Emtricitabine/tenofovir disoproxil fumarate one tablet daily can be considered for

F.C. for the prevention of HIV. He will need to have baseline HIV, STI, and renal

function testing as well as medication adherence and behavioral risk reduction

counseling. He will need to follow up 3 months after emtricitabine/tenofovir

disoproxil fumarate if prescribed for monitoring and repeat HIV testing.

Postexposure Prophylaxis

CASE 76-6

QUESTION 1: L.T. is a 47-year-old nurse at an HIV clinic. While drawing routine labs on a newly diagnosed

HIV+ male patient, not yet started on HAART, she accidently stuck herself with a contaminated needle. Are

interventions available to prevent L.T. from contracting HIV from the needlestick? What drugs should be

utilized, and for how long?

Postexposure prophylaxis (PEP) is the use of ARVs to prevent HIV infection in

individuals who have had an exposure to blood or body fluid either known to be

infected with HIV or potentially infected with HIV. Occupational exposures require

immediate evaluation with a first dose of ARVs offered within the first 2 hours

following exposure.

129

,

130 PEP is more effective the earlier it can be initiated, and it

should always be started within 72 hours of exposure. Percutaneous exposure poses

more of a concern than mucous membrane exposure. A needle stick with a large

hollow-bore needle is higher risk than a solid needle, a deep penetrating wound is

considered a high-risk exposure compared to a superficial injury, and a exposure to a

large volume of infectious fluid is more concerning than exposure to a low volume.

Patient-specific factors must also be considered, such as whether the HIV-positive

patient is on HAART therapy and has a suppressed viral load or whether the HIVpositive patient currently has a high viral load. Regardless of the type of exposure or

risk factors, current guidelines recommend that PEP be offered to all health care

workers with an exposure. If the source patient is known to be HIV positive or the

HIV status is not known, PEP should be continued for a total of 4 weeks, or 28 days.

If the source patient’s status is unknown but is later determined to be HIV negative,

then PEP can be discontinued prior to 28 days.

129

,

130

Three-drug PEP is recommended for all health care workers exposed or possibly

exposed to HIV. Recommended regimens include two NRTIs with either raltegravir

or dolutegravir. Alternative regimens include two NRTIs with a boosted PI.

130

In instances where the source patient is a known treatment experienced patient

with HIV, the choice of agents to use for PEP is generally dependent on the patient’s

regimen and resistant profile.

129

,

130

L.T. should start immediately a PEP regimen, preferably emtricitabine/tenofovir

disoproxil fumarate once daily with raltegravir twice daily or dolutegravir once

daily. This entire regimen should be continued for a total of 4 weeks. It would also

be a good idea to look at the specific patient from which the exposure occurred. If he

had a great deal of known antiretroviral drug resistance, then L.T. may need to be put

on different antiretrovirals according to the patient’s resistance profile. HIV antibody

testing using ELISA should be performed on L.T. at baseline exposure, 6 weeks, 12

weeks, and 6 months after exposure. She should also have baseline and follow-up

labs performed to assess antiretroviral toxicity. At a minimum, these should include a

complete blood count, renal and hepatic function tests, and fasting glucose while on

the protease inhibitor. Additional laboratory tests should be performed based on the

individual drugs chosen.

129

,

130

Additional guidelines exist for non-occupational HIV exposures and follow

similar risk and stratification treatment paradigms. In those instances where a person

seeks care within 72 hours of exposure to blood, genital secretions or other

potentially infected body fluids of persons known to be HIV-infected and the

exposure represents a substantial risk for HIV transmission then the person is started

on PEP in a similar fashion as with an occupation exposure and continued for 4

weeks with similar monitoring and HIV testing.

131

KEEPING CURRENT

The management of HIV infection continues to evolve. Additional important emerging

data are in HIV prevention and cure.

p. 1593

p. 1594

Table 76-7

Human Immunodeficiency Virus Internet Resources

Government Sites

American Foundation for AIDS Research: http://www.amfar.org

Centers for Disease Control and Prevention: http://www.cdc.gov

Consensus Panel Guidelines Online: http://www.aidsinfo.nih.gov

Government HIV Mutation Charts: http://hiv-web.lanl.gov

National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov

National Prevention Information Network: https://npin.cdc.gov/

United Nations AIDS Website: http://www.unaids.org/

University Sites

University of Stanford HIV Drug Resistance Database: http://hivdb.stanford.edu/

AIDS Treatment/Advocacy Groups

Project Inform: http://www.projectinform.org/

San Francisco AIDS Foundation: http://www.sfaf.org/index.html

Other Relevant Sites

The AIDS Map: http://www.aidsmap.com

Clinical Care Options: http://www.clinicalcareoptions.com

HIV Drug Interactions: http://www.hiv-druginteractions.org

HIV and Hepatitis: http://hivandhepatitis.com

HIV Treatment Information: http://i-base.info/

Medscape: http://www.medscape.com

Physician’s Research Network: http://www.prn.org

The Body for Clinicians: http://www.thebodypro.com

The overwhelming data presented at scientific meetings and in journals have made

staying informed about current issues and new developments a daunting task. As a

result, many clinicians, even those actively caring for patients who are HIV infected,

remain cautious and often confused regarding therapeutic options.

New technologies for the dissemination of medical information are constantly

evolving. The Internet has allowed clinicians worldwide to exchange ideas, teach

new concepts, and obtain access to limited resources. In addition, many research

centers, patient advocacy groups, and academic institutions have posted sites on the

Internet that have resulted in access to large amounts of high-quality medical

information. This new technology has also allowed, however, for the dissemination

of incomplete, misleading, or inaccurate information. Therefore, clinicians must

remain cautious and carefully evaluate the information obtained from various

websites.

When evaluating the quality of a website, clinicians should look for a few basic

standards.

Author qualifications. Is the author qualified to write the article or perform the

research? Is his or her affiliation or relevant credentials provided?

Attribution. Are references provided to confirm statements? Is all relevant

copyrighted information noted?

Currency. When was the content posted? Is the website updated regularly?

Disclosure. Who owns the website? Is there a conflict of interest between what is

being posted and any commercial interest?

Any Internet site that fails to meet these basic competencies should be viewed with

caution. In general, the most accurate and informative websites for HIV-specific

information come from academic institutions, government organizations, medical

societies, and patient advocacy groups. Table 76-7 lists high-quality websites that

provide timely and accurate information. A periodic evaluation of these sites often

provides sufficient information to stay up-to-date on current issues and controversies.

CONCLUSION

Given the significant advances in antiretroviral therapy over the past 30 years, HIV-1

infection is now a manageable chronic disease for those who have access to

antiretroviral therapies. The pharmacologic management of HIV continues to rapidly

evolve, but a basic understanding of viral pathogenesis and drug interactions

provides a framework that can be used to evaluate new information as it becomes

available. Although a cure is still out of reach, methods for preventing infection via

treatment as prevention, PrEP, PEP, and through the prevention of perinatal

transmission, have become increasingly effective as alternative strategies for curbing

the epidemic.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

p. 1594

p. 1595

Key References

Cohen MS et al. Prevention of HIV-1 infection with early antiretroviral therapy. N EnglJ Med. 2011;365:493. (12)

Gunthard HF et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults 2016

Recommendations of the International Antiviral Society–USA Panel. JAMA. 2016;316(2):191-210. (5)

INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J

Med. 2015;373:795–807. (65)

Temprano ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N

EnglJ Med. 2015;373:808–822. (66)

Wensing AM et al. 2017 Update of the drug resistance mutations in HIV-1. Top Antivir Med. 2017;24(4):132-141.

(4)

Key Websites

Centers for Disease Control and Prevention. HIV in the United States. 2015;

https://www.cdc.gov/hiv/basics/index.html. Accessed June 15, 2015. (9)

Centers for Disease Control and Prevention.

Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and

Interventions to Reduce Perinatal HIV Transmission in the United States.

https://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0/#. Accessed August 7, 2017. (121)

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in

HIV-1-infected adults and adolescents. Department of Health and Human Services.

https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed

August 7, 2017. (3)

US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States—

2014 Clinical Practice Guideline. U.S. Department of Health and Human Services and Center for Disease

Control. http://www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf. Accessed May 31, 2015. (128)

COMPLETE REFERENCES CHAPTER 76

PHARMACOTHERAPY OF HUMAN IMMUNODEFICIENCY

VIRUS INFECTION

Murphy EL et al. Viral Activation Transfusion Study Investigators. Highly active antiretroviral therapy decreases

mortality and morbidity in patients with advanced HIV disease. Ann Intern Med. 2001;3:17.

Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published November 2016. Accessed

August 7, 2017.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in

HIV-1-infected adults and adolescents. Department of Health and Human Services.

https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed

August 7, 2017.

Wensing AM et al. 2017 Update of the drug resistance mutations in HIV-1.Top Antivir Med. 2017;24(4):132-141.

Gunthard HF et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults 2016

Recommendations of the International Antiviral Society–USA Panel. JAMA. 2016;316(2):191-210.

World Health Organization. HIV/AIDS Data and Statistics. http://www.who.int/hiv/data/en/ Accessed August

07, 2017.

World Health Organization. Media Centre. The top 10 causes of death. 2014.

http://www.who.int/mediacentre/factsheets/fs310/en. Accessed June 12, 2015.

Adimora A. Sexual networks, social forces, and the HIV epidemic: written congressional testimony for the

September 16, 2008 Hearing. https://www.gpo.gov/fdsys/pkg/CHRG-110hhrg56578/pdf/CHRG110hhrg56578.pdf Accessed August 07, 2017.

Centers for Disease Control and Prevention. HIV in the United States At a Glance; 2015.

http://www.cdc.gov/hiv/basics/index.html. Accessed June 15, 2015.

Lane HC et al. HIV seroconversion and oral intercourse. Am J Public Health. 1991;81:658.

Page-Shafer K et al. Risk of HIV infection attributable to oralsex among men who have sex with men and in the

population of men who have sex with men. AIDS. 2002;16:2350.

Cohen MS et al. Prevention of HIV-1 infection with early antiretroviral therapy. N EnglJ Med. 2011;365:493.

Shaw GM et al. HIV transmission. Cold Spring Harb Perspect Med. 2012;2:a006965.

Perelson AS et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time.

Science. 1996;271:1582.

Fahey JL et al. Quantitative changes in T helper or Tsuppressor/cytotoxic lymphocyte subsets that distinguish

acquired immune deficiency syndrome from other immune subset disorders. Am J Med. 1984;76:95.

Cohen MS et al. Acute HIV-1 infection. N EnglJ Med. 2011;364:1943.

Salazar-Gonzalez JF et al. Genetic identity, biological phenotype, and evolutionary pathways of

transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med. 2009;206:1273.

Haase AT et al. Targeting early infection to prevent HIV-1 mucosal transmission. Nature. 2010;464:217.

Deng HK et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996;381:661.

Dragic T et al. HIV-1 entry into CD4

+

cells is mediated by the chemokine receptor CC-CKR-5. Nature.

1996;381:667.

Berson JF et al. A seven-transmembrane domain receptor involved in fusion and entry of T-cell-trophic human

immunodeficiency virus type 1 strains. J Virol. 1996;70:6288.

Levy J. Infection by human immunodeficiency virus—CD4 is not enough. N EnglJ Med. 1996;335:5280.

Wild C et al. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS

Res Hum Retroviruses. 1993;9:1051.

Bugelski PJ et al. HIV protease inhibitors: effects on viral maturation and physiologic function in macrophages. J

Leukoc Biol. 1994;56:374.

Kohl NE et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci

U S A. 1988;85:4686.

Fauci AS et al. Immunopathogenic mechanisms of HIV infection. Ann Intern Med. 1996;124:654.

Hellerstein M et al. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1 infected

humans. Nat Med. 1999;5:83.

Daar ES et al. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1

infection. N EnglJ Med. 1991;324:954.

Fox CH et al. Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA

[published correction appears in J Infect Dis. 1992;165:1161]. J Infect Dis. 1991;164:1051.

Panteleo G et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of

disease. Nature. 1993;362:355.

Richman DD et al. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad

Sci U S A. 2003;100:4144.

Pilcher CD et al. Acute HIV revisited: new opportunities for treatment and prevention [published correction

appears in J Clin Invest. 2006;116:3292]. J Clin Invest. 2004;113:937.

Ho DD et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373:123.

Wei X et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995;373:117.

Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.

Science. 1995;267:483.

Mellors JW et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma [published correction

appears in Science. 1997;275:14]. Science. 1996;272:1167.

O’Brien WA et al. Changes in plasma HIV-1 RNA and CD4

+

lymphocyte counts and the risk of progression to

AIDS. Veterans Affairs Cooperative Study Group on AIDS. N EnglJ Med. 1996;334:426.

Mellors JW et al. Plasma viral load and CD4

+

lymphocytes as prognostic markers of HIV-1 infection. Ann Intern

Med. 1997;126:946

Pantaleo G et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N

EnglJ Med. 1995;332:209.

O’Brien TR et al. Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia

cohort study. JAMA. 1996;276:105.

Sepkowitz KA. Effect of HAART on natural history of AIDS-related opportunistic disorders. Lancet.

1998;351:228.

Yarchoan R, Broder S. Development of antiretroviral therapy for the acquired immunodeficiency syndrome and

related disorder: a progress report. N EnglJ Med. 1987;316:557.

Merluzzi VJ et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor [published

correction appears in Science. 1991;251:362]. Science. 1990;250:1411.

Deeks SG et al. HIV-1 protease inhibitors: a review for clinicians. JAMA. 1997;277:145.

Acosta E et al. Pharmacodynamics of human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis.

2000;30(Suppl 2):S151.

Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65:1747.

Westby M, van der Ryst E. CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. Antivir

Chem Chemother. 2005;16:339.

Adams JL et al. Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012;7:390.

Larson KB. Pharmacokinetic Enhancers in HIV Therapeutics. Clin Pharmacokinet. 2014;53:865.

Maldarelli F. Targeting viral reservoirs: ability of antiretroviral therapy to stop viral replication. Curr Opin HIV

AIDS. 2011;6:49.

Perelson AS et al. Decay characteristic of HIV-1-infected compartments during combination therapy. Nature.

1997;387:188.

Finzi D et al. Latent infection of CD4

+ T cells provides a mechanism for lifelong persistence of HIV-1, even in

patients on effective combination therapy. Nat Med. 1999;5:512.

Zhang L et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N

EnglJ Med. 1999;340:1605.

Pomerantz RJ. Residual HIV-1 disease in the era of highly active antiretroviral therapy. N Engl J Med.

1999;340:1672.

Branson BM et al. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014.

http://stacks.cdc.gov/view/cdc/23447. Accessed June 13, 2015.

Abbott Laboratories. Summary of Safety and Effectiveness Architect HIV Ag/Ab Combo Reagent Kit.

https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProdu

Accessed June 13, 2015.

Bio-Rad Laboratories. Summary of Safety and Effectiveness GS HIV Combo Ag/Ab EIA.

https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAWorld Health Organization (WHO). Laboratory Guidelines for enumerating CD4 T Lymphocytes in the context

of HIV/AIDS; 2007.

http://www.who.int/hiv/amds/LaboratoryGuideEnumeratingCD4TLymphocytes.pdf. Accessed June 13,

2015.

Peter JB, Sevall JS. Molecular-based methods for quantifying HIV viral load. AIDS Patient Care STDS.

2004;18:75.

Lafeuillade A et al. Human immunodeficiency virus type 1 kinetics in lymph nodes compared with plasma. J

Infect Dis. 1996;174:404.

Harris M et al. Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus

infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States. J Infect Dis.

1997;176:1388.

Brichacek B et al. Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge

with pneumococcal vaccine. J Infect Dis. 1996;174:1191.

Frentz D et al. Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the World.

AIDS Rev. 2012;14:17.

US Department of Health and Human Services. Statement by the HHS Panel on Antiretroviral Guidelines for

Adults and Adolescents Regarding Results from the START and TEMPRANO Trials, 2015.

https://aidsinfo.nih.gov/news/1592/statement-from-adult-arv-guideline-panelstart-and-tempranotrials. Accessed September 09, 2015.

INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N EnglJ

Med. 2015;373:795–807.

Temprano ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N

EnglJ Med. 2015;373:808–822.

Gras L et al. CD4 cell counts of 800 cells/mm

3 or greater after 7 years of highly active antiretroviral therapy are

feasible in most patients starting with 350 cell/mm3 or greater. J Acquir Immune Defic Syndr. 2007;45(2):183–

192.

Kaufmann GR et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500

cells/microL in HIV type-1 infected individuals receiving potent antiretroviral therapy. Clin Infect Dis.

2005;41:361.

Moore RD, Keruly JC. CD4

+

cell count 6 years after commencement of highly active antiretroviral therapy in

persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441.

Calvo M et al. Update on metabolic issues in HIV patient. Curr Opin HIV AIDS. 2014;9:332.

Dube MP et al. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus

(HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV medicine association of the

Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Disease.

2003;37:613.

Dube MP et al. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to

nelfinavir or efavirenz plus dual nucleosides. AIDS. 2005;19:1807.

Friis-Moller N et al. Combination antiretroviral therapy and the risk of myocardial infarction [published correction

appears in N EnglJ Med. 2004;350:955]. N EnglJ Med. 2003;349:1993.

Henry K et al. Severe premature coronary artery disease with protease inhibitors. Lancet. 1998;351:1328.

Holmberg SD et al. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet.

2002;360:1747.

Iloeje UH et al. Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients.

HIV Med. 2005;6:37.

Mary-Krause M et al. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIVinfected men. AIDS. 2003;17:2479.

The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med.

2007;356:1723.

Cianflone K et al. Protease inhibitor effects on triglyceride synthesis and adipokine secretion in human omental

and subcutaneous adipose tissue. Antivir Ther. 2006;11:681.

100.

101.

102.

103.

104.

105.

Lenhard JM et al. HIV protease inhibitors block adipogenesis and increase lipolysis in vitro. Antiviral Res.

2000;47:121.

Mallon PW. Pathogenesis of lipodystrophy and lipid abnormalities in patients taking antiretroviral therapy. AIDS

Rev. 2007;9:3.

Martinez E et al. Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as

measured by fat mass ratio. HIV Med. 2015;16:370.

Hadigan C et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with HIV and

lipodystrophy. Clin Infect Dis. 2001;32:130.

Currier J. Management of metabolic complications of therapy. AIDS. 2002;16(Suppl 4):S171.

Distler O et al. Hyperlipidemia and inhibitors of HIV protease. Curr Opin Clin Nutr Metab Care. 2001;4:99.

van Leth F et al. Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive

patients infected with HIV-1. PLoS Med. 2004;1:e19.

Keiser PH et al. Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens

improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment. BMC Infect Dis.

2005;5:2.

Negredo F et al. Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine

or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression. Clin

Infect Dis. 2002;34:504.

Boyd MA et al. Changes in body composition and mitochondrial nucleic acid content in patients switched from

failed nucleoside analogue therapy to ritonavir-boosted indinavir and efavirenz [published correction appears in J

Infect Dis. 2006;194:870]. J Infect Dis. 2006;194:642.

Carr A et al. HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, openlabel, multicentre study. AIDS. 2001;15:1811.

Hatano H et al. Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy.

AIDS. 2000;14:1935.

Moyle GJ et al. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine

analogue in persons with lipoatrophy. AIDS. 2006;20:1043.

Saag MS et al. Switching antiretroviral drugs for treatment of metabolic complications in HIV-1 infection:

summary of selected trials. Top HIV Med. 2002;10:47.

Falutz J et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human

immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter,

double-blind placebo controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab.

2010;95:4291.

Moyle G. Plastic surgical approaches for HIV-associated lipoatrophy. Curr HIV/AIDS Rep. 2005;2:127.

Guaraldi G et al. Comparison of three different interventions for the correction of HIV-associated facial

lipoatrophy: a prospective study. Antiviral Ther. 2005;10:753.

Wang H et al. The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in

antiretroviral regimens for HIV-1 therapy Meta-analysis. Medicine. 2016; 95:41(e5146).

Ortego C et al. Adherence to Highly Active Antiretroviral Therapy (HAART): a meta-analysis. AIDS Behav.

2011;15:1381.

Stone VE. Strategies for optimizing adherence to highly active antiretroviral therapy: lessons from research and

clinical practice. Clin Infect Dis. 2001;33:865.

Palella FJ, Jr et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease

in the HIV Outpatient Study. J Acquir Immune Defic Syndr. 2006;43:27.

Powderly WG et al. Predictors of optimal virological response to potent antiretroviral therapy. AIDS.

1999;13:1873.

Jacobson MA et al. Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy. Lancet.

1997;349:1443.

Kempen JH et al. Risk of immune recovery uveitis inpatients with AIDS and cytomegalovirus retinitis.

Ophthalmology. 2006;113:684.

Race EM et al. Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients

with advanced HIV-1 disease. Lancet. 1998;351:252.

Lederman MM et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy

consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect

Dis. 1998;178:70.

106.

107.

108.

109.

110.

111.

112.

113.

114.

115.

116.

117.

118.

119.

120.

121.

122.

123.

124.

125.

126.

127.

128.

129.

130.

131.

Pakker NG et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1

infection: a composite of redistribution and proliferation. Nat Med. 1998;4:208.

Roederer M. Getting to the HAART of T-cell dynamics. Nat Med. 1998;4:145.

Lee PK et al. HIV-1 viral load blips are of limited clinicalsignificance. J Antimicrob Chemother. 2006;57:803.

Sungkanuparph S et al. Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside

reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are

equivalent in incidence and prognosis. Clin Infect Dis. 2005;41:1326.

Marias J et al. Transient rebounds of HIV plasma viremia are associated with the emergence of drug resistance

mutations in patients on highly active antiretroviral therapy. J Infect. 2005;51:195.

Boden D et al. HIV-1 drug resistance in newly infected individuals. JAMA. 1999;282:1135.

Hecht FM et al. Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease

inhibitors. N EnglJ Med. 1998;339:307.

Yerly S et al. Transmission of antiretroviral-drug-resistant HIV-1 variants. Lancet. 1999;354:729.

Tang MW, Shafer RW. HIV-1 antiretroviral resistance: scientific principles and clinical applications. Drugs.

2012;72(9):e1–e25.

Deeks SG et al. Persistence of drug-resistant HIV-1 after a structured treatment interruption and its impact on

treatment response. AIDS. 2003;17:361.

Leigh Brown AJ et al. Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence

of resistance in the antiretroviral-treated population. J Infect Dis. 2003;187:683.

Acosta EP et al. Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res Hum

Retroviruses. 2002;18:825.

Pretorius E et al. The role of therapeutic drug monitoring in the management of patients with human

immunodeficiency virus infection. Ther Drug Monit. 2011;33(3):265–274.

http://www.ncbi.nlm.nih.gov/pubmed/21566505.

Molto J et al. Variability in non-nucleoside reverse transcriptase and protease inhibitors concentrations among

HIV-infected adults in routine clinical practice. Br J Clin Pharmacol. 2007;63(6):715–721.

Nettles RE et al. Marked intraindividual variability in antiretroviral concentration may limit the utility of

therapeutic drug monitoring [published correction appears in Clin Infect Dis. 2006;43:672]. Clin Infect Dis.

2006;42:1189.