General Areas of Study: The following are a list of general areas of study. Specific formal hypotheses will be derived from these study areas as data are collected and specific papers are proposed.

Sample: The following table lists ideal goals for client recruitment to be achieved by individual sites if possible. The final samples may not be as large as stated here if it is impossible for sites to recruit appropriate patients in the time periods allowed for data collection. Individual sites commit to these numbers as ideal targets and not as absolute quotas for data collection.

General Sampling Criteria

• Individuals should be starting protease inhibitors in various combination therapies for the first time.

• Depending upon the experiences of the data collection sites it may be necessary to enroll clients who have started protease inhibitor therapies earlier and then to consider these clients to be a special substudy, possibly with additional retrospective data collection instruments.

• As much as possible, the sample should reflect the general demographics of the program.

• As much as possible, the sample should be balanced between those clients with no prior experience in drug therapies for HIV and those with experience with HIV medications, especially ZDV.

• As much as possible, the sample should include substance abusers (current or past) and those without a history of substance abuse.

• If possible (when less than 100% of new cases are used), women should be "over-sampled" so that the sample is as close to 50% women as possible.

• If possible, approximately equal numbers of clients should be admitted into the study during each of the "enrollment" months (see below).

• Four of the six programs will attempt to enroll 100% of their protease inhibitor cases in the study. For the remaining two sites (AHF, Hopkins), there will be an enrollment of approximately one-third of the quota of patients in each of the three enrollment months. As much as possible, the clinics will attempt to enroll the first patients entering the clinic during those months who are offered protease inhibitors.

• Each site will track the demographics of all clients offered protease inhibitors whether they choose to receive them or not. Similarly, all sites will track the demographics of all clients eligible for the study whether or not they are enrolled in the actual study.

Timeline for Data Collection: The initial entry into the study shall occur in four months. Clients will be followed up at 3-month intervals. The initial study includes 3- and 6-month follow-ups. The 12-month follow-up is listed below as a possibility but there is currently no commitment on the part of HRSA to fund data collection at this time.

Proposed Data Collection Requirements: The data collection primarily uses existing data collection modules which should have been implemented by the majority of the participating sites in a roughly identical way.

Data collection modules 1-73 are covered in the existing Evaluation Module book for HRSA/HAB's SPNS Cooperative Agreement Projects. Data collection modules P1 and P2 are developed and implemented for this study. They are outlined below.

Module P1: Adherence to Protease Inhibitor Therapy Form. Designed to be completed at each medical visit, this form will be a short one-page 5-10 minute set of indicators (collected from patient interview, chart notes, and laboratory tests) that will cover whether the client has been taking the therapies in the proscribed way. Interview variables include patient reports of therapy adherence, problems in taking the drugs, side effects, satisfaction, and brief health rating. Physician coded variables include categories of believed adherence to the therapy. Laboratory test results also coded for each visit including viral load. The interview and laboratory sections need not be completed by the physician.

Module P2: Retrospective Health Interview Covering Service Utilization in the Prior 6 Months. This will be a study admission interview which briefly reviews the patient's history of service utilization, symptoms, HIV-related drug and other therapies, and major systems problems in the previous 6 months. Designed to be administered by a nurse or researcher. Design specification is for data collection to be completed within 15 minutes. The primary reason for this module is to establish a "pre-study" baseline. The repeated administration after six months will help establish a memory validity adjustment when compared to the actual encounter data.

Publication: The publication strategy for this study is as follows. Each site retains its own data and is free to publish papers solely on its own data as it sees fit. Participation in this study does not preclude use of the same data for other studies. Sites agree to pool this data for a series of papers which will be written and authored by Evaluation and Dissemination Center (TMG) staff, staff representatives from the participating clinical sites, and HRSA staff. Order of authorship will be determined by the group using prevailing professional standards for contributions with guidance from HRSA if necessary. It is hoped that the first paper(s) will be prepared immediately after the three month follow-up with subsequent paper(s) after the six month follow-up. Because timeliness is of the essence in conducting this collaborative study, those individuals who participate in group publications commit to participating in conference calls to plan and review drafts of publications, and to review-edit-write publications as a high priority. Some likely papers include ones linked to the four General Study Areas listed above.

Day-to-Day Management: For the purposes of day-to-day management of the study and facilitation of the group research project, the Director of the Evaluation and Dissemination Center is charged with these responsibilities. Decisions shall be made in consultation with HRSA/HAB's SPNS Director and the Clinical (Medical) Director appointed by the data collection sites for the study. Decisions may need to be made on acceptable local variations in protocol, data collection, sampling, and other commonly encountered research issues as well as suggesting study modifications and publications-presentations. No publications-presentations shall be written without the consent of the whole group, or if the whole group is unable to come to a consensus decision, without the express instruction of HRSA as the funding agency. Similarly, no major deviations from the approved study protocol shall be made without the consent of the whole group, or if the whole group is unable to come to a consensus decision, without the express instruction of HRSA as the funding agency.