HIV IN PRIMARY
CARE
Miriam Rabkin,
M.D.
There are now close to a million people in the United States infected
with the human immunodeficiency virus (HIV), and the primary care of these
patients is provided by generalists as well as subspecialists. Internists play a
vital role, as well, in testing, counseling and educating both HIV-negative and
HIV-positive patients. While the previous edition of this chapter attempted to
provide a general overview of HIV care, it has become increasingly clear that
antiretroviral therapy should only be prescribed by those expert in its use.[i],[ii]
This chapter will focus on HIV testing, harm-reduction counseling, primary HIV
infection and post-exposure prophylaxis. More detailed discussions can be found
in the resources, references and websites listed at the end of the chapter.
Testing at-risk people for HIV is essential in order to provide adequate health care and counseling. With no vaccine expected in the near future, behavior modification and treatment of infected patients are the only possible ways to stem the epidemic. Risk-reduction behavior - such as abstinence, condom use and the use of clean needles - clearly reduces HIV transmission. The use of highly active antiretroviral medications makes patients live longer and feel better – it may also make them less infectious. Although testing is increasingly frequent, more than 20 percent of the one million HIV-infected people in the U.S. are thought to be unaware of their serostatus,[iii] and there are an estimated 40,000 new infections a year in this country.[iv] This is in spite of the fact that 23.2 percent of Americans were voluntarily tested for HIV in 1996 (the most recent year for which data are available).[v] While HIV testing can be emotionally difficult for doctor and patient, identifying HIV-infected people has enormous potential benefit both for the individual and for the community.
“High
risk” patients are those who belong to populations known to have a high
prevalence of HIV infection: sexual partners of patients with HIV, injection
drug users, people with multiple sexual partners, men who have sex with men,
people with other sexually transmitted diseases and children of HIV-positive
mothers. Blood products have been screened for HIV-1 since 1985 and for HIV-2
since 1992; the risk of infection from blood transfusion subsequent to 1985 is
extremely low (estimated at 1/100,000 transfused units).[vi]
Of note, screening of blood products in the Dominican Republic is not
standardized and the risk of a transfusion in the DR is currently unknown.[vii]
While
complete seroprevalence data are lacking, the rates of HIV in New York City are
clearly high. The NYC Department of Health reported 4,685 cases of AIDS in 1998
(case rate 64:100,000);[viii] Federal data through
June 1999 suggest an even higher NYC case rate of 75:100,000.[ix]
Some surveys suggest that 15 percent of patients in NYC emergency rooms are HIV-infected.[x],[xi]
Forty percent of injection drug users in New York are HIV-infected, as are 3.3
percent of pregnant women delivering at our neighboring Harlem Hospital.[xii]
We practice in an endemic area.
There
is a growing sense that the threshold for HIV testing has been unreasonably
high. In addition, generalists fail to recognize common HIV-associated
conditions – such as the pathognomonic oral hairy leukoplakia – when
presented with standardized patients,[xiii] and may not realize that
others – such as seborrheic dermatitis, psoriasis and herpes zoster may be
indications for HIV testing. Primary care providers may also fail to identify
risk behaviors.[xiv]
Several recent articles have urged primary care providers to “Think HIV”[xv]
and to abandon what the authors feel is a passive approach to HIV testing.[xvi]
Table 1 summarizes testing recommendations:
TABLE 1:
Which adult New Yorkers should be tested for HIV?*
Condition/risk
group:
|
HIV testing
strongly recommended |
Consider HIV
testing |
|
Injection drug users |
4 |
|
|
Men who have sex with men |
4 |
|
Sexual partners of HIV+ persons
|
4 |
|
Persons with other STDs
|
4 |
|
Pregnant women (and those planning
pregnancies)
|
4 |
|
Recipients of transfusion or blood
products prior to 1985
|
4 |
|
Health care workers with occupational
exposure to HIV
|
4 |
|
Heterosexuals with multiple sexual
partners
|
4 |
|
Commercial sex workers
|
4 |
|
Persons who exchange sex for drugs
|
4 |
|
Persons with oral hairy leukoplakia
|
4 |
|
Persons who use cocaine
|
|
4 |
Person with alcohol dependence
|
|
4 |
Persons with herpes zoster
|
|
4 |
Persons with seborrheic dermatitis
|
|
4 |
Persons with psoriasis
|
|
4 |
Young adults with community-acquired
pneumonia
|
|
4 |
Persons with pneumococcal bacteremia
|
|
4 |
Women with CIN or cervical cancer
|
|
4 |
Women with recurrent vaginal
candidiasis
|
|
4 |
Adults with unexplained weight loss
|
|
4 |
Recipients of transfusions in the
Dominican Republic
|
|
4 |
* adapted from sources 15,16,[xvii],[xviii]. This is not an all-inclusive list.
HIV
testing involves important public health and privacy issues which neither
patient nor provider should take lightly. Counseling (pre-test and post-test) is
mandated by law in the state of New York,[xix]
and the test may not be performed on an adult without written informed consent.
Providers should document that they provided pre-test and post-test counseling.
Table 2 summarizes recommendations for counseling.
Physicians
and patients should be aware of the difference between anonymous and
confidential testing. In anonymous
testing, samples are given an identifying code and the test center cannot
possibly connect the result with a name. The advantage of this method is that it
ensures patient privacy. The disadvantage is that it cannot be used to guide
therapy; a treating physician must document HIV test results in the medical
record. In confidential testing,
privacy is a goal that is not always attainable. Test results are available to
anyone with access to the medical chart, and HIV is a reportable condition in
New York City. Contact tracing and partner notification is also a standard of
care – and required by law. Anonymous testing is not available through New
York Presbyterian Hospital, but there are several centers in the city which
provide this service. Patients can call the NYC AIDS hotline at (800) 825-5548,
the New York State AIDS Information Service (800) 541-2437, Planned Parenthood
274-7200, the Geffen Center 367-1100, or GMHC 807-6655 to ask about sites near
them. It is important to establish that patients actually received the results
of their HIV tests; 10 to 15 percent of patients tested do not return for
results.[xx]
TABLE 2:
Guide to HIV pre-test and post-test counseling*
|
HIV pre-test
counseling: |
|
Discuss with patient: ü Prior history of HIV testing and counseling ü The nature of AIDS and HIV-related illness ü The benefits of early diagnosis and medical intervention ü HIV transmission and risk-reduction behaviors ü Possible discrimination resulting from the disclosure of HIV test results and the legal protections against discrimination ü Anonymous and confidential testing options ü The patient’s responsibility for partner notification ü The availability of medical, psychological and social work support. |
|
With pregnant women, also explain: ü The benefits of early diagnosis for preventing perinatal transmission and for treatment of the newborn ü That testing of the newborn will be conducted even if the mother chooses not to be tested herself (there is universal testing of neonates in NY) ü The meaning of the test for both mother and newborn |
|
The patient must be able to provide written
informed consent. If the patient does not have decisional capacity,
testing should be deferred. |
|
HIV post-test
counseling: |
|
For patients with negative test results: ü Discuss the meaning of the test result ü Discuss the possibility of exposure during the past 6 months and the need to consider retesting ü Emphasize that a negative test does not imply immunity to future infection ü Reinforce personal risk reduction strategies |
|
For patients with positive test results: ü Discuss the meaning of the test result ü Discuss the availability of medical care; provide appropriate referrals ü Encourage partner notification; discuss options ü Encourage referral of partner and children for HIV testing ü
Provide counseling re: behavior modification/risk reduction
strategies |
* New York State Department of
Health AIDS Institute Publication 0285.
Telling patients that they have a potentially fatal disease is one of the hardest things a physician must do. Counseling a patient whose HIV test is positive is a complex task, and one that may take several sessions. While there is no “right way” to do this, the CDC and the NY State Department of Health have published guidelines for HIV counseling. In addition to conveying the basic information about a patient’s HIV status, there are several topics that must be covered in post-test counseling:
(a) Behavior modification: Whether the test is negative or positive, patients should be counseled about behaviors that spread HIV. It is important to be specific when discussing sexual practices, injection drug use and behavior modification, even with patients who have been tested and counseled before. Patients should understand that HIV has been isolated from blood, semen, and vaginal secretions, as well as breast milk, pre-ejaculate and saliva. The best way to avoid contracting the disease or giving it to others is to avoid sharing body fluids with others – i.e. to abstain from penetrative sexual intercourse, exchange of secretions or needle-sharing. In lieu of this, harm-reduction strategies (see below) can effectively reduce the risk of viral transmission.
(b) Contact tracing: By law, a patient who is HIV-positive is required to inform sexual and needle-sharing partners of that fact. In practice, leaving notification up to patients is ineffective.[xxi] Other options include notifying partners yourself, or utilizing the NYC Contact Notification Assistance Project (212) 693-1419, which provides anonymous partner notification. New York State law explicitly permits a physician to violate patient confidentiality and inform patients’ partners of their exposure.[xxii] Initial steps, however, should include encouraging patients to tell their partners and offering any assistance they require. If patients refuse to cooperate, providers are in a very difficult situation. Informing their partners (if they could be found) could help stop the spread of a deadly disease and allow them to be treated if infected; it will also likely destroy the patient-physician relationship. While partner notification is the responsibility of the primary care provider, as a rule this is not a situation that should be handled by housestaff alone.
(c) Pregnancy: It is vital that your patients understand that a pregnant woman infected with HIV can pass the virus on to her fetus. Although anti-retroviral therapy in combination with Caesarian section can dramatically reduce the risk of vertical transmission,[xxiii] it does not eliminate it, and many women decide not to have children under these circumstances. HIV can be transmitted by breast milk, and HIV-infected mothers should be advised not to breast feed their children.[xxiv]
Recommendations about risk-reduction education and counseling are bounded
by two facts: it is clear that behavior modification can reduce the risk of HIV
infection, but it is not clear that counseling can dependably cause behavior
modification. Studies of specific counseling interventions and meta-analyses of
these studies[xxv],[xxvi],[xxvii]
show mixed results. Characteristics of successful counseling programs include
culturally sensitive and patient-specific counseling, repeated and consistent
counseling over time, and promotion of patient self-efficacy.
As noted in Chapter 20, a careful history is the first step in
risk-reduction counseling. Not only is it not helpful to tell a lesbian patient
to use condoms or to assume that an elderly patient is abstinent, but such
missteps will close further avenues of discussion between patient and provider.
A complete sexual history should always be taken, and patient should be asked
directly about high-risk behavior. In a respectful and non-judgmental manner,
providers should ask about frequency of sexual activity, number and gender of
partners, type of penetrative sexual activity and use or non-use of condoms.
Patients should also be asked if they are current or former injection drug
users.
A “single dose” of counseling is unlikely to effect long-lasting
behavior change. Providers should routinely and repeatedly discuss safer sex
with sexually active patients. The message should be clear, non-judgmental,
patient-specific, explicit and upbeat. The only ways to eliminate the risk of
HIV infection are to be abstinent or to have monogamous sex with an HIV-negative
partner, and all counseling should include this information. Patients who choose
to be sexually active should know that there are specific acts which are highly
risky – receptive anal intercourse with an HIV-infected partner being the most
dangerous. While exact data are elusive, insertive anal intercourse, “rough
sex” (i.e. sex in which mucosa are torn), and sex while genital ulceration is
present are also clearly high-risk. Receptive vaginal intercourse appears to be
more dangerous than insertive vaginal intercourse; it is also possible (although
much less likely) to acquire HIV through oral sex.[xxviii]
There are no reported cases of HIV-transmission via “deep” kissing, although
this is theoretically possible if one of the partners is bleeding. Prompt
treatment of other sexually transmitted diseases is essential, since these are
biological “co-factors,” which increase the risk of HIV transmission.
Sexually active patients should know that correct and consistent use of
barrier protection can dramatically reduce the risk of HIV infection.[xxix],[xxx],[xxxi]
Latex condoms (male or female), latex dental dams and non-porous (non-microwaveable)
plastic wrap are all effective barriers. In order to use a condom correctly, a
specific sequence of events must occur: recognition that sexual activity is
going to occur, access to a condom, negotiation of condom use with one’s
partner, and technical efficacy (removing the condom from its package, putting
it on correctly, using it during intercourse and removing it correctly). Only
water-based lubricants should be used with latex condoms; oil-based lubricants
can weaken the latex. Medicaid will pay for condoms with a prescription.
Users
of injection drugs should be referred to detoxification and rehabilitation
programs and encouraged to stop. As long as a patient is using, s/he should use
clean needles or clean needles and “works” in bleach. Specific guidelines
are beyond the scope of this chapter, but questions can be referred to the
social workers and peer educators in the Harkness 6 Infectious Disease clinic
(305-3174).
Primary HIV infection (P-HIV) also called the “acute retroviral
syndrome,” is the constellation of symptoms and signs that occurs in most
patients as they acquire HIV. It is critically important for generalists in
high-prevalence areas to be able to identify this syndrome for three reasons:
symptomatic patients will present to their primary care providers, patients with
primary HIV are extremely infectious, and early treatment may alter the course
of HIV disease.
There are at least 40,000 new cases of HIV in the United States each
year, half of which occur in people under 30 years of age. Both prospective and
retrospective studies suggest that two-thirds of patients are symptomatic at the
time of seroconversion and that most seek medical attention.[xxxii]
Symptomatic seroconversion has been documented in all risk categories, but
primary HIV infection is rarely suspected, even among high-risk patients.[xxxiii],[xxxiv]
While there is a broad spectrum of severity, the classic presentation is an
acute-onset self-limited “flu-like” illness that occurs two to six weeks
after exposure and resolves after one to two weeks. Symptoms are felt to
correlate to an initial burst of viremia and the associated immune response.
Clinical features are listed in Table 3, and are disappointingly nonspecific.
TABLE 3: Clinical features of primary HIV infection
Characteristic |
Percent 31,[xxxv] |
|
Fever |
96 % |
|
Fatigue |
92 % |
|
Myalgia/arthralgia |
72 % |
|
Adenopathy |
64 % |
|
Pharyngitis |
64 % |
|
Diarrhea |
46 % |
|
Headache |
44 % |
|
Rash |
40 % |
|
Weight loss |
36 % |
|
Nausea/ vomiting |
32 % |
|
Mucocutaneous ulcerations |
20 % |
|
Thrush |
12 % |
|
Thrombocytopenia |
45 % |
|
Leukopenia |
40 % |
|
Elevated LFTs |
21 % |
Because the signs and symptoms of the acute retroviral syndrome are
nonspecific, patients are often thought to have other viral infections,
including mononucleosis, influenza or viral hepatitis.[xxxvi]
A morbilloform or maculopapular rash on the trunk, arms or face is highly
suggestive in the right context.[xxxvii]
A high index of suspicion and a careful risk history are essential; patients
with no exposure to HIV in the past two months do not have primary HIV
infection.
Diagnosis of primary HIV is complicated by the fact that patients will
not yet have antibodies to HIV; standard ELISA and Western Blot tests may be
negative for the first three to six weeks after symptoms occur.[xxxviii]
If P-HIV is suspected, antigen testing
(i.e. RNA viral load testing) should be performed; this should be done with
caution as false-positive testing has been reported.[xxxix]
We recommend subspecialty consultation with the Infectious Diseases service for
patients suspected of having primary HIV infection. If you are considering the
diagnosis of primary HIV, the patient should be aware that s/he is likely extremely
infectious. Viral load during the acute retroviral syndrome can be “off the
chart,” and patients should use latex barrier protection or abstain from
penetrative sexual intercourse while symptomatic.
Primary
care providers in HIV-endemic areas should be familiar with indications for
post-exposure prophylaxis (PEP).[xl]
There are excellent websites[xli]
dedicated to this topic, and a 24-hour CDC hotline for physicians (888)
HIV-4911. One New York City program that provides free PEP has a 24-hour hotline
for patients (212) 358-2400. In brief, there are four circumstances in which PEP
is usually considered: occupational percutaneous exposure, rape, consensual
sexual exposure and exposure through injection drug use/needle sharing. There
are limited data with which to make decisions about the last three situations,
but PEP guidelines have been developed via expert consensus. It is important to
remember that there are not enough data to be dogmatic about PEP, and that in
all four scenarios, there are concerns other than HIV infection, including
hepatitis and pregnancy.
(a)
Occupational
percutaneous exposure:
There is a single case-control study of post-exposure prophylaxis among health
care workers exposed via needlestick or laboratory injury.[xlii]
The authors reviewed 33 cases and 665 controls, looking at risk factors for
seroconversion and efficacy of zidovudine (AZT) monotherapy. The average risk of
seroconversion after injury with an HIV-infected needle is about 1 in 300 (0.3
percent). The study found four independent risk factors for seroconversion: deep
injury, injury with a device visibly contaminated with the patient’s blood,
procedures involving a needle placed in the source patient’s vein or artery
and terminal illness in the source patient. An injury with any one of these
characteristics is considered to be high risk. The authors also found that the
adjusted odds ratio of seroconversion after PEP was 0.19 – i.e. that the use
of zidovudine monotherapy after occupational exposure reduced the risk of HIV
infection by 80 percent. Based on these data, the recommendations for PEP in
this setting are outlined in Table 4. Of note, the CDC suggest using four weeks
of combination antiretroviral therapy (zidovudine + epivir) instead of AZT
monotherapy. In specific very high risk situations, or ones in which the source
patient is already on antiretroviral therapy, protease inhibitors or other
nucleoside analogues are recommended. Questions about PEP can be referred to the
Infectious Diseases service; speed is essential as there are theoretical reasons
to believe that there is a “window of opportunity” for effective PEP.
Ideally, persons will take PEP within hours of occupational exposure – the
medications are available from Employee Health, the Chief Residents’ office
and the Emergency Department.
TABLE
4: Post-exposure prophylaxis for percutaneous
injuries
|
Source status |
Class IAsymptomatic; known low titer |
Class 2AIDS; symptomatic infection |
Class 3Pre-terminal AIDS; acute seroconversion; known high titer |
Exposure levelI – superficial injury |
Offer |
Recommend |
Strongly encourage |
|
II – visibly bloody device; device used in artery or
vein |
Recommend |
Recommend |
Strongly encourage |
|
III – deep/ IM injury; actual injection |
Strongly encourage |
Strongly encourage |
Strongly encourage |
(b)
Injection
drug use:
There are no trials of PEP in the context of needle-sharing, although the
pathophysiology of infection is presumably the same as that of percutaneous
exposure. It is clear that sharing needles with an HIV-infected person is one of
the highest risk behaviors there is. The probability of HIV infection in this
setting is estimated to be 0.67 – 1.00, and it is likely that PEP would
significantly reduce this risk. However, there are no
recommendations to provide PEP in the context of ongoing behavior and the
subject is an extremely controversial one.[xliii]
In addition, some experts feel that offering PEP to injection drug users sends a
mixed message and may promote IDU itself. There are no Federal guidelines; the
UCSF PEP program recommends PEP in this context only if the needle-sharing was
an isolated event and the patient intends to abstain from drug use or to use
clean needles in the future (see Table 5).
(c)
Sexual
assault: There
are scarce data on the risk of HIV-transmission after a single sexual exposure,
and no human studies of PEP in this context. In animal studies, PEP can prevent
SIV (simian immunodeficiency virus) infection in macaques after mucosal
exposure. If the source is HIV-infected, specific sexual acts are riskier than
others: receptive anal intercourse > insertive anal intercourse >
receptive vaginal intercourse > insertive vaginal intercourse >>>
oral sex. Most guidelines recommend offering PEP to survivors of rape.[xliv]
(d)
Consensual
sexual exposure:
As noted, there are no experimental data regarding PEP and sexual exposure to
HIV. As with needle sharing, there are those who worry that providing PEP in
this context will create a “mixed message,” that high-risk sexual behavior
is permissible, or that it will even promote risky sexual behaviors. This
concern is entirely theoretical, and it should be noted that the availability of
the “morning after” pill, an analogous intervention, does not seem to
increase risk behavior with regards to pregnancy. In certain communities, such
as San Francisco, provision of PEP to patients after (and sometimes even before)
high-risk sexual behavior is the standard of care.[xlv]
If the exposure is an isolated event, it may be worth considering PEP. If the
risk behavior is ongoing, however, PEP is contraindicated.
TABLE 5: UCSF Guidelines for the use of PEP
|
Consider
PEP if conditions 1-5 are met: 1)
High risk exposure (in descending order of risk) a.
unprotected
receptive anal intercourse b.
sharing
needles or drug paraphernalia c.
unprotected
receptive vaginal intercourse d.
unprotected
insertive vaginal intercourse e.
unprotected
insertive anal intercourse f.
unprotected
receptive fellatio with ejaculation
2)
Partner is known to be HIV-infected, or in an HIV risk group, or
patient was raped 3)
Exposure is an isolated event (i.e. broken condom) or patient intends
to avoid future exposure through abstinence, safer sex or clean needles 4)
Patient presents for care within 72 hours of exposure 5)
Patient desires treatment and agrees to adhere to the treatment
regimen |
We thank Dr. Peter Gordon for his helpful comments
and suggestions.
While
there are many useful textbooks of HIV medicine, the field is a rapidly-changing
one and texts may be out of date by the time they are published. The websites
listed here have more up-to-date information, but may not be peer-reviewed:
caveat emptor.
Textbook:
Sande, Volberding eds. The Medical Management of AIDS, sixth edition. W.B. Saunders, Philadelphia 1999.
Websites:
http://
2)
www.hivatis.org.
6)
www.aidsnyc.org/network/access/index.html
[i] Donohoe MT. Comparing generalist and specialty care: discrepancies, deficiencies and excesses. Arch Intern Med 1998;158:1596-1608.
[ii] The Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services/Henry J. Kaiser Family Foundation, January 2000. This entire document is available at www.hivatis.org.
[iii] Sweeny PA, Fleming PL, Karon JM et al. Minimum estimate of the number of living HIV infected persons confidentially tested in the United States. In: Program and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, D.C: American Society for Microbiology, 1997;245:abstract.
[iv] Rosenberg PS. Scope of the AIDS epidemic in the United States. Science 1995;270:1372-75.
[v] Holtzman DBS, McQueen DV. Trends in HIV testing among US adults, 1993 to 1996. In: Program and abstracts of the 12th World AIDS Conference 1998. Abstract 43127.
[vi] Lackritz E, Satten G, Aberle-Grasser J et al. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995;333:1721-25.
[vii] Personal communication: Rafael Lantigua, M.D.
[viii] Lowe C, ed. New York City Department of Health. Summary of reportable diseases and conditions 1997-98. City Health Information 1999;18:3:1-16.
[ix] Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 1999;11: 6-8.
[x] Schoenbaum EE, Webber MP. The underrecognition of HIV infection in women in an inner-city emergency room. Am J Public Health 1993;83:363-68.
[xi] Alpert PL, Shuter J, DeShaw MG et al. Factors associated with unrecognized HIV-1 infection in an inner-city emergency department. Ann Emerg Med 1996;28:159-64.
[xii] Nicholas SW, Bateman DA, Ng SK et al. Maternal-newborn human immunodeficiency virus infection in Harlem. Arch Pediatr Adolesc Med 1994;148:813-19.
[xiii] Paauw D, Wenrich M, Curtis J et al. Ability of primary care physicians to recognize physical findings associated with HIV infection. JAMA 1995;274:1380-82.
[xiv] Wenrich MD. Curtis JR, Carline JD et al. HIV risk screening in the primary care setting: assessment of physicians’ skills. J Gen Intern Med 1997;12:107-113.
[xv] Laurence J. Think HIV. AIDS Reader 2000;10:68-75.
[xvi] Freedberg KA, Samet JH. Think HIV: why physicians should lower their threshold for HIV testing. Arch Intern Med 1999;159:1994-2000.
[xvii] U.S Preventive Services Task Force. Guide to Clinical Preventive Services. Williams and Wilkins, Baltimore, Md. 1996.
[xviii] Sox HC Jr. Preventive health services in adults. N Engl J Med 1994;330:1589-95.
[xix] Article 27-F: The New York State HIV Confidentiality Law.
[xx] Tao G, Branson BM, Kassler WJ et al. Rates of receiving HIV test results: data from the US National Health Interview Survey for 1994 and 1995. J Acquir Immune Defic Syndr 1999;22:395-400.
[xxi] Landis SE, Schoenbach VJ, Weber DJ et al. Results of a randomized trial of partner notification in cases of HIV infection in North Carolina. New Engl J Med 1992;326:101-06.
[xxii] Bayer R, Toomey KE. HIV prevention and the two faces of partner notification Am J Public Health 1992;82:1158-64.
[xxiii] Mofenson LM, Lambert JS, Stiehm ER et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. N Engl J Med 1999;341:385-93.
[xxiv] Nduati R, John G, Mbori-Ngacha D et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000;283:1167-74.
[xxv] Weinhardt LS. Carey MP, Johnson BT et al. Effects of HIV counseling and testing on sexual risk behavior: a meta-analytic review of published research, 1985-1997. Am J Public Health 1999;89:1397-405.
[xxvi] Sogolow E, Semaan S, Johnson WD et al. Effects of US-based HIV interventions on safer sex: meta-analyses, over all and for populations, age groups, and settings. Int Conf AIDS 1998;12:239 (abstract no 14283).
[xxvii] Semaan S, Des Jarlais DC, Sogolow ED et al. A meta-analysis of the impact of HIV risk reduction interventions on safer sex behaviors of drug users. Int Conf AIDS 1998;12:232 (abstract no 253/14250).
[xxviii] Gerbert B, Herzig K, Volberding P. Counseling patients about HIV risk from oral sex. J Gen Int Med 1997;12:698-704.
[xxix] Silverman BG, Gross TP. Use and effectiveness of condoms during anal intercourse. A review. Sex Transm Dis 1997;24:11-17.
[xxx] Wingood GM, DiClemente RJ. HIV sexual risk reduction interventions for women: a review. Am J Prev Med 1996;12:20-17.
[xxxi] Davis KB, Weller SC. The effectiveness of condoms in reducing heterosexual transmission of HIV. Fam Plann Perspect 1999;31:272-79.
[xxxii] Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339; 33-39.
[xxxiii] Jolles S, Kinloch de Loes S, Johnson MA et al. Primary HIV-1 infection: a new medical emergency? BMJ 1996;312:1243-44.
[xxxiv] Schacker T, Collier AC, Hughes J et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 1996;125:257-64.
[xxxv] Quinn TC. Acute primary HIV infection. JAMA 1997;278:58-62.
[xxxvi] Vanhems P, Toma E. Recognizing primary HIV-1 infection. Infect Med 1999;16:104-08.
[xxxvii] Lapins J, Sindback S, Lidbrink et al. Mucocutaneous manifestations in 22 consecutive cases of primary HIV-1 infection. Br J Derm 1996;134:257-61.
[xxxviii] Niu M, Jermano JA, Reichelderfer P et al. Summary of the National Institutes of Health workshop on primary human immunodeficiency virus type 1 infection. AIDS Res and Hum Retrov 19939:913-24.
[xxxix] Havlichek DH, Hage-Korbane A. Ann Int Med 1999;131:794 [letter].
[xl] Roland ME. Post-exposure prophylaxis following sexual or injection drug use exposure to HIV: current knowledge and future research strategies. J of HIV Ther 1998;3:17-20.
[xli] PEPnet is an excellent website developed by UCSF: http://epi-center.ucsf.edu/PEP/pepnet.html
[xlii] Cardo DM, Culver DH, Ciesielski CA et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 1997;337:1485-90.
[xliii] Lurie P, Miller S, Hecht F et al. Post-exposure prophylaxis after nonoccupational HIV exposure: clinical, ethical and policy considerations. JAMA 1998;280:1769-73.
[xliv] Katz MH, Gerberding JL. The care of persons with recent sexual exposure to HIV. Ann Int Med 1998;128:306-12.