDF) regimens. Refer to Appendix B, Table 12 for specific ARV drug dosing recommendations in patients with renal impairment. | TDF has been associated with proximal renal tubulopathy. Higher rates of renal dysfunction have been reported in patients using TDF in conjunction with RTV-containing regimens. TAF has less impact on renal dysfunction than TDF. Avoid the use of TDF- or TAF-sparing regimens in the setting of HBV coinfection or unknown HBV status unless also receiving a fully active HBV regimen (see Hepatitis B Virus/HIV Coinfection). |
| Liver disease with cirrhosis | Some ARVs are contraindicated or may require dosage modification in patients with Child-Pugh class B or C disease. | Refer to Appendix B, Table 12 for specific dosing recommendations. Patients with cirrhosis should be carefully evaluated by an expert in advanced liver disease. | |
| Concern for weight gain | For many people with HIV, gaining weight after starting ART is part of a “return to health.” However, some ARV regimens are associated with greater weight increase than others. | Reasons for differences in weight gain among ART regimens are unknown. Note: Weight gain should not be a reason to avoid taking an INSTI-based regimen. | |
| Osteoporosis | Avoid TDF.a | TDF is associated with decreases in BMD, along with renal tubulopathy, urine phosphate wasting, and resultant osteomalacia. TAFa and ABC are associated with smaller declines in BMD than TDF. | |
| Psychiatric illnesses | Consider avoiding RPV-based regimens. Patients on INSTI-based regimens who have preexisting psychiatric conditions should be closely monitored. Some ARVs are contraindicated, and some psychiatric medications need dose adjustments when coadministered with certain ARVs. | RPV can exacerbate psychiatric symptoms and may be associated with suicidality. Some INSTIs have been associated with adverse neuropsychiatric effects in some retrospective cohort studies and case series. See the drug–drug interaction tables (Tables 24a, 24b, 24d, and 24g) for dosing recommendations when drugs used for psychiatric illnesses are used with certain ARVs. | |
| Cardiac QTc interval prolongation | Consider avoiding RPV-based regimens if the patient is taking other medications with known risk of Torsades de Pointes or in patients at higher risk of Torsades de Pointes. | High RPV concentrations may cause QTc prolongation. | |
| High risk for CV events | Consider avoiding ABC-based regimens. Refer to Hyperlipidemia, below, for regimens associated with more favorable lipid profiles. | An increased risk of CV events with ABC has been observed in some, but not all, studies. Certain ARV regimens are associated with more favorable lipid profiles than other regimens. | |
| Hyperlipidemia | PI/c and PI/r have been associated with hyperlipidemia. BIC, DOR, DTG, and RPV have fewer lipid effects. | TDF has been associated with lower lipid levels than ABC or TAF. | |
| Patients with history of poor adherence to non-ARV medications or inconsistent engagement in care | Consider using regimens with a boosted PI or BIC or DTG. | These regimens have a high genetic barrier to resistance. | |
| Pregnancy | Refer to the Perinatal Guidelines for further guidance on ARV use during pregnancy. | ||
| Presence of Coinfections | HBV infection | Avoid regimens that do not contain NRTIs. Use (TDF or TAF) with (FTC or 3TC) as part of the ARV regimen. If TDF and TAF Are Contraindicated
| TDF, TAF, FTC, and 3TC are active against both HIV and HBV. 3TC- or FTC-associated HBV resistance mutations can emerge when these drugs are used without another drug that is active against HBV. |
| HCV treatment required | Refer to recommendations in Hepatitis C Virus/HIV Coinfection, with special attention to potential interactions between ARV drugs and HCV drugs. | ||
| Concomitant use with rifamycin antibiotics (e.g., rifabutin, rifampin, and rifapentine) | Recommended regimens may require dose adjustment. See the drug–drug interaction tables (Tables 24a, 24b, 24c, 24d, 24e, 24f, 24g, 25a, and 25b) and Tuberculosis/HIV Coinfection for information on ARV use with rifamycin antibiotics. | Rifamycin antibiotics are inducers of CYP3A4 and UGT1A1 enzymes, causing significant decreases in concentrations of PIs, INSTIs, and RPV. | |
a TAF and TDF are two U.S. Food and Drug Administration–approved forms of TFV. TAF has fewer bone and kidney toxicities than TDF, whereas TDF is associated with lower lipid levels. Safety, cost, and access are among the factors to consider when choosing between these drugs. Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; BMD = bone mineral density; CABLA = long-acting cabotegravir; CD4 = CD4 T lymphocyte; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; FTC = emtricitabine; HBV = hepatitis B virus; HCV = hepatitis C virus; HLA = human leukocyte antigen; INSTI = integrase strand transfer inhibitor; NNRTI = non nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = cobicistat-boosted protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; PEP = post-exposure prophylaxis; PrEP = preexposure prophylaxis; QTc = QT corrected for heart rate; RPV = rilpivirine; RTV = ritonavir; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; UGT = uridine diphosphate glucuronosyltransferase | |||
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