Treatment

Antiretroviral Therapy

• ART is recommended for all HIV infected individuals regardless of CD4 count to decrease morbidity & mortality associated w/ HIV infectionda
• Urgent initiation of ART is recommended in the following individuals:
  • Pregnant women
  • HIV w/ coinfections (HBV, HCV, active tuberculosis)
  • AIDS-defining illness, including HIV associated dementia (HAD) & AIDS-associated malignancies
  • HIV-associated nephropathy (HIVAN)
  • Low CD4 counts (eg <200 cells/mm³)
  • Acute opportunistic infections (eg cryptosporidiosis, microsporidoisis & progressive multifocal leukoencephalopathy), as well as in patients w/ early/acute infections
  • HIV HBV w/ evidence of chronic liver disease
• ART is also recommended for serodiscordant couples
• When initiating ART, it is important to educate patients about its benefits & considerations in order to optimize compliance to therapy

• All pregnant & breastfeeding women w/ acute or recent HIV infection should start ART regimen as soon as possible to prevent mother-to-child transmission
• Principles of active TB treatment in HIV-infected patients are the same as those for HIV-uninfected patients
  • All HIV patients coinfected w/ active TB should be immediately started on TB treatment
  • CD4 counts <50 cells/mm³: Start ART w/in 2 weeks of TB treatment
  • CD4 counts ≥50 cells/mm³ w/ severe clinical disease: Start w/in 2-4 weeks of TB treatment
  • CD4 counts ≥50 cells/mm³ w/o severe clinical disease: ART may be started w/in 8-12 weeks of TB treatment
• In patients w/ HBV coinfection, ART drugs active against HBV should be continued even in the setting of HIV virologic failure
  • The drug active against HBV should be continued & combined w/ other suitable ART agents to achieve HIV suppression
• Concurrent treatment of HIV and hepatitis C (HCV) infection may be complicated by overlapping drug toxicities & high pill burden
  • Decision to start HCV treatment should consider medical need for such treatment based on HCV stage
• ART is recommended in patients >50 years of age regardless of CD4 count because immunologic response to ART may be reduced in older HIV-infected patients & the risk of non-AIDS complications may increase
• ART is recommended for all individuals w/ HIV-1 infection & should be offered to those w/ early HIV-1 infection, although definitive data to confirm whether this approach will result in long-term virologic, immunologic, or clinical benefits are lacking
• If treatment is initiated in a patient w/ early HIV-1 infection, the goal is to suppress plasma HIV-1 RNA to undetectable levels
• In patients w/ early HIV-1 infection in whom therapy is initiated, testing for plasma HIV-1 RNA levels, CD4 T lymphocyte counts, & toxicity monitoring should be performed as described for patients w/ chronic HIV-1 infection
• Genotypic drug resistance testing should be performed before initiation of ART to guide the selection of the regimen
• In patients w/o transmitted drug resistant virus, therapy should be initiated w/ one of the combination regimens for patients w/ chronic HIV-1 infection
• ART can be initiated before drug resistance test results are available
• Patients starting ART should be willing & able to commit to treatment & should understand the possible benefits & risks of therapy & the importance of adherence

• Selection of treatment regimen should be individualized based on virologic efficacy, toxicity, potential drug-drug interaction, dosing frequency, pill burden, resistance testing results, comorbidities, patient characteristics (eg pregnancy potential, adherence potential) & needs
• First-line agents should include 2 NRTIs plus an NNRTI
• Second-line agents should include 2 NRTIs plus a Ritonavir-boosted PI (eg ATV/r & LPV/r)
• Third-line agents should include new drugs w/ minimal potential for cross-resistance w/ prior regimens (eg integrase inhibitors, 2nd-generation NNRTIs and PIs)

• Advantage: Have demonstrated virologic potency & durability
• Disadvantage: Prevalence of NNRTI-resistant viral strains in ART-naive patients & the low genetic barrier of these agents for the development of resistance
  • All NNRTIs except for Etravirine (ETV) require only a single gene mutation to confer resistance; cross resistance among these NNRTIs are common
• A singe tablet formulation consisting of EFV, Tenofovir (TDF) & Emtricitabine (FTC) allows one-tablet, once-daily dosing & is currently the preferred NNRTI-based regimen
  • Regimen consisting of RPV/TDF/FTC is only an alternative due to the limited data on durability to response & lower virologic response to RPV

• Requires 3-times daily dosing & has the least supporting data in clinical trials
• Appears to have the least antiviral activity & as such is not recommended as part of an initial ART regimen

• Adverse Reactions
  • Dermatologic effect (rash); CNS effects (headache, depressive symptoms, fever, anxiety); GI effects (N/V, diarrhea, abdominal pain); Endocrine & metabolic effects (elevated transaminases, amylase & bilirubin levels); Hematologic effects (increased prothrombin time, decreased hemoglobin level)
• Special Instructions
  • May be administered w/ or w/o food
  • Rash occurs frequently & may require discontinuation of therapy; usually occurs w/in 1-3 wks & lasts <2 wks. Most patients may resume therapy following a treatment interruption
  • Concurrent use of Astemizole, Terfenadine, ergot derivatives, Cisapride, Pimozide, Alprazolam, Midazolam, Triazolam is contraindicated

• Dosage Guidelines
  • 400 mg PO 8 hrly

• Adverse Reactions
  • Dermatologic effect (rash including Stevens-Johnson syndrome & erythema multiforme, pruritus); CNS effects (dizziness, headache, insomnia, somnolence, abnormal dreams, fatigue, impaired concentration, depression, anxiety, psychosis, amnesia, ataxia); GI effects (nausea, less frequently vomiting, diarrhea, hepatitis, abdominal pain); Other effects (gynecomastia, blurred vision)
• Special Instructions
  • Discontinue use if severe skin rash or fever develops
  • Contraindicated in severe hepatic impairment
  • Use w/ caution in renal impairment & in mild to moderate liver disease; monitor liver enzymes & cholesterol level
  • Use w/ caution in known or suspected hepatitis B infection, in those w/ history of mental illness, seizures

• Dosage Guidelines
  • 600 mg PO 24 hrly on an empty stomach

• Advantage: Has in-vitro activity against some viruses w/ mutations that confer resistance to DLV, EFV, & Nevirapine (NVP)
• Disadvantage: In RPV-treated patients, presence of RPV-resistant mutations at virologic failure is common & may confer cross-resistance to ETV

• Adverse Reactions
  • Dermatologic effect (rash); GI effects (N/V, abdominal pain); Metabolic effects (elevated total cholesterol, hyperglycemia, increased ALT & creatinine levels); CV effect (hypertension); CNS effect (peripheral neuropathy)
  • May cause fat redistribution & immune reconstitution syndrome
• Special Instructions
  • Should be taken w/ food; swallow whole, do not crush
  • Discontinue use if severe skin rash develops
  • Unboosted protease inhibitors (ie w/o low-dose Ritonavir) should not be used w/ Etravirine

• Dosage Guidelines
  • 200 mg PO 12 hrly after meals

• Advantage: May be used as an acceptable NNRTI option in women w/ baseline CD4 counts of <250 cells/mm³ or in men w/ pretreatment CD4 counts <400 cells/mm³
• Disadvantage: Serious hepatic events have been observed when started in ART-naive patients
  • However, patients who experience increases in CD4 count to levels above the aforementioned thresholds can safely continue w/o an increased risk for hepatic events
  • Monitoring of serum transaminases at baseline, 2 weeks after dose increase & then monthly for the first 18 weeks are recommended by some experts

• Adverse Reactions
  • Dermatologic effect (rash); GI effects (N/V, abnormal liver function tests, diarrhea, abdominal pain); CNS effects (headache, fatigue)
• Special Instructions
  • May be taken w/ or w/o food
  • Re-introduce at a lower dose for the first 14 days if treatment is interrupted for >7 days
  • Contraindicated in severe hepatic impairment
  • Interrupt treatment if severe hepatotoxicity or life-threatening skin reactions develop
  • Use w/ caution in renal or hepatic insufficiency; monitor liver function periodically

• Dosage Guidelines
  • Initial dose: 200 mg PO 24 hrly x 14 days
  • Maintenance dose: 200 mg PO 12 hrly

• May be used in combination w/ NRTIs for ART-naive patients w/pre-treatment viral load <100,000 copies/mL
• Use of RPV w/ TDF/FTC should be limited to ART-naive patients w/ pre-treatment viral load copies of <100,000 & CD4 count >200 cell/mm³
• Advantage: A once daily dosing & is coformulated w/ TDF/TFC; Compared w/ EFV, drug discontinuations w/ RPV due to adverse effects (eg dizziness, abnormal dreams, hyperlipidemia & rash) were less frequent
  • Frequency of depressive disorders & discontinuations secondary to depression are similar between RPV & EFV
• Disadvantage: Lower virologic response compared w/ EFV in patients w/ high baseline viral loads & requires acid to have an adequate absorption

• Adverse Reactions
  • CNS effects (depression, dysphoria, mood changes, negative thoughts, suicidal ideation, headache, insomnia); Dermatologic effect (rash); Endocrine & metabolic effects (increased LDL, total cholesterol & triglyceride levels); Hepatic effects (elevated liver transaminases & bilirubin levels); Renal effect (elevated creatinine level)
• Special Instructions
  • Administer w/ food 
  • Concurrent use of Carbamazepine, Dexamethasone (>1 dose), Oxcarbazepine, Phenobarbital, Phenytoin, PPIs, Rifabutin, Rifampin, Rifapentine, St. John’s wort is contraindicated

• Dosage Guidelines
  • 25 mg PO 24 hrly

^​1 Combinations of NNRTIs & NRTIs are available. Specific prescribing information may be found in the latest MIMS.

² Drug interactions listed above may not be comprehensive. Please see the latest MIMS for complete drug interaction & full prescribing information.

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• Have demonstrated durability & virologic potency in ART-naive patients
• Resistance mutations are seldom detected at virologic failure, unlike NNRTI- & Integrase Strand Transfer Inhibitor (INSTI)-based regimens
• PIs cause dyslipidemia including elevated triglycerides (TG) & high cholesterol along w/ a redistribution in body fat
• They also cause hyperglycemia

Amprenavir (APV)

• Adverse Reactions
  • CNS effects (tremors, mood disorders, oral or perioral paresthesia); GI effects (N/V, diarrhea); Endocrine effects (dyslipidemia, redistribution of body fat, buffalo hump, facial atrophy, breast enlargement); Dermatologic effect (rash)
• Special Instructions
  • May be taken w/ or w/o food, but do not take w/ a high-fat meal
  • Contraindicated in sulfonamide allergy, renal or hepatic failure, concomitant Metronidazole or Disulfiram therapy
  • Use w/ caution in diabetes mellitus (DM), when patient is on Sildenafil & vit E supplement
  • Use oral solution only when capsule & other PIs are not therapeutic options
  • Potentially fatal interactions w/ drugs w/ narrow therapeutic index (eg Cisapride, Terfenadine, Pimozide, Guanidine, Rifampicin)
• Dosage Guidelines
  • Capsules:
    • Combined w/ Ritonavir: 600 mg PO 12 hrly
    • Combined w/ other antiretrovirals: 1200 mg PO 12 hrly
  • Oral soln:
    • 17 mg/kg PO 8 hrly
    • Max dose: 2.8 g/day

• Adverse Reactions
  • GI effects (diarrhea, abdominal pain, N/V, constipation); CNS effect (headache); Other effects (nasopharyngitis, lipodystrophy)
  • May exacerbate DM & hyperglycemia
  • May impair ability to drive or operate machineries
• Special Instructions
  • Take w/ food
  • Use w/ caution in patients w/ sulfonamide allergy & hemophilia, liver disease

• Dosage Guidelines
  • Treatment naive: 800 mg w/ Ritonavir 100 mg 24 hrly
  • Treatment experienced: 600 mg 12 hrly w/ Ritonavir 100 mg 12 hrly

• Adverse Reactions
  • GI effects (N/V); Dermatologic effects (rash, severe or life-threatening skin reactions have been reported); CNS effect (headache)
  • Exacerbation of DM, hyperglycemia, immune reconstitution syndrome, fat redistribution have been reported
• Special Instructions
  • May be taken w/ or w/o food
  • Contraindicated in patients w/ previously demonstrated clinically significant hypersensitivity reactions (eg Stevens-Johnson syndrome) to any components of this product or to Amprenavir
  • Discontinue in severe rash & for moderate rashes accompanied by systemic symptoms
  • Concurrent administration of drugs that are highly dependent on CYP3A4 for clearance & for which elevated plasma levels are associated w/ serious or life-threatening events (eg Flecainide, Propafenone, Rifampin, ergot derivatives, Cisapride, St. John’s wort, Lovastatin, Simvastatin, Pimozide, Midazolam, Triazolam, Delavirdine) is contraindicated
  • Use w/ caution in patients w/ known sulfonamide allergy, underlying hepatitis B or C or marked elevations in transaminases prior to treatment

• Dosage Guidelines
  • ART-naive patients: 
    • 1400 mg PO 12 hrly or
  • Ritonavir-boosted Regimens:
    • Once-daily regimen: Fosamprenavir 1400 mg PO 24 hrly + Ritonavir 100-200 mg PO 24 hrly
    • Twice-daily regimen: Fosamprenavir 700 mg PO 12 hrly + Ritonavir 100 mg PO 12 hrly

• Adverse Reactions
  • GI effects (abdominal pain, N/V, diarrhea, regurgitation, dyspepsia, dry mouth); Metabolic effects (elevated liver enzymes, bilirubin, creatinine, phosphokinase, blood lipid levels); CNS effects (headache, dizziness, somnolence); Renal effects (nephrolithiasis, flank pain); Resp effects (cough, dyspnea); Other effects (alopecia, lipodystrophy, back pain)
  • Potentially fatal acute hemolytic anemia & acute hepatitis have been reported
• Special Instructions
  • Take on an empty stomach (best taken w/ plain water 1 hr before or 2 hr after meals)
  • Contraindicated in severe hepatic impairment
  • Use w/ caution in patients w/ increased risk of urolithiasis/nephrolithiasis, DM, hemophilia
  • Ensure adequate hydration
  • Monitor for signs of lipodystrophy
  • Concurrent administration w/ Amiodarone, Cisapride, ergot derivatives, Lovastatin, Simvastatin, Alprazolam, Midazolam, Triazolam, Pimozide, Quinidine, Rifampin, Sildenafil, St John’s wort is contraindicated

• Dosage Guidelines
  • 800 mg PO 8 hrly
  • Combined w/ Efavirenz: 1000 mg PO 8 hrly
  • Co-administered w/ Delavirdine, Itraconazole or Ketoconazole: 600 mg PO 8 hrly
  • Combined w/ Lopinavir & Ritonavir: 600 mg PO 12 hrly
  • Combined w/ Nelfinavir: 1200 mg PO 12 hrly
  • Combined w/ Nevirapine: 1000 mg PO 8 hrly
  • Combined w/ Rifabutin: 1000 mg PO 8 hrly (reduce Rifabutin to 1/2 the standard dose)

• Adverse Reactions
  • GI effects (diarrhea, nausea, flatulence); Endocrine & metabolic effects (hyperglycemia, dyslipidemia, lipodystrophy, hypertriglyceridemia, increased creatine kinase, elevated transaminases); Hematologic effects (decreased lymphocyte, neutrophil & hemoglobin counts)
• Special Instructions
  • Take w/ food
  • Concurrent administration w/ Amiodarone, Cisapride, ergot derivatives, Lovastatin, Simvastatin, Alprazolam, Midazolam, Triazolam, Pimozide, Quinidine, Rifampin, Sildenafil, St John’s wort is contraindicated
  • Use w/ caution in hepatic & renal impairment, hemophilia A or B, DM
  • Monitor for signs of lipodystrophy

• Dosage Guidelines
  • 750 mg PO 8 hrly or
  • 1250 mg PO 12 hrly

• Adverse Reactions
  • CNS effects (asthenia, fatigue, headache, dizziness, seizures, anxiety, sweating, paresthesia); CV effects (syncope, orthostatic hypotension); GI effects (dry mouth, mouth ulcers, dyspepsia, N/V, diarrhea, taste disturbance, pancreatitis); Dermatologic effects (skin rashes, pruritus); Other effects (myalgia, renal insufficiency, anemia, elevated WBC count, raised prothrombin time, lipodystrophy, electrolyte imbalance)
  • Potentially fatal hypersensitivity reactions, anaphylaxis, Stevens-Johnson syndrome have been reported
• Special Instructions
  • Take w/ food
  • Contraindicated in severe hepatic impairment
  • Use w/ caution in DM, hemophilia, pancreatitis
  • Discontinue treatment if patient develops hemolytic anemia
  • Monitor levels of glucose, lipid, uric acid & blood count
  • Ensure adequate hydration to reduce risk of nephrolithiasis

• Dosage Guidelines
  • 600 mg PO 12 hrly
  • Initial dose: No <300 mg PO 12 hrly x 3 days then increase dose by 100 mg PO 12 hrly at 2-3 day intervals up to the recommended dose of 600 mg PO 12 hrly over a period of not >14 days
  • Dosing for PI-based regimens, please refer to dosages of other Protease Inhibitors

• Adverse Reactions
  • GI effects (N/V, diarrhea, taste disturbances, abdominal pain, anorexia, flatulence); CNS effects (asthenia, fatigue, sleep disturbances, headache, dizziness, paresthesia, hypoesthesia); Musculoskeletal effects (myalgia, arthralgia, myositis, rhabdomyolysis); Endocrine & metabolic effects (hyperglycemia, onset or exacerbation of DM, irregular & prolonged heavy menstruation, sexual dysfunction); Other effects (lipodystrophy, blood disorders, ingrowing toenails & paronychia of the great toes, acute paranoid reactions)
  • Potentially fatal hypersensitivity reactions, Stevens-Johnson syndrome, photosensitivity, nephrolithiasis, pancreatitis, hemorrhage, hemolytic anemia, intracranial hemorrhage, respiratory disorder have been reported
• Special Instructions
  • Take w/ food (take at the same time as Ritonavir w/in 2 hr following a meal)
  • Contraindicated in severe hepatic impairment
  • Use w/ caution in renal & mild-moderate hepatic impairment, DM, hemophilia, underlying hepatitis B or other liver abnormalities
  • Concomitant use w/ Sildenafil, NRTIs, Pimozide may cause serious arrhythmogenic, neurologic or other toxicities

• Dosage Guidelines
  • Combined w/ Ritonavir: 1000 mg PO 12 hrly

• Adverse Reactions
  • GI effects (diarrhea, N/V, abdominal pain); CNS effects (headache, fatigue); Metabolic effects (elevated transaminsases, total cholesterol & triglyceride levels); Other effects (fever, dehydration, wt loss, myalgia, rash, dyspnea; lipodystrophy)
• Special Instructions
  • Should be taken w/ food
  • Concurrent use of ergot derivatives, Cisapride, Pimozide, sedatives, Rifampicin, HMG Co-A inhibitors, immunosuppressive agents is contraindicated
  • Use w/ caution in chronic hepatitis B or C coinfection, sulfonamide allergy, in those at increased risk of bleeding
  • Contraindicated in patients w/ pretreatment liver enzyme levels >5x the upper limit of normal
  • Monitor liver function, cholesterol & triglyceride levels before & during therapy

• Dosage Guidelines
  • Combined w/ Ritonavir: 500 mg PO 12 hrly

Boosted PI Regimens

• Ritonavir (RTV)-boosted PI-based regimens have demonstrated good immunologic & virologic responses
• Advantage: Drug resistance to most PIs require multiple mutations in the HIV protease gene & seldom develops after early virologic failure, esp when RTV boosting is used
• Disadvantage: Are often associated w/ more gastrointestinal (GI) symptoms than EFV-based regimens; like EFV-based regimens, are also associated w/ hepatic transaminase elevations
  • Other disadvantages include higher pill burden & more clinically significant drug interactions are seen w/ RTV-boosted PI regimens than w/ NNRTI-based regimens

• ATV/r & ATV/c combined w/ TDF/FTC are recommended as alternative regimens for ART-naive patients regardless of pre-treatment HIV RNA
• ATV/c + TDF/FTC is not recommended for patients w/ CrCl <70 mL/min
• ATV/r or ATV/c + ABC/3TC is recommended as other regimen
  • Its use is limited to patients w/ pre-ART HIV RNA <100,000 copies/mL
• Advantage: A clinical trial has shown RTV-boosting of ATZ enhances ATV concentration, improving virologic activity as compared w/ ATV alone
• Disadvantage: Main adverse effect is indirect hyperbilirubinemia that is not associated w/ hepatic transaminase elevation; also requires acidic gastric pH for dissolution; thus, antacids, H2 agonists & proton pump inhibitors (PPI) may impair its absorption

• Regimen consisting of DRV/r + TDF/FTC is also a preferred PI-based regimen
  • ARTEMIS study has shown DRV/r, compared w/ LPV/r (both in combination w/ TDF/FTC), to have a superior virologic response

• Recommended as an alternative PI-based regimen, w/ once- or twice-daily dosing
• Studies have shown similar CD4 & virologic benefits when compared w/ ATV/r, both in combination w/ TDF/FTC

• Associated w/ high incidence of nephrolithiasis
• Indinavir requires high fluid intake

• Is the only available coformulated boosted PI
• An alternative PI-based regimen for ART-naive patients
• Compared w/ other PIs boosted w/ 100 mg/daily of RTV, LPV/r should be boosted w/ 200 mg/day of RTV
• Associated w/ higher rates of GI side effects & hyperlipidemia
• Once-daily LPV/r should not be given to patients who have HIV mutations associated w/ PI resistance
• Twice-daily dosing is preferred for pregnant women, esp during 3rd trimester, when LPV levels are expected to decline

• Adverse Reactions
  • GI effects (diarrhea, N/V, abdominal pain); CNS effect (headache); Metabolic effects (elevated liver enzyme, total cholesterol & triglyceride levels)
• Special Instructions
  • Tab: May be taken w/ or w/o food
  • Oral soln: Should be taken w/ food
  • Once-daily administration is not recommended in therapy-experienced patients
  • Concurrent use of ergot derivatives, Cisapride, Pimozide, sedatives, Rifampicin, HMG Co-A inhibitors is contraindicated
  • Use w/ caution in pancreatitis, hepatic impairment, hemophilia
  • See also Ritonavir Special Instructions

• Dosage Guidelines
  • ART-naive: 400/100 mg PO 12 hrly (two 200/50 mg tab or 5 ml oral soln) or
  • 800/200 mg PO 24 hrly (four 200/50 mg tab or 10 ml oral soln)
  • ART-experienced, concomitant therapy w/ EFV, NVP: 6.5 ml (Lopinavir 533 mg/Ritonavir 133 mg) oral soln 12 hrly  Lopinavir + Ritonavir (LPV/r)

• Has a high pill burden & requires twice-daily dosing & 200 mg of RTV
• At recommended dose, this regimen is associated w/ increases in both PR & QT prolongation
  • Degree of QT prolongation is greater than that seen w/ some other boosted PI
  • ECG is recommended prior to its initiation
• May be an acceptable regimen but should be used w/ caution against certain ART-naive patients (contraindicated in patients w/ QT prolongation, complete AV block, refractory hypokalemia or hypomagnesemia)

• Remains a good alternative dual-NRTI option for some ART-naive patients
• Should only be given to patients who tested negative for HLA-B*5701
• Abacavir has the potential for serious hypersensitivity reactions
• The fixed dose combination allows for once-daily dosing
• Should be used w/ caution in patients at higher risk for cardiovascular disease & whose plasma HIV RNA levels are at ≥100,000 copies/mL

 Abacavir 600 mg/ Lamivudine 300 mg

• Adverse Reactions
  • See individual components
• Special Instructions
  • May be administered w/ or w/o food
  • See individual components
• Dosage Guidelines
• 1 tab PO 24 hrly

Acceptable Dual NRTI  

Zidovudine (ZDV)/Lamivudine (3TC) [coformulated]

• Has extensive durability, tolerability & safety experience

• Recommended only as an acceptable regimen due to its greater toxicity than other dual NRTIs & its requirement for twice-daily dosing

Lamivudine 150 mg/ Zidovudine 300 mg

• Adverse Reactions
  • See individual components
• Special Instructions
  • May be administered w/ or w/o food
  • See individual components
• Dosage Guidelines
  • 1 tab PO 12 hrly

Triple NRTI

• Triple NRTI regimens have been shown to have suboptimal virologic activity based on several controlled trials

ABC/3TC/ZDV (coformulated)

• The only triple NRTI combination w/ available supporting randomized clinical trial data
• With comparable virologic activity to IDV- & NFV-based regimens but was inferior to EFV-based regimen
• Generally not recommended & should only be used when a preferred alternative or an acceptable NNRTI-, PI-, or INSTI-based regimen is less desirable due to toxicities, complexity of regimen or drug interactio

Abacavir 300 mg/ Lamivudine 150 mg/ Zidovudine 300 mg

• Adverse Reactions
  • See individual components
• Special Instructions
  • May be administered w/ or w/o food
  • See individual components
• Dosage Guidelines
  • 1 tab PO 12 hrly

CCR5 Antagonist-based Regimens

CCR5-Antagonist (eg Maraviroc) + 2 NRTIs (Zidovudine/Lamivudine)

• Maraviroc (MVC) is recommended only as an acceptable regimen for ART-naive patients due to its limited experience w/ regimens other than ZDV/3TC, its cost (requires tropism assay prior to use), & requirement for twice-daily dosing

Other Antiretroviral Regimens for Initial Therapy when Abacavir or Tenofovir Cannot be Used

Darunavir/Ritonavir + Raltegravir (DRV/r + RAL)

• Considered in patients w/ HIV RNA <100,000 copies/uL, CD4 cell counts >200/mm³ & those who cannot take either TDF or ABC

Lopinavir/Ritonavir + Lamivudine (LPV/r + 3TC)

• Recommended as initial therapy when both TDF & ABC are contraindicated

Recommended Antiretroviral Drug Regimens for Antiretroviral Naive Patients

Adapted from: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents 2016.
1 3TC may be substituted for FTC & vice-versa
2 Once daily LPV/r is not recommended in pregnant patients

Efavirenz 600 mg/ Emtricitabine 200 mg/Tenofovir 300 mg

• Adverse Reactions
  • See individual components
• Special Instructions
  • Should be taken on an empty stomach (dosing at bedtime to improve tolerability of nervous system symptoms)
  • See individual components
• Dosage Guidelines
  • 1 tab PO 24 hrly

Rilpivirine 25 mg/Emtricitabine 200 mg/Tenofovir 300 mg

• Adverse Reactions
  • See individual components
• Special Instructions
  • Administer w/ meals (preferably high fat)
  • See individual components
• Dosage Guidelines
  • 1 tab PO 24 hrly

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Other Antivirals ¹

Enfuvirtide (T20)

• Adverse Reactions
  • GI effects (diarrhea, nausea, abdominal pain); CNS effects (fatigue, insomnia); Local effects (pain, infection, erythema at site of inj)
• Special Instructions
  • Local inj site reactions are common. Administration using a needle-free device has been associated w/ nerve pain, bruising, & hematomas at sites when large nerves are close to the skin; administer only in recommended sites
  • Use w/ caution in patients w/ coagulation disorders or in those receiving anticoagulants due to increased risk of bleeding at inj site
• Dosage Guidelines 
  
  • Adults & Childn >16 yr: 90 mg SC 12 hrly

 

Maraviroc (MVC)

• Adverse Reactions
  • GI effects (GI disorders, dysgeusia); CNS effects (dizziness, asthenia, somnolence, paresthesia, insomnia); Other effects (increased transaminases, rash, pruritus, back pain, muscle spasms)
• Special Instructions
  • May be taken w/ or w/o food
  • Use w/ caution in patients w/ renal or hepatic impairment, patients at risk for CV events, history of postural hypotension
• Dosage Guidelines
  • 150 mg PO 12 hrly or
  • 300 mg PO 12 hrly or
  • 600 mg PO 12 hrly

 

¹ Drug interactions listed above may not be comprehensive. Please see the latest MIMS for complete drug interaction & full prescribing information.

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Management of Patients w/ Treatment Failure

Consider expert referral for all patients who experience treatment failure 

General Approach to Patients w/ Virologic Failure

• Evaluation should include assessment of adherence, drug-drug or drug-food interaction, drug tolerability & severity of the patient’s HIV disease, history of ART, concomitant medications, results of prior drug resistance testing, & CD4 & HIV RNA counts over time
  • Identify possible clinical scenario involved in treatment failure (eg patient adherence, timing of the drug resistance test, presence of a highly drug resistant HIV)
• Goal of treatment in ART-experienced patients w/ drug resistance who are experiencing failure is to re-establish virologic suppression (<48 copies/mL)
• Change the ART regimen as soon as virologic failure is confirmed
  • There is no consensus for the optimal time to change therapy
  • Patients who failed 2nd-line agents w/o new antiretroviral options should continue w/ a tolerated regimen
  • The goal is to suppress HIV replication to a level where drug resistance mutations do not emerge
• To establish a new ART regimen, review patient’s treatment history, including results of both past & current resistance tests, & identify at least 2 (preferably 3) fully active agents to combine w/ an optimized background ART regimen
  • Fully active agents are those that are likely to have virologic activity based on the patient’s drug resistance test results, treatment history & the drug’s mechanism of action
  • Adding a single fully active agent is not recommended since this increases the risk of rapid development of resistance
  • But in patients w/ a high chance of clinical progression & limited drug options, adding a single drug regimen may reduce risk of immediate clinical progression
• Interrupting or discontinuing treatment is not recommended since this may lead to rapid decline in the CD4 count & rise in HIV RNA & may increase the risk for clinical progression
• In cases of patients that are highly ART experienced, where maximal virologic response is not possible, ART should be continued w/ regimens that are designed to preserve CD4 cell counts, avoid clinical progression, & minimize toxicity
• In patients with limited drug choices & a high likelihood of clinical progression (eg CD4 count <100 cells/mm³), adding a single ART agent may reduce the risk of immediate clinical progression
  • May produce transient increases in CD4 cell counts &/or decreases in HIV RNA which have been associated w/ clinical benefits

 

Management of Immunologic Failure

• Focus on patients w/ CD4 counts <200 cells/mm³
• Currently, it is not clear if immunologic failure in the setting of virologic suppression should prompt a change in the ART regimen; various strategies are still under investigation
  • Immune-based therapies should not be used except for clinical trials

 

All dosage recommendations are for non-pregnant & non-breastfeeding women, non-elderly adults w/ normal renal & hepatic function unless otherwise stated.

Not all products are available or approved for above use in all countries. 

Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information.

Click the link below for specific prescribing information of products available in respective countries.

Brands available in:   Hong Kong      Indonesia       Malaysia      Philippines     Singapore     Thailand     Vietnam


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