Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study)

Effective antiretroviral therapy has significantly improved and prolonged the lives of
HIV-infected persons. However, antiretroviral use has also been associated with a diverse
array of "unnatural" metabolic complications and other adverse medical conditions. These
problems, together with subsequent longer survival, have increased patients' risk for
developing renal, hepatic, cardiovascular, neurological, rheumatologic, and other end-organ
diseases, and cancers. Longer survival is also increasing the pool of HIV-infected persons
capable of transmitting the virus, which could accelerate the pace of the U.S. epidemic;
however, the ability of physicians caring for HIV-infected persons to incorporate prevention
into their clinical practices and the effectiveness of this intervention have not been
extensively evaluated.

The goals of the Study to Understand the Natural History of HIV and AIDS ("SUN" Study) are:

- to monitor the incidence of metabolic and other medical complications related to the
treatment of HIV infection and attendant prolonged survival,

- to identify risk factors associated with the development of these metabolic and other
medical complications,

- to monitor the contribution of these complications and other conditions to the
morbidity and mortality of HIV infection, and

- to evaluate the efficacy of a structured program of prevention activities, which are
integrated into the routine medical care of HIV patients to reduce HIV transmission.

The SUN Study is designed to enroll and follow for 5 or more years a cohort of up to 1,000
HIV-infected adults at HIV specialty care centers in four U.S. cities: Denver, Minneapolis,
Providence, and St. Louis. Data will be gathered through longitudinal real-time chart
review, biannual physical examination (e.g., body mass index [BMI], blood pressure),
repeated non-invasive imaging (e.g., dual energy x-ray absortiometry [DEXA] scanning,
carotid ultrasonography) and regularly scheduled laboratory testing (e.g., serum lipids, pap
smears, and urinary microalbumin). Data collection and quality control will be managed by
Cerner Corporation. After sufficient enrollment, (circa 200 persons per site) a structured
prevention program to reduce HIV transmission will be introduced. The impact of this
intervention will be evaluated both subjectively (e.g., self-reported change in behavior on
an audio computer-assisted self-interviewing [ACASI] questionnaire) and objectively (e.g.,
change in sexually transmitted disease [STD] incidence).

Outcomes include determination of the incidence of therapy-related metabolic complications
and other adverse conditions associated with longer survival, identification of risk factors
for these complications and conditions, and reduction in both reported and objective
measures of risky sexual behavior.

Inclusion Criteria:

- Subject is age 18 years or older.

- Subject is HIV-infected as confirmed by positive enzyme immunoassay (EIA) and western
blot testing, by an HIV viral load >5,000 copies, or by genotyping that confirms
infection with HIV.

- For highly active antiretroviral therapy (HAART)-naïve subjects (i.e. persons with no
prior substantial antiretroviral [ARV] exposure):

- Subject's CD4+ cell count is between 100 and 500 cells/mm³

- Subject has not ever received more than 30 days consecutive or non-consecutive
treatment with any ARVs regardless of reason (e.g., pharmacokinetic study,
post-exposure prophylaxis, prevention of vertical transmission in pregnancy).

- For HAART-exposed subjects (i.e. persons who have taken or are taking HAART at the
time of enrollment):

- Subject's CD4+ cell count is >100 cells/mm³

- Subject's previous and/or current treatment with ARVs has consisted only of
HAART (of any duration and in any number of regimens) defined as:

- >3 antiretroviral drugs from at least 2 antiretroviral drug classes
(nucleotide reverse transcriptase inhibitors [NRTI], non-nucleoside reverse
transcriptase inhibitors [NNRTI], protease inhibitors [PI]); or,

- >3 NRTIs.

- Other antiretroviral combinations that in the course of the study are developed and
become accepted as equivalent to best available therapy.

- Subject has received only HAART either as prescribed therapy or in the context of a
supervised study.

- Subject has completed at least two visits within the past year to the clinical
facility where the patient is eligible for enrollment.

- Subject is anticipated to continue receiving care at the clinical facility where she
or he is eligible for enrollment for at least 2 years.

- Subject is able to understand and sign an informed consent.

Exclusion Criteria:

- Subject is pregnant.

- Subject is incarcerated. (footnote 1)

- Within the past 60 days subject has:

- Had an AIDS-defining opportunistic infection or illness.

- Received any chemotherapy or immunomodulating therapy (e.g., glucocorticoids,
interleukin-2, interferon). (footnote 2)

- Subject is expected to live less than 2 years.

- Subject is unable or unwilling to complete any part of the study protocol.

- Subject is considered by the principal investigator to be ineligible for enrollment
for any other reason, including but not limited to remote geographic location,
experience in prior research studies, inconsistency as a historian, etc.

- Subject is unable or refuses to provide informed written consent due to any physical
or psychological incapacity (e.g., persistent vegetative state, mental disability).

Footnotes:

1. Participants will be temporarily suspended from the study while pregnant or
incarcerated after enrollment.

2. Cases where eligibility by these criteria is unclear or requires special
consideration will be referred to the Executive Committee for a final decision.