Australian Commentary on the US DHHS Guidelines for the use of Antiretroviral Agents in Pediatric HIV infection

US DHHS Guidelines with Australian Commentary

To visit the Adult Antiretroviral Guidelines, visit this link.

ARV Guidelines > Pediatric Guidelines > Management of Children Receiving ART

Management of Children Receiving Antiretroviral Therapy

DHHS Last Updated: April 2023Australian Commentary Last Updated: July 2023

AU Comment: Raltegravir granules

Raltegravir granules are NOT currently available in Australia.

AU Comment: Age and weight based criteria

Age and weight based criteria may differ in Australia.

AU Comment: Maraviroc

Maraviroc is NOT licensed for children in Australia.

AU Comment: ibalizumab

ibalizumab is NOT currently licensed for children in Australia.

AU Comment: Travel with ART

A supportive letter may be required to travel with large volumes of antiretroviral medications by Australian immigration.

In the United States, most children with HIV are receiving antiretroviral therapy (ART), making treatment-experienced children the norm. Providers may consider antiretroviral (ARV) regimen changes for the following reasons:

Treatment simplification: Modifying ARV regimens in children who are currently receiving effective ART to simplify the
Treatment optimization: Increasing the treatment potency or barrier to resistance of an effective but older or potentially fragile regimen or improving the adverse-event
Toxicity management: Recognizing and managing ARV drug toxicity or intolerance (see Management of Medication Toxicity or Intolerance).
Treatment failure: Recognizing and managing treatment failure (see Recognizing and Managing Antiretroviral Treatment Failure).

Modifying Antiretroviral Regimens in Children with Sustained Virologic Suppression on Antiretroviral Therapy

Panel’s Recommendations

Children who have sustained virologic suppression on their current antiretroviral (ARV) regimen should be evaluated regularly for opportunities to change to a new regimen that facilitates adherence, simplifies administration, increases ARV potency or barrier to drug resistance, and decreases the risk of drug-associated toxicity (AII).
Before changing a patient’s ARV regimen, clinicians must carefully consider the patient’s previous regimens, past episodes of ARV therapy failure, prior drug-resistance test results, drug cost, and insurance coverage, as well as the patient’s ability to tolerate the new drug regimen (AIII). Archived drug resistance can limit the antiviral activity of a new drug regimen.
Children should be monitored carefully after a change in treatment. Viral load measurement is recommended 2 to 4 weeks after a change in a child’s ARV regimen (BIII).

Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints;

I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

† Studies that include children or children/adolescents, but not studies limited to postpubertal adolescents

Clinicians choose initial ARV regimens for children with HIV by evaluating the pharmacokinetic, safety, and efficacy data for the drugs that are available in formulations suitable for the child’s age and weight at the start of treatment. New ARV drug options may become available as children grow and learn to swallow pills and as new drugs, drug formulations, and data become available. Even in cases wherein patients have achieved sustained virologic suppression (i.e., suppression for 6–12 months) on their current regimen, clinicians should consider switching patients to new ARV regimens to permit the use of pills instead of liquids, reduce pill burden, allow the use of once-daily medications, reduce the risk of adverse events, minimize drug interactions, and align a child’s regimen with widely used, efficacious adult regimens.¹ These changes often enhance adherence and improve quality of life.²

Treatment Simplification

Many infants and children with HIV initiated treatment with twice-daily dosing (especially prior to the approval of integrase strand transfer inhibitor [INSTI] medications ), and regimens included a variety of drug formulations, depending on which formulations were available for a child’s age and weight. Clinicians should regularly review treatment options as children grow, because it may be possible to simplify dosing using coformulated drugs and/or once-daily regimens (see Table 1 below). Clinicians also should consider a child’s ART history, drug-resistance test results. Small studies have shown that children who achieve virologic suppression using twice-daily dosing for certain ARV drugs (e.g., abacavir [ABC]) maintain virologic suppression when they are switched from twice-daily dosing to once-daily dosing of the same drugs (see the Abacavir and Nevirapine sections and fixed-dose combinations [FDCs] in Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets and Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets: Minimum Body Weights and Consideration for Use in Children and Adolescents). However, these studies reported mixed results when switching the dosing for lopinavir/ritonavir (LPV/r) from twice daily to once daily. Therefore, once-daily dosing of LPV/r is not recommended.^3-6

Long-acting injectable ARV medications may be considered a treatment simplification approach for some virologically suppressed adolescents. The co-packaged, two-drug injectable ARV regimen of cabotegravir and rilpivirine (CAB and RPV; Cabenuva) is approved by the U.S. Food and Drug Administration (FDA) for use in children weighing ≥35 kilograms and ≥12 years of age, with viral suppression (defined as <50 copies/mL), on a stable ARV regimen, without a history of treatment failure, and without known or suspected drug resistance to either drug. Studies in adults—such as the First Long-Acting Injectable Regimen (FLAIR) and Antiretroviral Therapy as Long-Acting Suppression (ATLAS) trials—have demonstrated non-inferiority in those receiving monthly CAB and RPV injections compared to adults who stayed on a daily three-drug oral regimen.^7,8 Similarly, in the ATLAS-2M trial, injections of CAB and RPV every 2 months were found to be non-inferior to monthly injections.⁹ The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Study 2017 is currently evaluating CAB and RPV in children 12 to 18 years of age. either CAB or RPV, showed acceptable pharmacokinetics, lack of new safety concerns,^7,8 and high acceptability from youth and their caregivers. This ongoing study is now assessing the full two-drug injectable regimen. The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) notes that significant questions remain, including whether an oral lead-in is beneficial and acceptable in the adolescent population, if there are additional adverse effects specific to the pediatric population, if a two-drug nucleoside-sparing regimen for children with significant ARV treatment history¹⁰ will be effective, and what potential implementation challenges will emerge. However, given the FDA approval for those as young as 12 years of age, some providers may consider injectable CAB and RPV in adolescents who meet the approved indications and may benefit from a long-acting injectable regimen. See Cabotegravir and Rilpivirine for additional information about these drugs and the dosing and administration of CAB and RPV, and see Management of the Treatment-Experienced Patient: Optimizing Antiretroviral Therapy in the Setting of Viral Suppression in the Adult and Adolescent ARV Guidelines for practical considerations.

Dolutegravir nucleoside reverse transcriptase inhibitors, darunavir/ritonavir, protease inhibitor.

Treatment Optimization

The aims of treatment optimization may include improving the potency of the regimen, improving a child’s growth or other health outcomes through reduced drug side effects and/or better treated HIV, or maximizing palatability. More studies are directly evaluating treatment optimization in children, and early results support the safety and efficacy of regimen switches for those with viral suppression. Older studies have demonstrated sustained viral suppression and improved growth outcomes in young children who have demonstrated good adherence and no baseline resistance and who were switched from LPV/r-based regimens an efavirenz (EFV)-based regimen (NEVEREST 3).^15-17 Replacing LPV/r with EFV may provide some benefits (e.g., once-daily dosing and a different side- effect profile), but most pediatric HIV experts would prefer replacing LPV/r with an equally potent PI (e.g., darunavir [DRV] or atazanavir [ATV]) or an INSTI (e.g., elvitegravir [EVG], raltegravir, DTG, or bictegravir [BIC]), based on studies in adults and emerging evidence of non-inferiority or superiority in children.^18,19 Although not a switch trial, findings from the randomized controlled Once-daily DTG-based ART in Young People vs. Standard Therapy (ODYSSEY) study of more than 700 children aged <18 years in eight countries showed superior virologic and clinical outcomes in children randomized to optimization with DTG-based ART compared with those in the standard of care (PI- or non-nucleoside reverse transcriptase inhibitor [NNRTI]-based regimens), contributing to evidence supporting optimization with DTG- based regimens.²⁰Additionally, several observational studies in sub-Saharan Africa that are evaluating efforts to optimize pediatric ARV regimens have shown improved viral suppression rates in children that were switched to DTG-based regimens.^22-25 Similarly, a retrospective study from six African countries reporting on 2,655 children aged 0 to ≤19 years demonstrated sustained high levels of viral suppression in children optimized from NNRTI- and PI- based regimens to DTG-based regimens.²⁶ The INSTI-based FDC regimen BIC/emtricitabine (FTC)/ tenofovir alafenamide (TAF)^27,28 EVG/cobicistat/FTC/TAF has shown efficacy in adolescents. Early results from small, randomized studies also show potential for switches to newer-generation NNRTI medications—such as rilpivirine (RPV)²⁹ and doravirine (DOR) in children and adolescents weighing ≥35 kg who have been virologically suppressed on a stable ARV regimen.

Toxicity Management

Several studies of small cohorts of children have demonstrated sustained virologic suppression and reassuring safety outcomes when drugs that have greater long-term toxicity risks are replaced with drugs that are thought to have lower toxicity risks (e.g., replacing stavudine with tenofovir disoproxil fumarate, TAF, zidovudine, or ABC; replacing PIs with NNRTIs), including improved lipid profiles.^31-35 Similarly, adolescents who were switched from EFV to RPV, a newer generation of NNRTIs, showed similar rates of viral suppression with improved metabolic profiles and cognitive outcomes.²⁹ Additionally, studies in adults have shown improved tolerability, lipid profiles, and insulin sensitivity in patients who were switched from PIs to INSTIs,^36-40 and adults who were switched from EFV to an INSTI have shown improvement in neuropsychiatric symptoms. However, the use of INSTIs, as well as TAF, has been associated with weight gain in adults and adolescents, with emerging data showing an association in children.^41-45tenofovir disoproxil fumarate (<1%).

Treatment Failure

Treatment failure is another common reason providers change ARV regimens in children with HIV. This topic is covered in Recognizing and Managing Antiretroviral Treatment Failure.

Regimens That Are Not Recommended for Use in Children

Monotherapy PI regimens (DRV/r, LPV/r, ATV/r)^47,48 and monotherapy regimens of DTG^49,50 have been used to simplify or reduce the toxicity of regimens in adult patients who have sustained virologic suppression, but with varying success. These strategies are still being explored, but they are not currently recommended as management strategies in children because of the lack of data.^48,51-54

Potential Antiretroviral Drug Switches in Children With Virologic Suppression

Table 18 below contains examples of potential ARV drug changes in children with sustained virologic suppression on their current regimen for the purpose of treatment simplification, optimization, or reduced toxicity. When considering such a change, a clinician should first ensure that a recent viral load test indicates that the child is not experiencing virologic failure and that the child has a reliable history of good adherence (assessed by self and parental report, pharmacy refill, prior viral loads, etc.). Among treatment-naive youth in the United States aged 13 to 24 years, some evidence exists that single-tablet regimens (STRs) improve the odds of viral suppression⁵⁵; emerging evidence also supports the safety, efficacy, and tolerability of STRs in younger children.^56-58 Although these data have not been replicated in treatment-experienced adolescents, clinicians should consider using STRs in children and youth with sustained viral suppression because these regimens reduce pill burden and dosing frequency. Clinicians also must consider ART history, tolerability, ability to swallow tablets, and all prior drug-resistance test results to avoid choosing new ARV drugs for which archived drug resistance would reemerge and limit the activity of the regimen.^59-63 The evidence that supports many of these ARV changes is indirect, that is, extrapolated from data about drug performance during initial therapy or follow-up therapy after treatment failure. When such changes are made, careful monitoring (e.g., taking a viral load measurement 2–4 weeks after making the switch to the new regimen) is important to ensure that virologic suppression is maintained.

Table 1. Examples of Changes in Antiretroviral Regimen Components for Children With Sustained Virologic Suppression

This list is not exhaustive and does not necessarily contain all potential treatment options. Instead, it provides examples of changes that could be made. The table includes information only about switching between ARV drugs; it does not include all the information that clinicians should consider before prescribing these drugs, such as drug cost and the patient’s insurance coverage. Refer to the individual drug sections, Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets or as a Co-Packaged Formulation, by Drug Class, and Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents in Appendix A: Pediatric Antiretroviral Drug Information for further information about the use and administration of specific ARV drugs and FDC formulations.

Current ARV Drug(s)	Age, Weight, and Sexual Maturity Rating Requirements	Potential ARV Drug Switch^a	Comment
NRTIs
ABC Twice Daily	Aged ≥3 months^b	ABC once daily	See the Abacavir^b section.
3TC Twice Daily	Aged ≥3 years	3TC once daily	See the Lamivudine section.
3TC Twice Daily	Any age (starting at full-term birth) Any weight	FTC once daily	See the Emtricitabine section.
ZDV	Aged ≥1 months^b	ABC	Less long-term mitochondrial toxicity Children aged ≥3 months can take ABC once daily.
	Weighing 17 kg to <25 kg	TDF	TDF is a reasonable, once-daily option for HLA-B*5701- positive children for whom ABC is not recommended and in whom ZDV is not tolerated. TDF is available as an oral powder and as low-strength tablets alone or in combination with FTC.
	Weighing ≥14 kg	TAF^c	Less long-term mitochondrial toxicity. Once-daily dosing. Only available in coformulation with other ARV drugs; can further reduce pill burden. TAF is preferred over TDF because of the lower risk of bone and renal toxicity, but it may be associated with weight gain and lipid abnormalities.
		FTC/TAF^c
NNRTIs
NVP or EFV	Any age (starting at full-term birth) Weighing ≥2 kg	RAL^d	RAL is preferred over NVP in infants from birth to age 4 weeks who weigh ≥2 kg. Both are dosed twice daily in children. Note that DTG and BIC have a higher barrier to resistance than RAL. In a child >1 month of age, DTG is preferred. See DTG below.
	Age ≥4 weeks Weighing ≥3 kg	DTG	DTG is available as a single drug in dispersible and film- coated tablet formulations, or as part of an FDC tablet, all of which can be dosed once daily if no documented resistance or history of failure with INSTI agents exists. DTG plus FTC/TAF (Descovy) in patients weighing at least 14 kg or the weight-appropriate dose of FTC/TDF (Truvada) can be used in children weighing 20 kg to <25 kg. DTG is available as a component of the FDC ABC/DTG/3TC, which is a complete ARV regimen that can be given to children weighing ≥10 to <25 kg in dispersible tablets (Triumeq PD) and to children and adolescents weighing ≥25 kg in a single tablet to be swallowed (Triumeq). Higher barrier to resistance, which makes it a good choice for patients who have poor adherence. May improve lipid levels. See the Dolutegravir section for more information.
	Aged ≥3 months Weighing ≥5 kg	ATV/r	ATV/r has a potentially greater barrier to resistance; however, taking ATV/r may be difficult for some patients, as ATV oral powder must be mixed with food or a beverage before administration, and the palatability of the RTV oral solution is poor.
	Aged ≥3 years Weighing ≥10 kg	DRV/r	DRV/r has a potentially greater barrier to resistance. DRV/r is administered twice daily to patients aged <12 years but may be administered once daily in children aged ≥12 years who do not have any DRV resistance mutations. Note that the palatability of the RTV oral solution is poor when considering administering to children not able to swallow tablets.
	Weighing ≥14 kg	BIC as Biktarvy	Once-daily dosing. BIC is available as a component of the FDC tablet BIC/FTC/TAF (Biktarvy) in two weight-based ≥14 ≥25 kg. This is a complete ARV regimen that can be taken with or without food.
	Weighing ≥25 kg	EVG as Genvoya	EVG is available as a component of the FDC tablet EVG/c/FTC/TAF (Genvoya), which is a complete ARV regimen that must be taken with food.
	Weighing ≥35 kg	DOR	DOR is available in a once-daily FDC tablet DOR/3TC/TDF (Delstrigo). Fewer side effects than reported with EFV. It has continued activity in the setting of some NNRTI mutations.
	Aged ≥12 years Weighing ≥35 kg	CAB and RPV co-packaged regimen as Cabenuva	Long-acting injectable, complete ARV regimen requiring two IM injections every 1 to 2 months that together are an alternative to daily oral ARV regimens. Must consider prior history of treatment failure and known or suspected drug resistance to individual drugs. Injection site reactions are common but do not often result in discontinuation of the regimen. See Cabotegravir.
	Aged ≥12 years Weighing ≥35 kg	RPV	Lower incidence of adverse lipid effects. May have fewer sleep disturbances and neuropsychiatric symptoms compared to EFV. RPV has continued activity in the setting of some NNRTI mutations.
PIs
LPV/r Twice Daily	Any age (starting at full-term birth) Weighing ≥2 kg	RAL^d	Better palatability. RAL HD can only be given once daily in those weighing ≥40 kg. Unlike LPV/r, the use of RAL is not restricted to infants with a corrected gestational age of ≥42 weeks and a postnatal age of ≥14 days. RAL granules may be difficult to dose for some caregivers.
	Age ≥4 weeks Weighing ≥3 kg	DTG	Once-daily dosing if no documented resistance or history of failure with INSTI agents exists. May be better tolerated, and it can be given as a dispersible tablet in young children. DTG is available as a component of the FDC ABC/DTG/3TC, which is a complete ARV regimen that can be given to children weighing ≥10 kg to <25 kg in dispersible tablets (Triumeq PD) and to children and adolescents weighing ≥25 kg in a single tablet to be swallowed (Triumeq). DTG plus FTC/TAF (Descovy) in those weighing at least 14 kg or the weight-appropriate dose of FTC/TDF (Truvada) can be used in children weighing 20 kg to <25 kg. May improve lipid levels. See the Dolutegravir section for more information.
	Aged ≥3 years Weighing ≥10 kg	EFV	Once-daily dosing. Better palatability. Lower incidence of adverse lipid effects. Review NNRTI mutations before use. See the Efavirenz section for concerns about EFV dosing for children aged <3 years.
	Aged ≥3 months Weighing ≥5 kg	ATV/r	Once-daily dosing. ATV/r may have a lower incidence of adverse lipid effects; however, taking ATV/r may be difficult for some patients, as ATV oral powder must be mixed with food or a beverage before administration, and the palatability of the RTV oral solution is poor.
	Aged ≥3 years Weighing ≥10 kg	DRV/r	DRV/r may have a lower incidence of adverse lipid effects. DRV/r is administered twice daily to patients aged <12 years, but it may be administered once daily in children aged ≥12 years who do not have DRV resistance mutations. Note that palatability of the RTV oral solution is poor when considering administering to children not able to swallow tablets.
	Weighing ≥14 kg	BIC as Biktarvy	Once-daily dosing. BIC is available as a component of the FDC tablet BIC/FTC/TAF (Biktarvy) is a complete ARV regimen that can be taken with or without food.
	Weighing ≥25 kg	EVG as Genvoya	EVG is available as a component of the FDC tablet EVG/c/FTC/TAF (Genvoya), which is a complete ARV regimen that must be taken with food.
	Weighing ≥35 kg	DOR	DOR is available in a once-daily FDC tablet DOR/3TC/TDF (Delstrigo). Fewer side effects than reported with EFV. It has continued activity in the setting of some NNRTI mutations.
	Aged ≥12 years Weighing ≥35 kg	CAB and RPV co-packaged regimen as Cabenuva	Long-acting injectable, complete ARV regimen requiring two IM injections every 1 to 2 months that together are an alternative to daily oral ARV regimens. Must consider prior history of treatment failure and known or suspected drug resistance to individual drugs. Injection site reactions are common but do not often result in discontinuation of the regimen. See Cabotegravir.
	Aged ≥12 years Weighing ≥35 kg	RPV	May be better tolerated. Lower incidence of adverse lipid effects. It has continued activity in the setting of some NNRTI mutations.
INSTIs
RAL	Age >1 month and weighing <14 kg Weighing >14 kg	DTG DTG or BIC	Once-daily dosing. Higher barrier to resistance. DTG is available as a single drug in a dispersible tablet for infants and children weighing ≥3 kg; in a single-drug film-coated tablet for children weighing ≥14 kg; or as an FDC. All of these can be dosed once daily if no documented resistance or history of failure with INSTI agents exists. DTG plus FTC/TAF (Descovy) in those weighing at least 14 kg or the weight-appropriate dose of FTC/TDF (Truvada) can be used in children weighing 20 kg to <25 kg. DTG is available as a component of the FDC ABC/DTG/3TC, which is a complete ARV regimen that can be given to children weighing ≥10 to <25 kg in dispersible tablets (Triumeq PD) and to children and adolescents weighing ≥25 kg in a single tablet to be swallowed (Triumeq). See the Dolutegravir section for more information. BIC has once-daily dosing and a higher barrier to resistance. BIC is available as a component of the FDC tablet BIC/FTC/TAF (Biktarvy) is a complete ARV regimen that can be taken with or without food.
RAL	Aged ≥12 years Weighing ≥35 kg	CAB and RPV co-packaged regimen as Cabenuva	Long-acting injectable, complete ARV regimen requiring two IM injections every 1 to 2 months that together are an alternative to daily oral ARV regimens. Must consider prior history of treatment failure and known or suspected drug resistance to individual drugs. Injection site reactions are common but do not often result in discontinuation of the regimen. See Cabotegravir.
EVG/c	Weighing ≥14 kg	DTG or BIC	Once-daily dosing. Higher barrier to resistance. DTG is available as a single drug in a dispersible tablet for infants and children weighing ≥3 kg; in a single-drug film-coated tablet for children weighing 14 kg; or as an FDC. All of these can be dosed once daily if no documented resistance or history of failure with INSTI agents exists. DTG plus FTC/TAF (Descovy) in those weighing at least 14 kg or the weight-appropriate dose of FTC/TDF (Truvada) can be used in children weighing 20 kg to <25 kg. DTG is available as a component of the FDC ABC/DTG/3TC), which is a complete ARV regimen that can be given to children weighing ≥10 to <25 kg in dispersible tablets (Triumeq PD) and to children and adolescents weighing ≥25 kg in a single tablet to be swallowed (Triumeq), See the Dolutegravir section for more information. BIC has once-daily dosing and a higher barrier to resistance. BIC is available as a component of the FDC tablet BIC/FTC/TAF (Biktarvy) ≥25 kg is a complete ARV regimen that can be taken with or without food.
EVG/c	Aged ≥12 years Weighing ≥35 kg	CAB and RPV co-packaged regimen as Cabenuva	Long-acting injectable, complete ARV regimen requiring two IM injections every 1 to 2 months that together are an alternative to daily oral ARV regimens. Must consider prior history of treatment failure and known or suspected drug resistance to individual drugs. Injection site reactions are common but do not often result in discontinuation of the regimen. See Cabotegravir.
Other
Any Multi-Pill and/or Twice- Daily Regimen	Weighing ≥14 kg to <25 kg	ABC/DTG/3TC (Triumeq PD)	Once-daily dosing. Dispersible tablets with dosage for use in children based on weight. Aligns a child’s regimen with an efficacious regimen that is used in adults. See the Dolutegravir section for more information.
	Weighing ≥14 kg	FTC/TAF^c (Descovy) plus DTG	Once-daily dosing. This regimen may be more desirable because of smaller pill sizes, but it has a higher pill burden (two pills instead of one). Aligns a child’s regimen with an efficacious regimen that is used in adults. See the Dolutegravir section for more information.
	Weighing ≥14 kg	BIC/FTC/TAF (Biktarvy)	Once-daily dosing. Single pill that can be taken with or without food.
	Weighing ≥25 kg	ABC/DTG/3TC (Triumeq)	Once-daily dosing. Single pill to be swallowed. Aligns a child’s regimen with an efficacious regimen that is used in adults. Large pill size may be a deterrent. See the Dolutegravir section for more information.
	Weighing ≥25 kg	EVG/c/FTC/TAF (Genvoya)	Once-daily dosing. Single pill. Alignment with adult ARV regimens. Must be taken with food.
	Weighing ≥35 kg	DOR/3TC/TDF (Delstrigo)	Once-daily dosing. Single pill. Aligns a child’s regimen with an efficacious regimen that is used in adults. Must be taken with food at a consistent time daily. Renal and bone toxicity of TDF limit its use. Review NNRTI mutations and check for drug–drug interactions before use.
	Weighing ≥35 kg SMR 4 or 5	EVG/c/FTC/TDF (Stribild)	Once-daily dosing. Single pill. Aligns a child’s regimen with an efficacious regimen that is used in adults. Must be taken with food. Renal and bone toxicity of TDF limit its use.
	Aged ≥12 years Weighing ≥35 kg	CAB and RPV co-packaged regimen as Cabenuva	Long-acting injectable, complete ARV regimen requiring two IM injections every 1 to 2 months that together are an alternative to daily oral ARV regimens. Must consider prior history of treatment failure and known or suspected drug resistance to individual drugs. Injection site reactions are common but do not often result in discontinuation of the regimen. See Cabotegravir.
	Aged ≥12 years Weighing ≥35 kg	FTC/RPV/TAF (Odefsey)	Once-daily dosing. Single pill. Aligns a child’s regimen with an efficacious regimen that is used in adults. Must be taken with food at a consistent time daily.
	Aged ≥12 years Weighing ≥35 kg SMR 4 or 5	FTC/RPV/TDF (Complera)	Once-daily dosing. Single pill. Aligns a child’s regimen with an efficacious regimen that is used in adults. Must be taken with food at a consistent time daily. Renal and bone toxicity of TDF limit its use.

^a The possibility of planned and unplanned pregnancy should be considered when selecting an ART regimen for an adolescent. When discussing ART options with adolescents of childbearing potential and their caregivers, it is important to consider the benefits and risks of all ARV drugs and to provide the information and counseling needed to support informed decision-making; refer to the Perinatal Guidelines (see Recommendations for Use of Antiretroviral Drugs During Pregnancy, Table 7. Situation- Specific Recommendations for Use of Antiretroviral Drugs in Pregnant People and Nonpregnant People Who Are Trying to Conceive, and Appendix C: Antiretroviral Counseling Guide for Health Care Providers).

^b For infants and young children who are being treated with liquid formulations of ABC, initiation with once-daily ABC is not generally recommended. In clinically stable patients with undetectable viral loads who have had stable CD4 T lymphocyte cell counts on twice-daily ABC, the dose can be changed from twice daily to once daily. ABC is not approved by the U.S. Food and Drug Administration for use in neonates and infants aged <3 months. Recent data from the IMPAACT P1106 trial and two observational cohorts provide reassuring evidence of the safety of ABC in infants aged <3 months. Based on these data, clinicians may consider the use of ABC in infants aged ≥1 month to <3 months, in consultation with a pediatric HIV specialist (see Abacavir).

^c For children and adolescents weighing ≥14 kg to <35 kg, TAF can be used in combination with an INSTI or an NNRTI, but not a boosted PI. For children and adolescents weighing ≥35 kg, TAF can be used in combination with an INSTI, an NNRTI, or a boosted PI.

^d RAL is recommended for twice-daily use in children. Chewable tablets can be used as dispersible tablets starting at 4 weeks of age. RAL HD once daily is only recommended for virologically suppressed children weighing ≥40 kg.

Key: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; ATV/r = atazanavir/ritonavir; BIC = bictegravir; DOR = doravirine; DRV = darunavir; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FDC = fixed-dose combination; FTC = emtricitabine; HD = high dose; HLA = human leukocyte antigen; IM = intramuscular; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SMR = sexual maturity rating; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine

References

Hsu AJ, Neptune A, Adams C, Hutton N, Agwu AL. Antiretroviral stewardship in a pediatric HIV clinic: development, implementation and improved clinical outcomes. Pediatr Infect Dis J. 2016;35(6):642-648. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26906161.
Maiese EM, Johnson PT, Bancroft T, Goolsby Hunter A, Wu AW. Quality of life of HIV-infected patients who switch antiretroviral medication due to side effects or other reasons. Curr Med Res Opin. 2016;32(12):2039-2046. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27552553.
Foissac F, Blanche S, Dollfus C, et Population pharmacokinetics of atazanavir/ritonavir in HIV- 1-infected children and adolescents. Br J Clin Pharmacol. 2011;72(6):940-947. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21649692.
Chokephaibulkit K, Prasitsuebsai W, Wittawatmongkol O, et al. Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged ≥7 years. Antivir Ther. 2012;17(7):1263-1269. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22954687.
Paediatric European Network for Treatment of Once vs. twice-daily lopinavir/ritonavir in HIV-1-infected children. AIDS. 2015;29(18):2447-2457. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26558544.
Gondrie IPE, Bastiaans DET, Fraaij PLA, et al. Sustained viral suppression in HIV-infected children on once-daily lopinavir/ritonavir in clinical practice. Pediatr Infect Dis J. 2017;36(10):976-980. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28475554.
Orkin C, Bernal Morell E, Tan DHS, et al. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV. 2021;8(11):e668-e678. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34656207.
Lowenthal E, Chapman J, Calabrese K, et al. Adolescent and parent experiences with long-acting injectables in the MOCHA study. Presented at: Conference on Retroviruses and Opportunistic Infections; 2022. Virtual conference. Available at: https://www.croiconference.org/abstract/adolescent-and-parent-experiences-with-long-acting- injectables-in-the-mocha-study/.
Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021;8(11):e679-e689. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34648734.
Waters L, Sparrowhawk A. Clinical implementation of long-acting antiretroviral treatment in high-income countries: challenges and advantages. Curr Opin HIV AIDS. 2022;17(3):121-126. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35439786.
Llibre JM, Hung CC, Brinson C, et Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839-849. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29310899.
Aboud M, Orkin C, Podzamczer D, et al. Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 Lancet HIV. 2019;6(9):e576- e587. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31307948.
van Wyk J, Orkin C, Rubio R, et al. Durable suppression and low rate of virologic failure 3 years after switch to dolutegravir + rilpivirine 2-drug regimen: 148-week results from the SWORD-1 and -2 randomized clinical J Acquir Immune Defic Syndr. 2020;85(3):325-330. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32675772.
Compagnucci A, Chan M, Saïdi Y, et al. Once daily integrase inhibitor (INSTI) with boosted darunavir is non-inferior to standard of care in virologically suppressed children – Week 48 results of the SMILE Penta-17 Trial. Presented at: The 11th IAS Conference on HIV Sciences; 2021. Available at: https://penta-id.org/publications/hiv-publications/hiv-trials/penta-17/once- daily-integrase-inhibitor-insti-with-boosted-darunavir-is-non-inferior-to-standard-of-care-in- virologically-suppressed-children-week-48-results-of-the-smile-penta-17-trial/.
Kuhn L, Coovadia A, Strehlau R, et al. Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial. Lancet Infect Dis. 2012;12(7):521-530. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22424722.
Coovadia A, Abrams EJ, Strehlau R, et al. Efavirenz-based antiretroviral therapy among nevirapine-exposed HIV-infected children in South Africa: a randomized clinical trial. JAMA. 2015;314(17):1808-1817. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26529159.
Murnane PM, Strehlau R, Shiau S, et Switching to efavirenz versus remaining on ritonavir- boosted lopinavir in HIV-infected children exposed to nevirapine: long-term outcomes of a randomized trial. Clin Infect Dis. 2017;65(3):477-485. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28419200.
Natukunda E, Rodriguez C, McGrath E, et al. B/F/TAF in virologically suppressed adolescents and children: two-year outcomes in 6 to <18 year olds and six-month outcomes in toddlers. Presented at: 13th International Workshop on HIV Pediatrics 2021. Virtual meeting. Available at: https://www.natap.org/2021/IAS/IAS_80.htm.
Anugulruengkitt S, Gaur, P. Kosalaraksa, A. Liberty, Y. Shao, et al. . Long-term safety & efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (E/C/F/TAF) single- tablet regimen in children and adolescents living with HIV [Abstract 4] Presented at: International Workshop on HIV Pediatrics 2021. Virtual meeting. Available at: https://www.natap.org/2021/IAS/IAS_79.htm.
Turkova A, White E, Mujuru HA, et Dolutegravir as first- or second-line treatment for HIV-1 infection in children. N Engl J Med. 2021;385(27):2531-2543. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34965338.
Amuge P, Lugemwa A, Wynne B, et al. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial. Lancet HIV. 2022;9(9):e638-e648. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36055295.
Gill M, Songane M, Herrera N, et al. Pediatric ARV optimization in a real-world setting: dolutegravir transition in Mozambique. Presented at: International Workshop on HIV Pediatrics 2021. Virtual. Available at: https://academicmedicaleducation.com/meeting/international- workshop-hiv-pediatrics-2021/abstract/pediatric-arv-optimization-real-world.
Kouamou V, Manasa J, Maposphere C, et al. Tenofovir, lamivudine and dolutegravir (TLD) among rural adolescents in Zimbabwe, a cautionary tale. Presented at: International Workshop on HIV Pediatrics 2021. Virtual. Available at: https://academicmedicaleducation.com/meeting/international-workshop-hiv-pediatrics- 2021/abstract/tenofovir-lamivudine-and-dolutegravir.
Van de Ven R, Antelman G, Masenge T, Kimambo S. Impact of ARV optimization on HIV viral load suppression among children in Tanzania. Presented at: International AIDS Society 2021. Virtual. Available at: https://theprogramme.ias2021.org/Abstract/Abstract/1498.
Bacha J, Mayalla B, Chodota M, Jiwa N, Mwita L, Campbell L. There is no substitute for hard work(ing dolutegravir): outcomes of single drug substitutions among CALHIV shifted to a dolutegravir antiretroviral regimen in Mbeya and Mwanza, Presented at: International Workshop on HIV Pediatrics 2021. Virtual. Available at: https://academicmedicaleducation.com/meeting/international-workshop-hiv-pediatrics- 2021/abstract/there-no-substitute-hard-working.
Bacha Jea. The fast and the continuous: dolutegravir-based antiretroviral therapy achieves impressive viral load suppression in CALHIV in the short- and long-term. Presented at: AIDS 2022; 2022. Available at: https://programme.aids2022.org/Abstract/Abstract/?abstractid=2849
Rodriguez C, Strehlau R, Chokephaibulkit K, et al. One year outcome of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed children ≥ 2 years weighing 14 to < 25kg. Presented at: Internataional Workshop on HIV & Pediatrics 2022. Montreal, Canada. Available at: https://www.natap.org/2022/IAC/IAC_90.htm.
Gaur AH, Cotton MF, Rodriguez CA, et Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial. Lancet Child Adolesc Health. 2021;5(9):642-651. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34302760.
Phongsamart W, Jantarabenjakul W, Chantaratin S, et al. Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. J Int AIDS Soc. 2022;25(1):e25862. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35001501.
Melvin AJ, Yee KL, Gray KP, et Pharmacokinetics, tolerability, and safety of doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination tablets in adolescents living with HIV: week 24 results from IMPAACT 2014. J Acquir Immune Defic Syndr. 2023;92(2):153-161. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36215957.
Vigano A, Aldrovandi GM, Giacomet V, et al. Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected Antivir Ther. 2005;10(8):917-924. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16430197.
Fabiano V, Giacomet V, Vigano A, et Long-term body composition and metabolic changes in HIV-infected children switched from stavudine to tenofovir and from protease inhibitors to efavirenz. Eur J Pediatr. 2013;172(8):1089-1096. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23636286.
Rosso R, Nasi M, Di Biagio A, et Effects of the change from stavudine to tenofovir in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy: studies on mitochondrial toxicity and thymic function. Pediatr Infect Dis J. 2008;27(1):17-21. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18162932.
Aurpibul L, Puthanakit T, Sirisanthana T, Sirisanthana Haematological changes after switching from stavudine to zidovudine in HIV-infected children receiving highly active antiretroviral therapy. HIV Med. 2008;9(5):317-321. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18331562.
Gonzalez-Tome MI, Amador JT, Pena MJ, Gomez ML, Conejo PR, Fontelos Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children. BMC Infect Dis. 2008;8:144. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18945352.
Arribas JR, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014;14(7):581-589. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24908551.
Martinez E, Larrousse M, Llibre JM, et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS. 2010;24(11):1697-1707. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20467288.
Curran A, Martinez E, Saumoy M, et Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS. 2012;26(4):475-481. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22112606.
Bagella P, Squillace N, Ricci E, et al. Lipid profile improvement in virologically suppressed HIV-1- infected patients switched to dolutegravir/abacavir/lamivudine: data from the SCOLTA project. Infect Drug Resist. 2019;12:1385-1391. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31213857.
Calza L, Colangeli V, Borderi M, et al. Improvement in insulin sensitivity and serum leptin concentration after the switch from a ritonavir-boosted PI to raltegravir or dolutegravir in non-diabetic HIV-infected patients. J Antimicrob Chemother. 2019;74(3):731-738. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30541118.
Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020;33(1):10-19. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31789693.
Sokhela ADVANCE trial: DTG + TDF or TAF vs EFV 1st Line ART excess weight gain with DTG- TAF. Presented at: International Workshop on HIV & Pediatrics 2020; 2020. Virtual conference.
Dirajlal-Fargo S, Koay WLA, Levy ME, Monroe AK, Castel AD, Rakhmanina Effect of integrase inhibitors on weight gain in children and adolescents with HIV. Abstract 826. Presented at: Conference on Retroviruses and Opportunistic Infections; 2020. Boston, MA. Available at: https://www.croiconference.org/abstract/effect-of-integrase-inhibitors-on-weight-gain-in- children-and-adolescents-with-hiv/.
Yeoh DK, Campbell AJ, Bowen Increase in body mass index in children with HIV, switched to tenofovir alafenamide fumarate or dolutegravir containing antiretroviral regimens. Pediatr Infect Dis J. 2021;40(5):e215-e216. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33847305.
Mallon PW, Brunet L, Hsu RK, et al. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc. 2021;24(4):e25702. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33838004.
McComsey GA, Lupo S, Parks D, et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018;32(4):477-485. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29239893.
Soriano V, Fernandez-Montero JV, Benitez-Gutierrez L, et Dual antiretroviral therapy for HIV infection. Expert Opin Drug Saf. 2017;16(8):923-932. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28621159.
Arribas JR, Girard PM, Paton N, et al. Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials. HIV Med. 2016;17(5):358-367. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26709605.
Brenner BG, Thomas R, Blanco JL, et al. Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. J Antimicrob Chemother. 2016;71(7):1948-1953. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27029845.
Wijting IEA, Wit F, Rokx C, et Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy. EClinicalMedicine. 2019;17:100210. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31891143.
Rokx C, Schurink CA, Boucher CA, Rijnders BJ. Dolutegravir as maintenance monotherapy: first experiences in HIV-1 patients. J Antimicrob Chemother. 2016;71(6):1632-1636. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26888910.
Pinnetti C, Lorenzini P, Cozzi-Lepri A, et al. Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r-based antiretroviral regimen in persons with suppressed HIV replication. J Int AIDS Soc. 2014;17(4 Suppl 3):19809. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25397553.
Santos JR, Llibre JM, Bravo I, et al. Short communication: efficacy and safety of treatment simplification to lopinavir/ritonavir or darunavir/ritonavir monotherapy: a randomized clinical trial. AIDS Res Hum Retroviruses. 2016;32(5):452-455. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26781004.
Kosalaraksa P, Ananworanich J, Puthanakit T, et al. Long-term lopinavir/ritonavir monotherapy in HIV-infected children. Pediatr Infect Dis J. 2013;32(4):350-353. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23190774.
Griffith DC, Farmer C, Gebo KA, et al. Uptake and virological outcomes of single- versus multi- tablet antiretroviral regimens among treatment-naive youth in the HIV Research HIV Med. 2019;20(2):169-174. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30561888.
Natukunda E, Gaur A, Kosalaraksa P, et al. Safety, efficacy, and pharmacokinetics of single-tablet elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed, HIV- infected children: a single-arm, open-label trial. Lancet Child Adolescent Health. 2017;1(1):27-34. Available at: https://www.sciencedirect.com/science/article/pii/S2352464217300093?via%3Dihub.
Liberty A, Strehlau R, Rakhmanina N, et al. Acceptability & palatability of low dose B/F/TAF & E/C/F/TAF in children (≥2y) with Presented at: International Workshop on HIV & Pediatrics 2020; 2020. Virtual. Available at: https://academicmedicaleducation.com/meeting/international-workshop-hiv-pediatrics- 2020/abstract/acceptability-palatability-low-dose.
Rotsaert A, Nostlinger C, Collin O, et al. Acceptability of a new 4-in-1 abacavir/lamivudine/lopinavir/ritonavir paediatric fixed-dose combination: the caregiver-child dyad’s perspective. Presented at: International Workshop on HIV & Pediatrics 2020; 2020. Virtual. Available at: https://academicmedicaleducation.com/meeting/international-workshop- hiv-pediatrics-2020/abstract/acceptability-new-4-1.
Agwu AL, Fairlie Antiretroviral treatment, management challenges and outcomes in perinatally HIV-infected adolescents. J Int AIDS Soc. 2013;16:18579. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23782477.
Wensing AM, Calvez V, Gunthard HF, et al. 2015. Update of the drug resistance mutations in HIV-1. Top Antivir Med. 2015;23(4):132-141. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26713503.
Dehority W, Deville JG, Lujan-Zilbermann J, Spector SA, Viani Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents. Int J STD AIDS. 2013;24(7):549-553. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23970770.
Tobin NH, Learn GH, Holte SE, et Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus. J Virol. 2005;79(15):9625-9634. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16014925.
Kuritzkes DR. Preventing and managing antiretroviral drug resistance. AIDS Patient Care STDS. 2004;18(5):259-273. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15186710.