Antiretroviral treatment for HIV infection: Swedish recommendations 2019

Figures & data

Table 1. Registered ARVs in Sweden including yearly cost (January 2019).

Generic name	Abbreviation	Brand name	Cost (360 d), USD^a
Nucleoside reverse transcriptase inhibitors (NRTI)
Abacavir	ABC	Ziagen	3111
Didanosine	ddI	Videx	*
Emtricitabine	FTC	Emtriva	2465
Lamivudine	3TC	Epivir, lamivudine^b	1664
Stavudine	d4T	Zerit	*
Tenofovir disoproxil fumarat	TDF	Viread, Tenofovir disoproxil^b	91
Tenofovir alafenamide	TAF	Vemlidy	5490
Zidovudine	AZT/ZDV	Retrovir	1679
Fixed combinations	ABC + 3TC	Kivexa, abacavir/lamivudine^b	1957
	TDF + FTC	Truvada, emtricitabine/tenofovir disoproxil fumarate^b	154
	TAF + FTC	Descovy	5654
	AZT + 3TC	Combivir, lamivudine/zidovudine^b	4387
	AZT + 3TC + ABC	Trizivir	7193
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Efavirenz	EFV	Stocrin/efavirenz^b	129
Nevirapine	NVP	Viramune, nevirapine^b	219
Etravirine	ETR	Intelence	4867
Rilpivirine	RPV	Edurant	3238
Doravirine	DOR	Pifeltro	4501
Fixed combinations	EFV + TDF + FTC	Efavirenz/emtricitabine/tenofovir disoproxil fumarate^b	398
	RPV + TDF + FTC	Eviplera	10,612
	RPV + TAF + FTC	Odefsey	10,099
	RPV + DTG	Juluca	9652
	DOR + TDF + 3TC	Delstrigo	9597
Protease inhibitors (PI)
Atazanavir	ATV	Reyataz	5665
Darunavir	DRV	Prezista, darunavir^b (800 mg × 1)	5515
		Prezista, darunavir^b (600 mg × 2)	8332
Fosamprenavir	fAPV	Telzir	4265
Indinavir	IDV	Crixivan	3743
Lopinavir fixed combination	LPV + RTV	Kaletra	5247
Ritonavir (100 mg × 1)	RTV	Norvir, ritonavir^b	397
Tipranavir	TPV	Aptivus	9678
Fixed combinations	ATV + cobicistat	Evotaz	5669
	DRV + cobicistat	Rezolsta	5910
	DRV + cobicistat + TAF + FTC	Symtuza	10,361
Integrase inhibitors (INSTI)
Dolutegravir	DTG	Tivicay	6399
Raltegravir	RAL	Isentress (400 mg 1 × 2 and 600 mg 2 × 1)	7059
Elvitegravir	EVG	Vitekta	*
Bictegravir	BIC + TAF + FTC	Biktarvy	11,651
Fixed combination	DTG + ABC + 3TC	Triumeq	11,353
	EVG + cobicistat + TDF + FTC	Stribild	12,527
	EVG + cobicistat + TAF + FTC	Genvoya	12,092
	DTG + RPV	Juluca	9651
Fusion inhibitors (FI)
Enfuvirtide	T-20	Fuzeon	19,226
CCR5-inhibitors
Maraviroc (150/300 mg × 2)	MVC	Celsentri (150/300 mg × 2)	10,979

^aThe Swedish pharmacy procurement price (‘AIP’) for standard adult doses (exchange rate as of 13 December 2012 where 1 USD = 9,38 SEK). The price of PI includes recommended dose of ritonavir. The first-line treatment in bold for comparison. For further information on the medicines, see SPCs or www.emea.europa.eu. *Not available in Sweden (January 2019).

^bAvailable as generic.

Table 2. Levels of evidence and recommendation (http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/).

Quality grading of evidence base

1a Systematic review (with homogeneity) of randomized controlled trials

1b Individual randomized controlled trials with narrow confidence intervals

1c ‘All or none’ all patients died before the treatment became available, but  some now survive on it; or when some patients died before the  treatment became available, but none now die on it

2a Systematic review (with homogeneity) of cohort studies

2b Individual cohort study (including low quality RCT; e.g. <80% follow-up)

2c ‘Outcomes’ Research; Ecological studies

3a Systematic review (with homogeneity) of case–control studies

3b Individual Case–Control Study

4 Case-series (and poor quality cohort and case–control studies)

5 Expert opinion without explicit critical appraisal, or based on physiology,  bench research or ‘first principles’

Grading of recommendations

A Based on evidence level 1a, b or c

B Based on evidence level 2a, b or c, 3a or b

C Based on evidence level 4

D Based on evidence level 5

Table 3. General laboratory monitoring.

New patients

Weight, length, blood pressure

HIV RNA, resistance markers, CD4 counts

RBC, WBC, PLT

S-Albumin, creatinine, estimated creatinine clearance, Na, K

Bilirubin, AST, ALT, ALP

Fasting B-glucose, triglycerides, cholesterol (incl. HDL, LDL)

U-albumin, U-erythrocytes, U-glucose

Syphilis serology, hepatitis serology (A + B + C)

STI-screening (offered to all patients), referral gynaecologist (women)

HLA-B*5701

Untreated patient (2–4 times/year)

Weight, blood pressure

HIV RNA, CD4 counts

RBC, WBC, PLT

Creatinine, estimated creatinine clearance, ALT, GT

STI-screening, incl. syphilis, at least once/year, offered to individuals at risk  of STI

HCV in PWID once/year and with increased liver function tests

Treated patient (2–4 times/year)

Weight, blood pressure

HIV RNA

CD4 counts (once/year enough in stable patients)

RBC, WBC, PLT

Creatinine, estimated creatinine clearance

ALT, bilirubin

Triglycerides, cholesterol, incl. HDL, LDL

STI-screening, incl. syphilis, at least once/year, offered to individuals at risk  of STI

HCV in PWID once/year and with increased liver function tests

Blood lipids (see above) is monitored the first year of new treatment  regimen, thereafter only if pathological results or if new treatment  is started

Table 4. Indicator illnesses.

STI; chlamydia, gonorrhoea, syphilis, genital ulcers, lymphogranuloma venereum

Tuberculosis

Lymphoma (all types)

Cervical and anal cancer/high-grade dysplasia

Herpes zoster at age <65 years

Hepatitis B and C, acute or chronic

Mononucleosis-like symptoms and non-specific lymphadenopathy

Anaemia, thrombocytopenia, and leucopoenia with duration of more than four weeks

Seborrhoic dermatitis / oral candidiasis

Table

Name	Formulation	Neonate	Paediatric/adolescent	Comment
Nucleoside reverse transcriptase inhibitors (NRTI)
Abacavir (ABC) Ziagen Generics available	Syrup 20 mg/ml, Film-coated tablet 300 mg (scored tablet)	Not registered < 3 months (8 mg/kg × 2 ongoing study)	Syrup: 8 mg/kg × 2 (max 300 mg × 2) Tablet: 14-21 kg, 150 mg × 2 22 kg to < 30 kg, 150 mg in the morning and 300 mg in the evening 30 kg, 300 mg × 2, alt. 600 mg × 1 Adult dose given ≥ 12 years	Dosed once daily for children ≥ 3 years. HLA B*5701 must be tested before use. Can be given with or without food.
Emtricitabine (FTC) Emtriva	Capsule 200 mg	Not registered < 3 months	≥ 33 kg, capsule 200 mg × 1 Adult dose given ≥ 12 years	Can be given with or without food.
Lamivudine (3TC) Epivir Zeffix	Syrup 10 mg/ml, Film-coated table 150 mg (scored) and 300 mg, Film-coated tablet 100 mg (Zeffix)	< 30 days, 2 mg/kg × 2	Syrup: 4 mg/kg × 2 Tablet: 14 kg for < 19 kg, 75 mg × 2 19 kg for < 25 kg, 100 mg × 2 25 kg for < 30 kg, 75 mg in the morning and 150 mg in the evening 30 kg, 150 mg × 2, alt. 300 mg × 1 Adult dose given ≥ 12 years	Dosed once daily for children ≥ 3 years Can be given with or without food.
Tenofovir disoproxil fumarate (TDF) Viread Generics available	Viread, Oral powder 33 mg/g Film-coated tablet 123 mg, 163 mg, 204 mg and 245 mg	Not registered < 2 years	Oral powder: 6,5 mg/kg × 1 (max 245 mg × 1) Tablet (6 to < 12 years): 17 kg to < 22 kg, 123 mg × 1 22 kg to < 28 kg, 163 mg × 1 28 kg to < 35 kg, 204 mg × 1 ≥ 35 kg, 245 mg × 1 Adult dose given ≥ 12 years	Should be taken with food. High fat content increases absorption. Use cautiously in younger children, pre-puberty and in combination with PI/r
Zidovudine (ZDV) Retrovir	Syrup 10 mg/ml Capsule 100 mg and 250 mg, Film-coated tablet 300 mg (scored) Solution for infusion 10 mg/ml (dilute to 2 mg/ml)	Premature: < week 30: 2 mg/kg if po and 1,5 mg/kg if iv bid, after 4 w increase dose to 3 mg resp. 2,3 mg bid w 30 to < w 35: 2 mg/kg if po and 1,5 mg/kg if iv bid, after 2 w increase dose to 3 mg resp. 2,3 mg bid Full term (≥ v 35) < 3 months, 4 mg/kg × 2 (3 mg/kg × 2 if iv)	4 kg to < 9 kg, 12 mg/kg × 2 9 kg to < 30 kg, 9 mg/kg × 2 ≥ 30 kg, 300 mg × 2 Adult dose given ≥ 12 years	Can be taken with food.
Fixed combinations
Atripla	Film-coated tablet (600/200/245 mg EFV/ FTC/TDF)		≥ 12 years and ≥ 40 kg, 1 × 1
Bictarvy	Film-coated tablet (50/200/25 mg BIC/FTC/TAF)		> 18 years, 1 × 1
Combivir	Film-coated tablet (300/150 mg ZDV/3TC)		≥ 12 years or ≥ 30 kg, 1 × 2
Descovy	Film-coated tablet (200/25 mg, 200/10 mg FTC/TAF)		≥ 6 years or ≥ 35 kg, 1 × 1
Eviplera	Film-coated tablet (200/25/245 mg FTC/RPV/TDF)		≥ 18 years, 1 × 1	Use cautiously if HIV RNA > 100.000 copies/ml because of risk of virological failure
Genvoya	150 mg/150 mg/200 mg/10 mg (EVG/ COBI/ FTC/TAF)		≥ 12 years or ≥ 35 kg, 1 × 1
Kivexa Generics available	Film-coated tablet (600/300 mg ABC/3TC)		≥ 12 years or ≥ 30 kg, 1 × 1	The Arrow study indicates that Kivexa can be given to children ≥ 25 kg
Odesfey	Film-coated tablet (200/25/25 mg FTC/TAF/RPV)		≥ 12 years or ≥ 35 kg, 1 × 1	Use cautiously if HIV RNA > 100.000 copies/ml because of risk of virological failure
Stribild	Film-coated tablet (150/150/200/245 mg EVG/COBI/FTC/TDF)		≥ 18 years, 1 × 1
Symtuza	Film-coated tablet (10/800/200/150 mg TAF/DRV/FTC/COBI)		≥ 12 years and ≥ 40 kg, 1 × 1	Given with food
Trizivir	Film-coated tablet (300/150/300 mg ABC/ 3TC/ZDV)		≥ 16 years, 1 × 2	Not first line treatment for children and adolescents
Triumeq	Film-coated tablet 50 mg/ 600 mg/ 300 mg (DLG/ABC/3TC)		≥ 12 years and ≥ 40 kg, 1 × 1
Truvada Generic available	Film-coated tablet (200/245 mg FTC/TDF)		≥ 12 years or ≥ 35 kg, 1 × 1
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Efavirenz (EFV) Stocrin Generics available	Tablet 50 mg, 200 mg and 600 mg Syrup 30 mg/ml	Not registered	Syrup to children 3 - <5 years: 13 - < 15 kg, 360 mg × 1 15 - < 20 kg, 390 mg × 1 20 - < 25 kg, 450 mg × 1 25 - < 33 kg, 510 mg × 1 Syrup to children ≥ 5 years 13 - < 15 kg, 270 mg × 1 15 - < 20 kg, 300 mg × 1 20 - < 25 kg, 360 mg × 1 25 - < 33 kg, 450 mg × 1 33 - < 40 kg, 510 mg × 1 ≥ 40 kg, 720 mg × 1 Tablets irrespective of age 10 - < 15 kg, 200 mg × 1 15 - < 20 kg, 250 mg × 1 20 - < 25 kg, 300 mg × 1 25 - < 33 kg, 350 mg × 1 33 - < 40 kg, 400 mg × 1 ≥ 40 kg, 600 mg × 1	S-concentration 14-21 days after treatment initiation. Recommended concentration 3.3 to 12.7 μmol/L 12 to 20 hours after dose intake. Should be taken without food at bedtime. Foods high in fat increase bioavailability.
Nevirapine (NVP) Viramune Generics available	Tablet 200 mg and 400 mg Slow-release tablet 50 mg and 100 mg Syrup 10 mg/ml	5 mg/kg or 120 mg/m^2 × 1 for 14 days, followed by 5 mg/kg or 120 mg/m^2 × 2 for 14 days, followed by 200 mg/m^2 × 2 (until 2 months age)	120-200 mg mg/m^2 × 2. Start with 120 mg/m^2 (max dose 200 mg) × 1 i 14 days. If there are no skin eruptions or other adverse effects, increase to full dose = < 8 years 7 mg/kg or 200 mg/m^2 × 2 (max dose, 200 mg × 2) ≥ 8 years 4 mg/kg or 120 mg/m^2 × 2 (max dose, 200 mg × 2)	NVP is initiated in low doses and increased gradually for induction of CYP450 metabolizing enzymes, resulting in increased clearance. Skin eruptions rates are decreased by the gradual increase. Can be taken with or without food.
Rilpivirine (RPV) Edurant	Film-coated tablet 25 mg		≥ 12 years with viral load ≤ 100.000 HIV-1-RNA-copies/ml	Should be taken with food. Part of fixed combination Eviplera
Protease Inhibitors (PI)
Atazanavir (ATV) Reyataz	Capsule 150 mg, 200 and 300 mg	Not registered. Not given to children < 3 months because of risk of hyperbilirubinaemia (kernicterus).	< 6 years: Not registered. Dose 6-18 years: Boosted with Ritonavir (ATV/RTV). 15 kg to < 20 kg, 150/100 mg × 1 ≥ 20 kg to < 40 kg, 200/100 mg × 1 ≥ 40 kg, 300/100 mg × 1	Should be taken with food. ATV should possibly be increased to 300 mg if ≥35 kg to avoid under dosing, especially during co-treatment with tenofovir
Darunavir (DRV) Prezista	Oral suspension 100 mg/ml Tablet: 75 mg, 150 mg, 400 mg, 600 mg and 800 mg	Not registered.	< 3 years: Not registered. Dose 3-17 years Boosted med Ritonavir (DRV/RTV) Treatment naive: 15 to < 30 kg, 400/100 mg × 1 30 to < 40 kg, 475/100 mg × 1 > 40 kg, 800/100 mg × 1 Previously treated: Syrup: 15 to < 30 kg, 380/50 mg × 2 30 to < 40 kg, 460/60 mg × 2 > 40 kg, 600/100 mg × 2 Tablet/Syrup: ≥20 to <30 kg, 375/50 mg × 2 ≥30 to <40 kg, 450/60 mg × 2 ≥40 kg, 600/100 mg × 2 Adolescent (≥ 12 years and 40 kg): 800 mg/100 mg × 1 ≥ 18 years, previously treated 600/100 mg × 2 With Maraviroc: 600/100 mg × 2 + 150 mg MVC × 2	Should be taken with food.
Lopinavir/Ritonavir (LPV/RTV) Kaletra	Tablet 200 mg LPV/50 mg RTV, Tablet 100 mg LPV/25 mg RTV, Syrup (NB! contains 42,4 % ethanol) 80 mg LPV/20 mg RTV/ml	Registered from 2 years Not together with NVP or EFV: Should not be used first weeks of live because of lacking documentation and suspected toxicity in premature children (FDA U.S. Food and Drug Administration. FDA Drug Safety Communication). Dose 14 days – 6 months age: LPV/RTV 16 /4 mg /kg × 2	Registered from 2 years Not together with NVP or EFV: 6 months – 18 years: LPV/RTV Syrup: 7 - < 15 kg, 12/3 mg /kg × 2 15 to 40 kg, 10/2,5 mg /kg × 2 > 40kg: 400/100 mg × 2 Tablet 15 - < 25 kg, 200/50 mg × 2 ≥ 25 - < 35 kg, 300/75 mg × 2 ≥ 35 kg, 400/100 mg × 2 In combination with NVP or EFV (should normally be avoided): 6 months – 18 years: 7 - < 15 kg: 13/3,25 mg /kg × 2 15 - 45 kg: 11/2,75 mg /kg × 2 600 mg LPV/150 mg RTV × 2 Tablet 15 - < 20 kg, 200/50 mg × 2 ≥ 20 - < 30 kg, 300/75 mg × 2 ≥ 30 kg - < 45 kg, 400/100 mg × 2 ≥ 45 kg, 600/150 mg × 2	Syrup should be taken with food. Tablets can be taken with or without food. If used below one year of age plasma concentration should be monitored
Ritonavir (RTV) Norvir	Film-coated tablet 100 mg, syrup 80 mg/ml			Only used as booster with other PI
Fusion inhibitors (FI)
Enfuvirtide (T-20) Fuzeon	Injection 90 mg/ml	Not registered	Not registered < 6 years. Dose 6–16 years: 2 mg/kg (max dos, 90 mg) × 2 s.c. >16 years = 90 mg × 2 s.c.
Integrase Inhibitors (INI)
Dolutegravir (DLG) Tivicay	Tablet 50 mg	Not registered	Dose ≥ 6 år: 15 kg to < 20 kg, 20 mg × 1 20 kg to < 30 kg, 25 mg × 1 30 kg to < 40 kg, 35 mg × 1 ≥ 40 kg, 1 × 1
Elvitegravir (EVG)				Part of fixed combination Stribild
Raltegravir (RAL) Isentress	Tablet 400 mg Chewable tablet 25 mg and 100 mg (scored) Granulate for syrup 100 mg	Registered from 4 weeks of age	Granulate for syrup 10 mg/ml: Birth to one week of age: 2 kg to <3 kg, 0,4 ml × 1 3 kg to < 4 kg, 0,5 ml × 1 4 kg to < 5 kg, 0,7 ml × 1 1–4 weeks: 2 kg to < 3 kg, 0,8 ml × 2 3 kg to < 4 kg, 1 ml × 2 4 kg to < 5 kg, 1,5 mL × 2 ≥ 4 weeks: 3 kg to < 4 kg, 2,5 ml × 2 4 kg to < 6 kg, 3 ml × 2 6 kg to < 8 kg, 4 ml × 2 8 kg to < 11 kg, 6 ml × 2 Chewable tablet: 11 kg to < 14 kg, 75 mg × 2 14 kg to < 20 kg, 100 mg × 2 20 kg to < 28 kg, 150 mg × 2 28 kg to < 40 kg, 200 mg × 2 > 40 kg, 300 mg × 2 Tablet 400 mg 400 mg × 2 can be given to children weighing ≥ 25 kg	Can be taken with or without food
Boosters
Cobicistat (COBI) Tybos	Film-coated tablet 150 mg		No data < 18 years