Epstein R et al.Awkward moments in patient-physician communication about HIV risk.Ann Int Med 1998; 128: 435.Good reference re: primary care settings from Rochester authors.

Federal HIV/ AIDS Statistics

http://www.cdc.gov/nchstp/hiv_aids/stats.htm

Newest Information on Early Intervention and Treatment Adherence

1.Chaisson, RE, Keruly, JC, Moore, RD.Association of Initial CD4 Cell Count and Viral Load With Response to Highly Active Antiretroviral TherapyJAMA 284 No. 24,December 27, 2000

http://jama.ama-assn.org/issues/v284n24/ffull/jlt1227-6.html

2. Paterson DL, Swindells, S, Mohr, J, Brester, M et al.Adherence to Protease Inhibitor Therapy and Outcomes in Patients with HIV Infection.Ann Int Med 4 July 2000 Volume 133 Number 1

http://www.annals.org/issues/v133n1/full/200007040-00004.html

HIV Treatment and Viral Load Monitoring

1.Gallant, JE.Strategies for Long-term Success in the Treatment of HIV Infection . JAMA. 2000;283:1329-1334

http://jama.ama-assn.org/issues/v283n10/full/jgh90001.html

2. Havlir DV, Marschener IC, Hirsch MS, et al. Maintenance antiretroviral therapies in HIV-infected subjects withundetectable plasma HIV RNA after triple-drug therapy. N Engl J Med

1998; 339:1261-8.

http://www.nejm.org/content/1998/0339/0018/1261.asp

3.Pialoux P, Raffi F, Brun-Vezinet F, et al. A randomized trial of three maintenance regimens given after three months ofinduction therapy with zidovudine, lamivudine, and indinavir in

previously untreated HIV-1-infected patients. N Engl J Med 1998; 339:1269-76.

See NEJM web site:http://www.nejm.org/content/1998/0339/0018/1269.asp

c.HIV Testing-United States-1996.MMWR.January 29, 1999 / 48(03);52-55

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00056332.htm

5.Hughes M et al.Monitoring plasma HIV-1 rna in addition to CD4 improves assessment of antiviral therapeutic response.Ann Int Med 1997; 126: 929.

6.O Brien W et al.Changes in plasma HIV-1 rnalevels and CD4 predict both reposnse to antiretroviral therapy and therpeutic failure.Ann Int Med 1997; 126: 939.

7.Mellors JW et al.Plasma viral load and CD4 lymphocytes as prognostic markers in HIV-1 infection.Ann Int Med 1997; 126: 946.

8.Hepatitis C co-infection is a new problem.

Recommendations for Prevention and Control of Hepatitis C Virus ...MMWR.Vol 47, No RR19;110/16/1998

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00055154.htm

The 2 references below talk about the importance of experienced providers for HIV care.

Kitahata MM, Koepsell TD, Deyo RA, et al: Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival. N Engl J Med 334:701-706, 1996.

http://www.nejm.org/content/scripts/search/keyword.asp?title=&author=kitahata

Becker, S.Resource utilization in HIV care: the case for the expert provider.

Abstract 464.

log on ICAAC 99:http://www.asmusa.org/mtgsrc/ic99main.htm

then go to:

http://asm.ctt-inc.com/itinerarybuilder/Presentation.asp?CN=9361&MID=%2522CIacwg%257E%2560%253By

Rapid HIV Testing

Impact

http://wonder.cdc.gov/wonder/prevguid/m0051718/entire.htm

Issues for Counselors

http://www.cdc.gov/nchstp/hiv_aids/pubs/rt/rapidct.htm

Sensitivity, Specificity

http://www.cdc.gov/nchstp/hiv_aids/pubs/rt/sensitivity.htm

Background on Calculating Comparisonsfor the Use of Rapid HIV Testing

http://www.cdc.gov/nchstp/hiv_aids/pubs/rt/background.htm

STD HIV Early detection screening tool

http://www.cdc.gov/nchstp/dstd/MMWRs/hiv_prevention_through_early_detection.htm

Prevention

http://www.cdc.gov/nchstp/hiv_aids/pubs/faq/faq7.htm

Publications list from above

http://www.cdc.gov/nchstp/hiv_aids/pubs/rt.htm

Attenuated HIV Infection & Vaccine Implications

Learmont, JC et al. Immunologic and Virologic Status after 14 to 18 Years of Infection with an Attenuated Strain of HIV-1 -- A Report from the Sydney Blood Bank Cohort.N Eng J Med.1999; 340: 1715-22.

http://www.nejm.org/content/1999/0340/0022/1715.asp

Editorial.Collins, KL and Nabel, GJ. Naturally Attenuated HIV -- Lessons for AIDS Vaccines and Treatment. N Eng J Med.1999; 340: 56-7.

http://www.nejm.org/content/1999/0340/0022/1756.asp

Wasting and Lipodystrophy Syndrome

Corcoran, C and Grinspoon, S. Drug Therapy: Treatments for Wasting in Patients with the Acquired Immunodeficiency Syndrome.N Eng J Med.1999; 340: 1740-50

http://www.nejm.org/content/1999/0340/0022/1740.asp

Nutrition and HIV; discussion of lipodystrophy

NuMedX

http://numedx.com

Immune Recovery and Prophylaxis for Pneumocysitis

Discontinuation of Primary Prophylaxis against Pneumocystis carinii Pneumonia in

HIV-1-Infected Adults Treated with Combination Antiretroviral Therapy

http://www.nejm.org/content/1999/0340/0017/1301.asp

Hansjakob Furrer et al

The New England Journal of Medicine -- April 29, 1999 -- Vol. 340, No. 17

Masur,, HM and Kaplan, J.(Editorial ) Does Pneumocystis carinii Prophylaxis Still Need to Be Lifelong? New England Journal of Medicine -- April 29, 1999 -- Vol. 340, No. 17

http://www.nejm.org/content/1999/0340/0017/1356.asp

Schneider et al.Discontinuation of PCP prophylaxis in patients treated with HAART.Lancet 1999; 353: 201-03.

Genotype & Phenotype Testing

Hirsch, M et al.Antiretroviral drug resistance testing in adults with HIV infection:implications for clinical management.JAMA 1998; 279:1984-1991.

http://www.ama-assn.org/special/hiv/library/readroom/jama98/jst80001.htm#tab2

Baxter JD, Mayers DL, Wentworth DN, et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. AIDS. 2000;14:F83-F92.

Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet. 1999;353:2195-2199.

Mayers D. Keynote: HIV drug resistance testing is worth the cost. Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Session MoOr31.

Cohen C, Kessler H, Hunt S, et al. Phenotypic resistance testing significantly improves response to therapy: final analysis of a randomized trial (VIRA3001). Antiviral Ther. 2000;5(suppl 3):67.

Meynard JL, Vray M, Morand-Joubert L, et al. Impact of treatment guided by phenotypic or genotypic resistance tests on the response to antiretroviral therapy: a randomized trial (NARVAL, ANRS 088). Antiviral Ther. 2000;5(suppl 3):67-68.

Viral Resistance Web Site:http://www.viral-resistance.com

HIV Sequence Data Base:http://hiv-web.lanl.gov

LabCorp of America Web Site:see links under Resistance

http://www.labcorp.com/datasets/labcorp/html/chapter/body_r.htm

http://www.hivresistance.com

HIV Clinical Resources: NYS Department of Health

A collection of guidelines and HIV information from NYS DOH AIDS Institute

http://www.hivguidelines.org/

Infection Control and Post Exposure Prophylaxis

Guidelines and Reviews of post exposure prophylaxis

·Centers for Disease Control and Prevention. Public health service guidelines for the management of health care workers exposed to HIV and recommendations for post-exposure to prophylaxis. MMWR Morb Mortal Wkly Rep. 1998;47:1-28.

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00052722.htm

·Centers for Disease Control and Prevention.Management of Possible Sexual, Injecting-Drug?Use, or Other Nonoccupational Exposure to HIV, Including Considerations Related to Antiretroviral Therapy MMWR Recommendations and Reports, Vol. 47, No. RR-17

Sep. 25, 1998. http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00054952.htm

D'Amico, R et al.Effect of zidovudine postexposure prophylaxis on the development of HIV-specific cytotoxic lymphocyte responses in HIV-exposed health care workers.Infection Control and Hospital Epidemiology.1999; 20; 428.

http://www.slackinc.com/general/iche/ichetoc.htm

Solomon, L et al.Occupational exposure and voluntary HIV testing:a survey of maryland hospitals. .Infection Control and Hospital Epidemiology.1999; 20, 430.

Only 6% of source patients refused to consent to HIV testing after HIV occupational exposure.

http://www.slackinc.com/general/iche/ichetoc.htm

Sepkowitz, KA et al. Postexposure Prophylaxis for Human Immunodeficiency Virus:

Frequency of Initiation and Completion of Newly Recommended Regimen.Infection Control and Hospital Epidemiology.1998; 19:

Only50% of HCWs given prophylaxis completed a 4 week course of PEP…

http://www.slackinc.com/general/iche/stor0798/ccsep.htm

Katz, MH and Gerberding J. The Care of Persons with Recent Sexual Exposure to HIV Annals of Internal Medicine, 15 February 1998. 128:306-312. http://www.acponline.org/journals/annals/15feb98/exposhiv.htm

Vanchieri , C. Is HIV Prophylaxis Effective for Sexual Exposures?Ann Int Med. 15 March 1998

http://www.acponline.org/journals/annals/15mar98/currhiv.htm

Occupational Exposures to Body Fluids among Medical Students:A Seven-Year Longitudinal Study. Annals of Internal Medicine, 5 January 1999. 130:45-51.

http://www.acponline.org/journals/annals/5jan99/occuexpo.htm

Lot, F et al

Probable Transmission of HIV from an Orthopedic Surgeon to a Patient in France

Annals of Internal Medicine, 5 January 1999. 130:1-6.

http://www.acponline.org/journals/annals/5jan99/orthohiv.htm

Gerberding, J Provider-to-Patient HIV Transmission: How To Keep It Exceedingly Rare

Annals of Internal Medicine, 5 January 1999. 130:64-65.

http://www.acponline.org/journals/annals/5jan99/ptophiv.htm

Emilie H.S. Osbornet al.Occupational Exposures to Body Fluids among Medical Students:A Seven-Year Longitudinal Study Annals of Internal Medicine, 5 January 1999. 130:45-51.

http://www.acponline.org/journals/annals/5jan99/occuexpo.htm

Timothy W. Schacker et al.Biological and Virologic Characteristics of Primary HIV Infection .Annals of Internal Medicine, 15 April 1998. 128:613-620.

http://www.acponline.org/journals/annals/15apr98/biohiv.htm

Evaluation of Safety Devices for Preventing Percutaneous Injuries Among Health Care Workers During Phlebotomy Procedures. . MMWR Morb Mortal Wkly Rep. 1997;46:1-25.

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00045648.htm

Evaluation of Blunt Suture Needles in Preventing Percutaneous Injuries Among Health-Care Workers During Gynecologic Surgical Procedures. . MMWR Morb Mortal Wkly Rep. 1997;46:25-28.

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00045660.htm

Gerberding JL. Management of occupational exposures to blood-borne viruses. N Engl J Med. 1995;332:444-451.

Centers for Disease Control and Prevention. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected

blood--France, United Kingdom, and United States, January 1988-August 1994. MMWR Morb Mortal Wkly Rep. 1995;44:929-933.

HIV Treatment Issues:Other Good Background References

1. Saag MS, Holodniy M, Kuritzkes DR, et al. HIV viral load markers in clinical practice: recommendations of an International AIDS Society-USA Expert Panel. Nat Med. 1996;2:625-629.

2. Embretson J, Zupancic M, Ribas JL, et al. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993;362:359-362.

3.Piatak MJ, Saag MS, Yang LC, et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993;259:1749-1754

4. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373:123-126.

5.Mellors JW, Kinsley LA, Rinaldo CRJ, et al. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med. 1995;122:573-579.

6. Mellors JW, Rinaldo CR Jr, Gupta P, et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996;272:1167-1170.

7. O'Brien WA, Hartigan PM, Martin D, Esinhart J. Changes in plasma HIV-1 RNA and CD4+ lymphocyte count relative to treatment and progression to AIDS. N Engl J Med. 1996;334:426-431.

8. Vella S. Clinical experience with saquinavir. AIDS. 1996;9:21-25.

9. Markowitz M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med.1995;333:1534-1539.

9.Bryson YJ, Pang S, Wei LS, et al. Clearance of HIV infection in a perinatally infected infant. N Engl J Med. 1995;332:833-838.

11.Hydroxyureahttp://www.retroconference.org/99/abstracts/400.htm

Sexual Ethics

1. Disclosure and HIV:about 40-50% of HIV infected men and women in one survey did not disclose HIV status to sex partners.

Kalichman SC; Nachimson D.Self-efficacy and disclosure of HIV-positive serostatus to sex partners. Health Psychol 1999 May;18(3):281-7

2. College students and disclosure of condom breakage.Among the 49 men ever reporting breakage, 15 (30.6%) had ever failed to disclose knowledge of a broken condom to a female sex partner.

Warner DL et al.Disclosure of condom breakage to sexual partners [letter]

JAMA 1997 Jul 23-30;278(4):291-2

3. 650 13-18 year olds studied in 1997, 31% have had sexual intercourse.Reviews contraceptive use and disclosure.

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00054174.htm

Viral Load Mathematics

Viral load measurements of HIV-1 RNA may range from a few hundred to >1,000,000 virions (or viral copies, or viral equivalents) per mL in plasma, a 10,000-fold range.Such large ranges are most easily expressed in logarithms (logs), or exponents.

To express a number in logarithmic or exponential form, a base is raised to the power indicated by the logarithm or exponent.Although different systems of logarithms may use different bases, the base 10 is commonly used in medicine without being explicitly specified.Thus:

Decimal NumberExponential FormLogarithm

100,000,0001088

10,000,0001077

1,000,0001066

100,0001055

10,0001044

1,0001033

1001022

101011

Each number above is a tenfold change from the next (either 0.1 or 10x), or a 1-log change.For each tenfold change, the logarithm increases or decreases by 1.(The log of 10 is 1.)A 2-log change from any number is a 100-fold change, either 1/100 or 100x.(The log of 100 is 2.)When numbers are multiplied, their logarithms are added.The sum of the individual logs of the numbers that are multiplied equals the log of their product.Likewise, when a number is divided by another, the log of the divisor is subtracted from the log of the dividend to obtain the log of the quotient.

Exponents are not necessarily whole numbers; they may be decimals or even fractions.These decimal logarithms are necessary to express numbers that are not integral powers of 10.For example, with exponents rounded to one decimal place:

Decimal NumberExponential FormLogarithm

500102.72.7

75,000104.94.9

120,000105.15.1

120102.12.1

1,500,000106.26.2

85101.91.9

850102.92.9

8500103.93.9

In the last three lines above, the decimal numbers vary by tenfold and their logarithms, or logs, vary by 1.0.A tenfold change is the equivalent of a change of 1.0 in the logarithm.This is generally referred to as a 1-log change.A 2-log change, accordingly, is a 100-fold change.

A fold change can be either an increase or a decrease—for example, a twofold increase is a doubling in value, while a twofold decrease is a halving in value.Since the log of 2 is about 0.3, if a number is multiplied by 2 (a twofold increase), its log increases by 0.3.Conversely, if a number is divided by 2 (a twofold decrease), its log decreases by 0.3:

Decimal NumberExponential FormLogarithm

8100.90.9

16101.21.2

32101.51.5

64101.81.8

Generally, in viral load measurements, the sum of laboratory and biologic variation is 0.3 to 0.5 log (2-fold to 3-fold).Therefore, only changes larger than this are regarded as significant.Most CD4 cell counts vary over a range of 10 cells/µL to >1,000 cells/µL (2 logs or 100-fold), a range not considered wide enough to require logarithms.

Bill Valenti MD

bvalenti@servtech.com

rev 3.23.00