HIV infection in the elderly

Figures & data

Table 1 Antiretroviral agents for treatment of HIV infection

Drug class	Available agents generic (common abbreviation) – alphabetic order
Nucleoside reverse transcriptase inhibitor (NRTI)	Abacavir (ABC)
	Didanosine (ddI)
	Emtricitabine (FTC)
	Lamivudine (3TC)
	Stavudine (d4T)
	Tenofovir (TDF)
	Zidovudine (AZT or ZVD)
Nonnucleoside reverse transcriptase inhibitor (NNRTI)	Delavirdine (DLV)
	Efavirenz (EFV)
	Etravirine (ETR)
	Nevirapine (NVP)
Protease inhibitor (PI)	Atazanavir (ATV)
	Darunavir (DRV)
	Fosamprenavir (FPV)
	Indinavir (IDV)
	Nelfinavir (NFV)
	Ritonavir (RTV)
	Saquinavir (SQV)
	Tipranavir (TPV)
Fusion inhibitor	Enfuvirtide (T-20)
Entry inhibitor	Maraviroc (MVC; Selzentry^™; Pfizer Inc., New York, NY, USA)
Integrase inhibitor	Raltegravir (RAL; Isentress^™; Merck and Co., Inc., Whitehouse Station, NJ, USA)
Combination agents – NRTIs
Lamivudine/Zidovudine (Combivir®; GlaxoSmithKline, Research Triangle Park, NC, USA)
Abacavir/Lamivudine (Epzicom®; GlaxoSmithKline, Research Triangle Park, NC, USA)
Tenofovir/Emtricitabine (Truvada®; Gilead Sciences, Inc., Foster City, CA, USA)
Abacavir/Lamivudine/Zidovudine (Trizivir®; GlaxoSmithKline, Research Triangle Park, NC, USA)
Combination agents – NNRTI + 2 NRTIs
Efavirenz/Emtricitabine/Tenofovir (Atripla®; Bristol-Myers Squibb and Gilead Sciences, LLC, Foster City, CA, USA)
Combination agents – PIs
Lopinavir/Ritonavir (common abbreviation: LPV/r) (Kaletra®; Abbott Laboratories, North Chicago, IL, USA)

Table 2 Preferred initial treatment regimens recommended for HIV-treatment-naïve adult patients based on adult HIV treatment guidelines from US DHHSa and IAS-USAb

Preferred base	US DHHS	IAS-USA
NNRTI-Based	Efavirenz	Efavirenz OR Nevirapine
	PLUS	PLUS
	Tenofovir/Emtricitabine	Tenofovir/Emtricitabine
	OR	OR
	Abacavir/Lamivudine	Zidovudine/Lamivudine
		OR
		Abacavir/Lamivudine
PI-Based, Ritonavir boosted	Lopinavir/Ritonavir	Lopinavir/Ritonavir
	OR	OR
	Atazanavir/Ritonavir	Atazanavir/Ritonavir
	OR	OR
	Fosamprenavir/Ritonavir	Fosamprenavir/Ritonavir
	PLUS	PLUS
	Tenofovir/Emtricitabine	Tenofovir/Emtricitabine
	OR	OR
	Abacavir/Lamivudine	Zidovudine/Lamivudine
		OR
		Abacavir/Lamivudine

Abbreviations: DHHS, Department of Health and Human Services; IAS, International AIDS Society; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

a Department of Health and Human Services: Panel on Antiretroviral Guidelines for Adults and Adolescents 2008;

b Hammer et al 2006.

Table 3a Recommendations for primary prophylaxis of opportunistic infections in HIV-infected individuals based on CD4 cell count (CDC 2002)

CD4 cell count (cells/mm^3)	Opportunistic infection	Recommended primary prophylactic therapy	When primary prophylaxis can be discontinued
<200	Pneumocystis pneumonia (PCP)	DOC: TMP/SMX	CD4 > 200 cells/mm^3 for at least 3 consecutive months
		Alternatives:
		Dapsone Dapsone + Pyrimethamine (+ Leucovorin) Pentamidine, aerosolized Atovaquone
<100	Toxoplasmosisa	DOC: TMP/SMX	CD4 >200 cells/mm^3 for at least 3 consecutive months
		Alternatives:
		Dapsone + Pyrimethamine (+ Leucovorin) Atovaquone (+/− Pyrimethamine, + Leucovorin)
<50	Mycobacterium avium complex (MAC)	DOC: Azithromycin or Clarithromycin	CD4 >100 cells/mm^3 for at least 3 consecutive months
		Alternatives:
		Rifabutin Azithromycin + Rifabutin

Abbreviations: DOC, drug of choice; TMP/SMX, trimethoprim/sulfamethoxazole.

a Notes: Primary prophylaxis for toxoplasmosis is indicated when CD4 cell count is less than 100 cells/mm³ and patient is toxoplasmosis immunoglobulin G (IgG) antibody positive.

Table 3b Opportunistic infections for which secondary prophylaxis is recommended (CDC 2002)

Opportunistic infection	Recommended secondary prophylactic therapy	When secondary prophylaxis can be discontinued
Pneumocystis pneumonia (PCP)	DOC: TMP/SMX	CD4 >200 cells/mm^3 for at least 3 consecutive months
	Alternatives:
	Dapsone Dapsone + Pyrimethamine (+ Leucovorin) Pentamidine, aerosolized Atovaquone
Toxoplasmosis	DOC: Sulfadiazine + Pyrimethamine + Leucovorin	CD4 >200 cells/mm^3 for at least 6 consecutive months, completed initial therapy, and asymptomatic
	Alternatives:
	Clindamycin + Pyrimethamine + Leucovorin Atovaquone + Pyrimethamine + Leucovorin
Disseminated Mycobacterium avium complex (MAC)	DOC: Clarithromycin + Ethambutol (± Rifabutin)	CD4 >100 cells/mm^3 for at least 6 consecutive months, completed 12 months of treatment, and asymptomatic
	Alternatives:
	Azithromycin + Ethambutol (± Rifabutin)
Cytomegalovirus (CMV) infection	DOC: Ganciclovir	CD4 >100–150 cells/mm^3 for at least 6 consecutive months and no active disease
	Alternatives:
	Valganciclovir Foscarnet Cidofovir
Cryptococcosis	DOC: Fluconazole	CD4 >100–200 cells/mm^3 for at least 6 consecutive months, complete initial treatment, and asymptomatic
	Alternatives:
	Itraconazole

Table 4 Common and/or important adverse effects associated with currently available antiretroviral therapy (Manfredi 2002; Cooper et al 2007; Isentress Pl 2007; Lalezari et al 2007; Nelson et al 2007; Selzentry PI 2007; Steigbigel et al 2007; DHHS 2008; Intelence PI 2008)

Antiretroviral drug class	Antiretroviral agent	Common and/or important adverse effects	Clinical considerations
Nucleoside reverse transcriptase inhibitors (NRTIs)	Zidovudine	Nausea, vomiting, headache Anemia (macrocytic), neutropenia	Monitor CBC with differential at minimum every 3 months (more frequent if necessary) Consider EPO for anemia, GCSF for neutropenia
Note: All NRTIs have the US FDA Black Box Warning for lactic acidosis and severe hepatomegaly with steatosis; routine monitoring of lactate levels is not recommended, however check levels if patient has signs or symptoms suspicious for lactic acidosis	Didanosine	Pancreatitis Peripheral neuropathy	Avoid concomitant use with Stavudine, Hydroxyurea, or Ribavirin Reduce dose when coadminstered with Tenofovir Peripheral neuropathy: avoid other neurotoxins, limit EtOH; consider treat with Gabapentin, TCAs, Lamotrigine
	Stavudine	Peripheral neuropathy Lipodystrophy (primarily fat wasting) Hyperlipidemia	Check for correct weight-based dosing; consider dose reduction or switch to another agent if symptoms Avoid concomitant use with Didanosine Peripheral neuropathy: avoid other neurotoxins, limit EtOH; consider treat with Gabapentin, TCAs, Lamotrigine
	Lamivudine	Generally well tolerated Nausea, headache Severe acute exacerbations of HBV upon drug discontinuation	Closely monitor LFTs in HIV/HBV co-infected patients if drug discontinued
	Abacavir	Black Box Warning: Hypersensitivity reaction Nausea, vomiting, diarrhea	Recommend screen for HLA-B*5701 (an MCH class I allele) to determine if patient at risk for hypersensitivity reaction; if positive, do not start Abacavir Hypersensitivity reaction should be suspected if patient presents with 2 or more of the following: fever, rash, GI symptomsa, constitutional symptomsb, respiratory symptomsc If hypersensitivity reaction suspected, stop drug immediately and do not rechallenge as fatal reactions can occur upon re-exposure (includes other products containing Abacavir)
	Tenofovir	Nausea, vomiting, diarrhea, flatulence Nephrotoxicity (eg, ↑ SCr, proteinuria, Fanconi’s syndrome) Severe acute exacerbations of HBV upon drug discontinuation	Avoid other nephrotoxic drugs Monitor SCr, UA, serum potassium and phosphorus (especially in at-risk patients) Closely monitor LFTs in HIV/HBV co-infected patients if drug discontinued
	Emtricitabine	Generally well tolerated Nausea, headache Hyperpigmentation of palms, soles Severe acute exacerbations of HBV upon drug discontinuation	Closely monitor LFTs in HIV/HBV co-infected patients if drug discontinued
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)	Nevirapine	Black Box Warning: Severe, life-threatening, and even fatal hepatotoxicity; skin reactions (including Stevens-Johnson Syndrome) Rash, ↑ LFTs Nausea, vomiting, headache	Avoid initiating in women with CD4 >250 cells/mm^3, in men with CD4 >400 cells/mm^3 Always initiate with a 2-week lead-in period with Nevirapine 200 mg once daily Monitor LFTs, skin
	Delavirdine	Rash, ↑ LFTs
	Efavirenz	CNS symptomsd (very common, >50%) Rash, ↑ LFTs False-positive cannabinoid tests ↑ lipids (including HDL)	Efavirenz should be taken on an empty stomach (avoid fatty foods); take before bedtime (or 2–3 hours before bedtime) CNS symptoms usually resolve (or diminish) after 2–4 weeks of therapy; warn patients to limit risky activities until effects are known
	Etravirine	Rash Nausea	Etravirine should be taken following a meal as fasting conditions absorption by 50% Etravirine tablets may be dispersed in glass of water if patient unable to swallow whole
Protease inhibitors (PIs)	Saquinavir	Headache, fatigue, abdominal pain	For HIV treatment, Saquinavir should only be used combined with Ritonavir (in order to attain adequate drug levels)
Note: All PIs have been associated with GI intolerance (nausea, vomiting, diarrhea),↑ LFTs, hyperglycemia, hyperlipidemia (especially hyper- triglyceridemia), and fat maldistrubution; increased bleeding episodes may be seen in patients with hemophilia	Indinavir	Hyperbilirubinemia Nephrolithiasis	Hyperbilirubinemia is usually a result of ↑ indirect (unconjugated) bilirubin; generally asymptomatic, however discontinue drug if concurrent ↑ LFTs and symptoms Patients should keep hydrated with at least 1.5–2 liters/day of fluid (noncaffeinated preferred) to decrease likelihood of nephrolithiasis
	Ritonavir	Perioral parasthesia Taste perversion Asthenia	Commonly used in low doses combined with other protease inhibitors as a pharmacokinetic enhancer (termed “boosting”)
	Nelfinavir	Diarrhea (very common, up to 50%)	Consider preemptive antidiarrheals (eg, Loperamide, Diphenoxylate/Atropine) Calcium tablets, bulk-forming agents (eg, Psyllium), and pancreatic enzymes have been used anecdotally
	Fosamprenavir	Headache Nausea, vomiting, diarrhea Rash (sulfa moiety)	Use with caution, monitor closely in patients with sulfonamide allergy
	Atazanavir	Hyperbilirubinemia Nephrolithiasis PR interval prolongation	Hyperbilirubinemia is usually a result of ↑ indirect (unconjugated) bilirubin; generally asymptomatic, however discontinue drug if concurrent ↑ LFTs and symptoms Use caution in patients with underlying cardiac conduction abnormalities or taking other medications that can prolong PR interval
	Lopinavir/Ritonavir	Perioral parasthesia, asthenia ↑ GGT	GI intolerance much more likely with once-daily dosing than twice-daily dosing
	Tipranavir	Black Box Warning: Clinical hepatitis and hepatic decompensation (including fatal reactions) Black Box Warning: Intracranial hemorrhage (both fatal and nonfatal) have been reported, however causal relationship not yet established	For HIV treatment, Tipranavir should only be used combined with Ritonavir (in order to attain adequate drug levels) Use contraindicated in patients with Child-Pugh class B or C hepatic insufficiency
		Rash (sulfa moiety)	Monitor closely for hepatotoxicity in patients co-infected with HBV and/or HCV Use with caution in patients at increased risk for bleeding
	Darunavir	Rash (sulfa moiety) Neutropenia Nasopharyngitis Headache	For HIV treatment, Darunavir should only be used combined with Ritonavir (in order to attain adequate drug levels) Use with caution, monitor closely in patients with sulfonamide allergy
Fusion inhibitors	Enfuvirtide	Injection site reactionse (very common, >90–95%) Bacterial pneumonia Hypersensitivity reaction uncommon	Patients should be counseled on sterile and administration techniques; rotate injection sites Massaging injection area may reduce pain, nodules Warm compress, analgesics, antihistamines may be used as necessary
Entry inhibitors	Maraviroc	Black Box Warning: Hepatotoxicity with allergic-type reaction (eg, pruritic rash, eosinophilia) have been reported Diarrhea, nausea, vomiting Postural hypotension, headache Fever, respiratory symptoms (eg, cough, infection)	Monitor LFTs, allergic-type reaction (allergic-type reaction may preceed hepatotoxicity)
Integrase inhibitor	Raltegravir	Diarrhea, nausea Headache ↑ Creatine kinase	Cancers commonly associated with severe immunodeficiency were reported in clinical trials, however it is unknown at this time if this is directly related to Raltegravir treatment Caution in patients already at risk for myopathy or rhabdomyolysis

Abbreviations: FDA, Food and Drug Administration;↑, increase;↓, decrease; CBC, complete blood count; EPO, erythropoietin; GCSF, filgrastim; TCA, tricyclic antidepressant; EtOH, alcoholic beverages; SCr, serum creatinine; UA, urinalysis; LFTs, liver function tests; HBV, Hepatitis B virus; HCV, Hepatitis C virus; GGT, Gamma-glutamyl transferase.

a Notes: Gastrointestinal (GI) symptoms may include nausea, vomiting, diarrhea, abdominal pain;

b Constitutional symptoms may include generalized malaise, fatigue, body aches, loss of appetite;

c Respiratory symptoms may include dyspnea, cough, pharyngitis;

d Central nervous system (CNS) symptoms may include dizziness, somnolence, insomnia, abnormal dreams (eg, nightmares, vivid dreams), confusion, abnormal thinking or difficulty concentrating, amnesia, agitation, hallucinations, euphoria;

e Injection site reactions may include pain, erythema, induration, nodules, cysts, pruritis.

Table 5 Significant drug–drug interactions that may be seen in the elderly where concomitant use is contraindicateda

Drug Class	Cardiovascular agents	Lipid lowering agents	Anti-microbials	Anti-histamines	Gastrointestinal agents	CNS agentsb	Herbals	Other
Antiretrovirals: Nonnucleoside reverse transcriptase inhibitors
Nevirapine	–	–	Rifampin	–	–	–	St. John’s Wort	–
			Rifapentine
Delavirdine	–	Lovastatin	Rifampin	Astemizole	Cisapride	Alprazolam	St. John’s Wort	Amprenavir
		Simvastatin	Rifapentine	Terfenadine	H2 blockers	Midazolam		Fosamprenavir
			Rifabutin		PPI	Triazolam		Carbamazepine
						Ergot alkaloids		Phenobarbital
								Phenytoin
Efavirenz	–	–	Rifapentine	Astemizole	Cisapride	Midazolam	St. John’s Wort	Voriconazole
				Terfenadine		Triazolam
						Ergot alkaloids
Etravirine	–	–	Rifampin	–	–	–	St. John’s Wort	Unboosted PIs
			Rifapentine					Boosted ATV, FPV, TPV
								Carbamazepine
								Phenobarbital
								Phenytoin
Antiretrovirals: Protease inhibitors
Saquinavir	–	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Fluticasone
		Simvastatin	Rifapentine	Terfenadine		Midazolam
			Rifabutinc			Triazolam
						Ergot alkaloids
Indinavir	Amiodarone	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Atazanavir
		Simvastatin	Rifapentine	Terfenadine		Midazolam
						Triazolam
						Ergot alkaloids
Ritonavir	Amiodarone	Lovastatin	Rifapentine	Astemizole	Cisapride	Pimozide	St. John’s Wort	Voriconazoled
	Bepridil	Simvastatin		Terfenadine		Midazolam
	Flecanide					Triazolam
	Propafenone					Ergot alkaloids
	Quinidine
Nelfinavir	–	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	–
		Simvastatin	Rifapentine	Terfenadine		Midazolam
						Triazolam
						Ergot alkaloids
Fosamprenavir	Bepridil	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Delavirdine
		Simvastatin	Rifapentine	Terfenadine		Midazolam		Fluticasone
						Triazolam
						Ergot alkaloids
Atazanavir	Bepridil	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Fluticasone
		Simvastatin	Rifapentine	Terfenadine	PPI	Midazolam		Indinavir
						Triazolam		Irinotecan
						Ergot alkaloids
Lopinavir/Ritonavir	Flecanide	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Fluticasone
	Propafenone	Simvastatin	Rifapentine	Terfenadine		Midazolam
						Triazolam
						Ergot alkaloids
Tipranavir/Ritonavir	Amiodarone	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	St. John’s Wort	Fluticasone
	Bepridil	Simvastatin	Rifapentine	Terfenadine		Midazolam
	Flecanide					Triazolam
	Propafenone					Ergot alkaloids
	Quinidine
Darunavir/Ritonavir	–	Lovastatin	Rifampin	Astemizole	Cisapride	Pimozide	–	Carbamazepine
		Simvastatin	Rifapentine	Terfenadine		Midazolam		Phenobarbital
						Triazolam		Phenytoin
						Ergot alkaloids		Fluticasone
Antiretrovirals: Entry inhibitor
Maraviroca,e	–	–	Rifampin	–	–	–	St. John’s Wort	–
			Rifapentine

Abbreviations: PPI, proton pump inhibitors; FDA, Food and Drug Administration; PIs, protease inhibitors; ATV, Atazanavir; FPV, Fosamprenavir; TPV, Tipranavir.

Notes: Drugs listed to the right should not be used with the corresponding antiretroviral drug listed in the left hand column;

a Adapted from publicly available resource (DHHS 2008);

b Central nervous system (CNS) agents includes neuroleptics and psychotropics; Midazolam may be used with caution for procedural sedation, otherwise extended concomitant use is contraindicated;

c Rifabutin may be used with Ritonavir-boosted Saquinavir;

d Concomitant Voriconazole is contraindicated with Ritonavir doses ≥400mg BID;

e Selzentry PI 2007.

Department of Health and Human Services: Panel on Antiretroviral Guidelines for Adults and Adolescents2008Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online] Accessed January 29, 2008 URL: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf

 Google Scholar

HammerSMSaagMSSchechterM2006Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panelJAMA2968274316905788

 PubMed Web of Science ®Google Scholar

[CDC] Centers for Disease Control and Prevention2002Guidelines for preventing opportunistic infections among HIV-infected persons – 2002: recommendations of the US Public Health Service and the Infectious Diseases Society of AmericaMMWR51152

 Google Scholar

ManfrediR2002HIV disease and advanced age: an increasing therapeutic challengeDrugs Aging196476912381235

 PubMed Web of Science ®Google Scholar

CooperDGatellJRockstrohJ2007Results of BENCHMRK-1, a phase III study evaluating the efficacy and safety of a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus [conference abstract]14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, CA, USA

 Google Scholar

IsentressPI2007Isentress™ (raltegravir) tablets [prescribing information]Merck and Co., IncWhitehouse Station, NJ, USA

 Google Scholar

LalezariJGoodrichJDeJesusE2007Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the US and Canada [conference abstract]14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, CA, USA

 Google Scholar

NelsonMFatkenheuerGKonourinaI2007Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-week results [conference abstract]14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, CA, USA

 Google Scholar

SelzentryPI2007Selzentry™ (maraviroc) tablets [prescribing information]Pfizer IncNew York, NY, USA

 Google Scholar

SteigbigelRKumarPEronJ2007Results of BENCHMRK-2, a phase III study evaluating the efficacy and safety of a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus [conference abstract]14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, CA, USA

 Google Scholar

IntelencePI2008Intelence™ (etravirine) tablets [prescribing information]Tibotec IncRaritan, NJ, USA

 Google Scholar