Warning:

This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:

• STD Treatment Guidelines   at http://www.cdc.gov/STD/treatment

---

1993 Sexually Transmitted Diseases Treatment Guidelines

09/24/1993

SUGGESTED CITATION
Centers for Disease Control and Prevention. 1993 Sexually
transmitted diseases treatment guidelines. MMWR 1993;42(No. RR-14):
{inclusive page numbers}.

CIO Responsible for this publication:
National Center for Prevention Services,
Division of Sexually Transmitted Diseases and HIV Prevention

HIV INFECTION AND EARLY INTERVENTION
     
     Infection with HIV produces a spectrum that progresses from no
apparent illness to AIDS as a late manifestation. The pace of
disease progression is variable. The median time between infection
with HIV and the development of AIDS among adults is 10 years, with
a range from a few months to greater than or equal to 12 years.
Most adults and adolescents infected with HIV remain symptom-free
for long periods, but viral replication can be detected in
asymptomatic persons and increases substantially as the immune
system deteriorates. Most people who are infected with HIV will
eventually have symptoms related to the infection. In cohort
studies of adults infected with HIV, data indicated that symptoms
developed in 70%-85% of infected adults, and AIDS developed in 55%-
62% within 12 years after infection. Additional cases are expected
to occur among those who have remained AIDS-free for greater than
12 years.

     Greater awareness of risky behaviors by both patients and
health-care providers has led to increased testing for HIV and
earlier diagnosis of early HIV infection, often before symptoms
develop (though emotional or psychological problems may occur).
Such early identification of HIV infection is important for several
reasons. Treatments are available to slow the decline of immune
system function. Persons who are infected with HIV and altered
immune function also are at increased risk for infections such as
tuberculosis (TB), bacterial pneumonia, and Pneumocystis carinii
pneumonia (PCP), for which preventive measures are available.
Because of its effect on the immune system, HIV affects the
diagnosis, evaluation, treatment, and follow-up of many other
diseases and may affect the efficacy of antimicrobial therapy for
some STDs. Close clinical follow-up after treatment for STDs is
imperative.

     During early infection, persons with HIV and their families
can be educated about the disease and become linked with a support
network that addresses their needs and with care systems effective
in maintaining good health and delaying the onset of symptoms.
Early diagnosis also offers the opportunity for counseling and for
assistance in preventing the transmission of HIV infection to
others.

     For the purpose of these recommendations, early intervention
for HIV is defined as care for persons infected with HIV who are
without symptoms. However, recently detected HIV infection may not
have been recently acquired. Persons newly diagnosed with HIV may
be at many different stages of the infection. Therefore, early
intervention also involves assuming the responsibility for
coordinating care and for arranging access to resources necessary
to meet the medical, psychological, and social needs of persons
with more advanced HIV infection.

Diagnostic Testing for HIV-1 and HIV-2
     
     HIV infection is most often diagnosed by using HIV-1 antibody
tests. Antibody testing begins with a sensitive screening test such
as the enzyme-linked immunosorbent assay (ELISA) or a rapid assay.
If confirmed by Western blot or other supplemental test, a positive
antibody test means that a person is infected with HIV and is
capable of transmitting the virus to others. HIV antibody is
detectable in greater than or equal to 95% of patients within 6
months of infection. Although a negative antibody test usually
means a person is not infected, antibody tests cannot rule out
infection that occurred less than 6 months before the test.

     Since there is transplacental passage of maternal HIV
antibody, antibody tests for HIV are expected to be positive in the
serum of both infected and uninfected infants born to a
seropositive mother. Passively acquired HIV antibody falls to
undetectable levels among most infants by 15 months of age. A
definitive determination of HIV infection for an infant less than
15 months of age should be based either on the presence of antibody
to HIV in conjunction with a compatible immunologic profile and
clinical course or on laboratory evidence of HIV in blood or
tissues by culture, nucleic acid, or antigen detection.

     Specific recommendations for the diagnostic testing of HIV are
listed below:

--   Informed consent must be obtained before an HIV test is
     performed. Some states require written consent. See HIV Prevention
     Counseling for a discussion of pretest and posttest counseling.

--   Positive screening tests for HIV antibody must be confirmed by
     a more specific confirmatory test (either the Western blot assay or
     indirect immunofluorescence assay {IFA}) before being considered
     definitive for confirming HIV infection.

--   Persons with positive HIV tests must receive medical and
     psychosocial evaluation and monitoring services, or be referred for
     these services.

     The prevalence of HIV-2 in the United States is extremely low,
and CDC does not recommend routine testing for HIV-2 in settings
other than blood centers, unless demographic or behavioral
information suggests that HIV-2 infection might be present. Those
at risk for HIV-2 infection include persons from a country in which
HIV-2 is endemic or the sex partners of such persons. (As of July
1992, HIV-2 was endemic in parts of West Africa and an increased
prevalence of HIV-2 had been reported in Angola, France,
Mozambique, and Portugal.) Additionally, testing for HIV-2 should
be conducted when there is clinical evidence or suspicion of HIV
disease in the absence of a positive test for antibodies to HIV-1
(6).

Counseling for Patients with HIV Infection
     
     Behavioral and psychosocial services are an integral part of
HIV early intervention. Patients usually experience emotional
distress when first being informed of a positive HIV test result,
and also later when notified of changes in immunologic markers,
when antiviral or prophylactic therapy is initiated, and when
symptoms develop. Patients face several major adaptive challenges:
a) accepting the possibility of a curtailed life span, b) coping
with others' reactions to a stigmatizing illness, c) developing
strategies for maintaining physical and emotional health, and d)
initiating changes in behavior to prevent HIV transmission. Many
patients also require assistance with making reproductive choices,
gaining access to health services and health insurance, and
confronting employment discrimination.

     Interrupting HIV transmission depends upon changes in behavior
by those persons at risk for transmitting or acquiring infection.
Though some viral culture studies suggest that antiviral treatment
reduces viral burden, clinical data are insufficient to determine
whether therapy might reduce the probability of transmission.
Infected persons, as potential sources of new infections, must
receive extra attention and support to help break chains of
transmission and to prevent infection of others. Targeting behavior
change programs toward HIV-infected persons and their sex partners,
or those with whom they share needles, is an important adjunct to
current AIDS prevention efforts.

     Specific recommendations for counseling patients with HIV
infection are listed below:

--   Persons who test positive for HIV antibody should be counseled
     by a person who is able to discuss the medical, psychological, and
     social implications of HIV infection.

--   Appropriate social support and psychological resources should
     be available, either on site or through referral, to assist
     patients in coping with emotional distress.

--   Persons who continue to be at risk for transmitting HIV should
     receive assistance in changing or avoiding behaviors that can
     transmit infection to others.

Initial Evaluation and Planning for Care
     
     Practice settings for offering early HIV care are variable,
depending upon local resources and needs. Primary-care providers
and outpatient facilities must ensure that appropriate resources
are available for each patient and must avoid fragmentation of
care; it is preferable for persons with HIV infection to receive
care from a single source that is able to provide comprehensive
care for all stages of HIV infection. But the limited availability
of such resources often results in the need to coordinate care
among outpatient, inpatient, and specialist providers in different
locations. Because of the progressive nature of HIV and the
increased risk for bacterial infections, including TB -- even
before HIV infection becomes advanced -- it is essential to
establish specific provisions for handling the medical,
psychological, and social problems likely to arise at any stage of
infection. An important component of early intervention is
effective linkage with referral settings where off-hours care and
specialty services are available. Development of an appropriate
plan for care involves the following:

--   Identification of patients in need of immediate medical care
     (e.g., patients with symptomatic HIV infection or emotional crisis)
     and of those in need of antiretroviral therapy or prophylaxis for
     opportunistic infections (e.g., PCP).

--   Evaluation for the presence of diseases associated with HIV,
     such as TB and STDs.

--   Administration of recommended vaccinations.

--   Case management or referral for case management.

--   Counseling (see Counseling for Patients with HIV Infection).

     The CD4+ T-lymphocyte count is the best laboratory indicator
of clinical progression, and comprehensive management strategies
for HIV infection are typically stratified by CD4 count. Either the
absolute number or the percentage of CD4+ T cells may be
determined. CD4+ percentage is more consistent than absolute CD4+
count with successive measurements for the same person and less
variable with delays in specimen processing. However, most clinical
trials have used absolute CD4+ count to evaluate the need for and
timing of therapeutic interventions. Patients with CD4+ counts
greater than 500/uL usually do not demonstrate evidence of clinical
immunosuppression. Patients with 200-500 CD4+ cells/uL are more
likely to develop HIV-related symptoms and to require medical
intervention. Patients with CD4+ counts less than 200 cells/uL, and
those with higher CD4+ counts who develop thrush or unexplained
fever (temperature greater than 37.8 C for greater than or equal to
2 weeks) are at increased risk for developing complicated HIV
disease. Such patients should be managed in a comprehensive
treatment setting with access to specialty resources and
hospitalization.

     Providers unable to offer therapeutic management of HIV may
use the initial evaluation to identify the need for prompt referral
to appropriate resources. The initial evaluation of HIV-positive
patients should include the following essential components:

--   A detailed history, including sexual history, substance abuse
     history, and a review of systems for specific HIV-related symptoms.

--   A physical examination; for females, this examination should
     include a gynecologic examination.

--   For females, testing for N. gonorrhoeae, C. trachomatis, a
     Papanicolaou (Pap) smear, and wet mount examination of vaginal
     secretions.

--   A syphilis serology.

--   A CD4+ T-lymphocyte analysis.

--   Complete blood and platelet counts.

--   A purified protein derivative (PPD) tuberculin skin test by
     the Mantoux method and anergy testing with two delayed-type
     hypersensitivity (DTH) antigens (Candida, mumps, or tetanus toxoid)
     administered by the Mantoux method or a multipuncture device.

--   A thorough psychosocial evaluation, including ascertainment of
     behavioral factors indicating risk for transmitting HIV and
     elucidation of information about any partners who should be
     notified about possible exposure to HIV.

Preventive Therapy for TB
     Studies conducted among persons with and without HIV infection
have suggested that HIV infection can depress tuberculin reactions
before signs and symptoms of HIV infection develop. Cutaneous
anergy (defined as skin test response of less than or equal to 3 mm
to all DTH antigens) may be present among greater than or equal to
10% of asymptomatic persons with CD4+ counts greater than 500
cells/uL, and among greater than 60% of persons with CD4+ counts
less than 200.

     HIV-positive persons with a PPD reaction greater than or equal
to 5 mm induration are considered to be infected with M.
tuberculosis and should be evaluated for preventive treatment with
isoniazid after active TB has been excluded. Anergic persons whose
risk for tuberculous infection is estimated to be greater than or
equal to 10%, based on available prevalence data, also should be
considered for preventive therapy. For further details regarding
evaluation of patients for TB, refer to Purified Protein Derivative
(PPD-tuberculin anergy) and HIV Infection: Guidelines for Anergy
Testing and Management of Anergic Persons at Risk of Tuberculosis
(7).

     The preliminary results from a randomized clinical trial
suggest that treatment with isoniazid is effective for preventing
active TB among HIV-infected persons. The usual regimen is
isoniazid 10 mg/kg daily, up to a maximum adult dose of 300 mg
daily. Twelve months of isoniazid preventive treatment is
recommended for persons with HIV infection. For further details
regarding preventive therapy for TB, refer to The Use of Preventive
Therapy for Tuberculous Infection in the United States (8) and
Management of Persons Exposed to Multidrug-Resistant Tuberculosis
(9).

Recommended Immunizations for Adults and Adolescents
     Specific recommendations for immunization of persons infected
with HIV are listed below:

--   Pneumococcal vaccination and an annual influenza vaccination
     should be administered.

--   Persons at increased risk for acquiring HBV and who lack
     evidence of immunity may receive a three-dose schedule of hepatitis
     B vaccine, with postvaccination serologic testing between 1 and 6
     months after the vaccination series.

     Recommendations for vaccinating HIV-infected persons are based
on expert opinions and consensus of the Advisory Committee on
Immunization Practices (ACIP). No clinical data exist to document
the efficacy of inactivated vaccines among HIV-infected persons,
and pneumococcal vaccine failures have been reported. However, the
use of inactivated vaccines may be beneficial for persons with HIV
infection and there is no evidence that they are harmful.
Immunogenicity studies have suggested a generally poorer response
among HIV-infected persons, with higher response rates among
asymptomatic persons than among those with advanced HIV disease.

     Current evidence indicates that HIV infection does not
increase susceptibility to HBV, nor does it increase the severity
of clinical disease. The presence of HIV infection is not an
indication for hepatitis B vaccine, but HIV-infected persons are at
increased risk for becoming chronic carriers after hepatitis B
infection. Because the routes of transmission of HBV parallel those
of HIV, efforts to modify risky behaviors must be the primary focus
of prevention efforts. However, vaccine should be administered to
HIV-infected patients who continue to have a high likelihood for
HBV exposure.

     Persons with HIV infection also are at increased risk for
invasive Haemophilus influenzae type B (Hib) disease and for
complications from measles. Immunization against Hib and measles
should be considered for asymptomatic HIV-infected persons who may
have an increased risk for exposure to these infections. For
further details on immunization of HIV-infected patients, refer to
Recommendations of the Advisory Committee on Immunization Practices
(ACIP): Use of Vaccines and Immune Globulins in Persons with
Altered Immunocompetence (10).

Follow-Up Evaluation
     
     There have been no controlled studies to serve as the basis
for recommending specific follow-up tests or follow-up intervals.
The suggested frequency of monitoring is based on the slow decrease
in CD4+ counts observed among patients in cohort studies, but
should be modified depending on the patient's psychological status,
the presence of symptoms, or both. Repeat evaluation for STDs also
is important in the follow-up of HIV-infected persons and should be
performed on all persons who continue to be sexually active.
Follow-up evaluation should be performed every 6 months and should
include the following:

--   An interim history and physical examination;

--   A complete blood count, platelet count, and lymphocyte subset
     analysis;

--   Re-evaluation of psychosocial status and behavioral factors
     indicating risk for transmitting HIV.

     To follow CD4+ measurements, providers should use the same
laboratory and, optimally, obtain each specimen at the same time
each day. When unexpected or discrepant results are obtained or
when major treatment decisions are to be made, health-care
providers should consider repeating the CD4+ measurement after at
least 1 week.

     More frequent laboratory monitoring, every 3-4 months, is
indicated if CD4+ results indicate a patient is close to a point
when a clinical intervention may be indicated.

Continuing Management of Patients with Early HIV Infection
     
     Providing comprehensive, continuing management of patients
with early HIV infection can include additional diagnostic studies
(e.g., chest x-ray, serum chemistry, antibody testing for
toxoplasmosis and hepatitis B), antiretroviral therapy and
monitoring, and PCP prophylaxis. Treatment of HIV infection and
prophylaxis against opportunistic infections continue to evolve
rapidly. This treatment should be undertaken in consultation with
physicians who are familiar with the care of persons with HIV
infection. The complete therapeutic management of HIV infection is
beyond the scope of this document.

Antiretroviral Therapy
     The optimal time for initiating antiretroviral therapy has not
yet been established. Zidovudine (ZDV) at a dose of 500 mg/day (100
mg orally every 4 hours while the patient is awake) has been
recommended for symptomatic persons with less than 500 CD4+
T-cells/uL, and for asymptomatic persons with less than 300 CD4+
T-cells/uL. This recommendation is based on results of short-term
follow-up in three randomized clinical trials demonstrating that
the initiation of ZDV therapy delays progression to advanced
disease. Evidence for improved long-term survival after early
treatment is less conclusive. The effects of ZDV may be transient,
possibly because of the development of viral resistance or other
factors. Sequential or combination therapy with other
antiretroviral agents could be more efficacious.

     Whether other daily dosages, dose schedules, or dosages based
on body weight would result in greater therapeutic benefit or few
side effects is not known. Providers should work with patients to
design a treatment strategy that is both clinically sound and
appropriate for each individual patient's needs, priorities, and
circumstances. An initial dose of 600 mg in divided doses has been
recommended by a panel of experts convened by the National
Institute of Allergy and Infectious Diseases (NIAID). Preliminary
data suggest ZDV can yield therapeutic results when the dosing
interval is increased to 8 hours, and at doses of 200 mg three
times daily. Antiretroviral efficacy is diminished at doses less
than 300 mg/day, and it has been suggested that higher oral doses
may be required to achieve effective levels in the central nervous
system.

     There are no data to support the use of antiretroviral drugs
other than ZDV as initial therapy. Didanosine (DDI) is recommended
for persons who are intolerant of ZDV or who experience progression
of symptoms despite ZDV. Two 100 mg tablets of DDI are recommended
every 12 hours for persons who weigh greater than or equal to 60
kg; the recommended dose for adults less than 60 kg is one 100 mg
tablet and one 25 mg tablet every 12 hours. Two tablets are
recommended at each dose so that adequate buffering is provided to
prevent gastric acid degradation of the drug.

     Benefits have been reported from other antiretroviral
regimens, including treatment with combinations of ZDV, DDC
(dideoxycytidine {zalcitabine}), and DDI, or switching therapy to
DDI after long-term therapy with ZDV. Experience with these
alternatives is insufficient to serve as a basis for
recommendations. Providers managing patients who are taking
antiretroviral therapy should be familiar with evidence being
developed in several clinical trials. Current information is
available from the NIAID AIDS Clinical Trials Information Service,
1-800-TRIALS-A.

     Side effects that are serious (e.g., anemia, cytopenia,
pancreatitis, and peripheral neuropathy) and uncomfortable (e.g.,
nausea, vomiting, headaches, and insomnia) are common during
antiretroviral therapy. Although hematologic toxicity from ZDV is
less common with the lower doses recommended, approximately 2% of
patients who receive 500 mg/day manifest severe anemia by the 18th
month of treatment -- most within the 3rd through 8th month of
treatment. Careful hematologic monitoring of patients receiving ZDV
is recommended.

PCP Prophylaxis
     Adults and adolescents with less than 200 CD4+ T-cells/uL or
with constitutional symptoms, such as thrush or unexplained fever
greater than 100 F for greater than or equal to 2 weeks, and any
patient with a previous episode of PCP should receive PCP
prophylaxis. Prophylaxis should be continued for the lifetime of
the patient.

     Based upon evidence from randomized controlled clinical
trials, the Public Health Service Task Force on Antipneumocystis
Prophylaxis has recommended the following regimens for PCP
prophylaxis among adults and adolescents:

--   Oral trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of one
     double-strength tablet (800 mg SMX and 160 mg TMP) orally once a
     day.

--   For patients unable to tolerate TMP-SMX: aerosol pentamidine
     administered by either the Respirgard II nebulizer regimen (300 mg
     once a month) or the Fisoneb nebulizer (initial loading regimen of
     five 60 mg doses during a 2-week period, followed by a 60 mg dose
     every 2 weeks).

     The efficacy of alternatives for patients unable to tolerate
TMP-SMX, including dapsone 100 mg orally once a day and sulfa
desensitization, has not been studied extensively. For further
details on PCP prophylaxis, refer to Recommendations for
Prophylaxis Against Pneumocystis carinii pneumonia for adults and
adolescents infected with human immunodeficiency virus (11).

Management of Sex Partners
     
     The rationale for implementing partner notification is that
early diagnosis and treatment of HIV infection may reduce morbidity
and offers the opportunity to encourage risk-reducing behaviors.
Two complementary notification processes, patient referral and
provider referral, can be used to identify partners. With patient
referral, patients inform their own partners directly of their
exposure to HIV infection. With provider referral, trained health
department personnel locate partners on the basis of the names,
descriptions, and addresses provided by the patient. During the
notification process, the anonymity of patients is protected; their
names are not revealed to sex or needle-sharing partners who are
notified. Many state health departments provide assistance with
provider referral partner notification upon request.

     One randomized trial suggested that provider referral is more
effective in notifying partners than patient referral. In that
trial, 50% of partners in the provider referral group were
notified, yet only 7% of partners were notified by subjects in the
patient referral group. However, few data demonstrate whether
behavioral change takes place as a result of partner notification
and many patients are reluctant to disclose the names of partners
because of concern about discrimination, disruption of
relationships, and loss of confidentiality for the partners.

     When referring to those persons infected with HIV, the term
"partner" includes not only sex partners but also injecting drug
users who share needles or other injecting equipment. Partner
notification is a means of identifying and concentrating risk-
reduction efforts on persons at high risk for contracting or
transmitting HIV infection. Partner notification for HIV infection
must be confidential and should depend upon the voluntary
cooperation of the patient.

     Specific recommendations for implementing partner notification
procedures are listed below:

--   Persons who are HIV-positive should be encouraged to notify
     their partners and to refer them for counseling and testing.
     Providers should assist in this process, if desired by the patient,
     either directly or through referral to health department partner
     notification programs.

--   If patients are unwilling to notify their partners or if it
     cannot be assured that their partners will seek counseling,
     physicians or health department personnel should use confidential
     procedures to assure that the partners are notified.

Special Considerations

Pregnancy
     Women who are HIV-infected should be specifically informed
about the risk for perinatal infection. Current evidence indicates
that 15%-39% of infants born to HIV- infected mothers are infected
with HIV, and the virus also can be transmitted from an infected
mother by breastfeeding. Pregnancy among HIV-infected patients does
not appear to increase maternal morbidity or mortality.

     Women should be counseled about their options regarding
pregnancy. The objective of counseling is to provide HIV-infected
women with current information for making reproductive decisions,
analogous to the model used in genetic counseling. Contraceptive,
prenatal, and abortion services should be available on site or by
referral.

     Minimal information is available on the use of ZDV or other
antiretroviral drugs during pregnancy. Trials to evaluate its
efficacy in preventing perinatal transmission and its safety during
pregnancy are being conducted. A case series of 43 pregnant women
has been published; dosages of ZDV ranged from 300 to 1,200 mg/day.
ZDV was well tolerated and there were no malformations among the
newborns in this series. Although this observation is encouraging,
this series of negative case reports cannot be used to infer that
ZDV is not teratogenic.

     Burroughs Wellcome Co. and Hoffmann-LaRoche, Inc., in
cooperation with CDC, maintain a registry to assess the effects of
the use of ZDV and DDC during pregnancy. Women who receive either
ZDV or DDC during pregnancy should be reported to this registry
(1-800-722-9292, ext. 58465).

HIV Infection Among Infants and Children
     Infants and young children with HIV infection differ from
adults and adolescents with respect to the diagnosis, clinical
presentation, and management of HIV disease. For example, total
lymphocytes and absolute CD4+ cell counts are much higher in
infants and children than in healthy adults and are age dependent.
Specific indications and dosages for both antiretroviral and
prophylactic therapy have been developed for children (12). Other
modifications must be made in health services that are recommended
for infants and children, such as avoiding vaccination with live
oral polio vaccine when a child (or close household contact) is
infected with HIV.

     State laws differ regarding consent of minor persons ( less
than 18 years of age) for HIV counseling and testing, evaluation,
treatment services, and participation in clinical trials. Although
most adolescents receive adult doses of antiretroviral and
prophylactic therapy, there are no data on modification of these
dosages during puberty. Management of infants, children, and
adolescents -- who are known or suspected to be infected with HIV
-- requires referral to, or close consultation with, physicians
familiar with the manifestations and treatment of pediatric HIV
infection.

---