• Change in Cognitive Performance Compared to Baseline [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]

  Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:

  1. Grooved Pegboard Dominant Hand (GPD)
  2. Grooved Pegboard Non-dominant hand (GPN)
  3. Choice Reaction Time (CRT)
  4. Sequential Reaction Time (QRT)
  5. Timed Gait (TIG)
  6. Trail Making Part A (TMA)
  7. Trail Making Part B (TMB)
  8. Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline.
  
  

• Change in Global Deficit Z-Score (GDS) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline).
  
  
• Change in Investigator's Clinical Global Impression Score (ICGIS) [ Time Frame: At week 24 ] [ Designated as safety issue: No ]

  Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening.

  For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved.

  
  
• Change in Cognitive Gross Motor Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline).
  
  
• Change in Fine Motor Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline).
  
  
• Change in Psychomotor Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline).
  
  
• Change in Fine Motor/Nonverbal Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline).
  
  
• Change in Information Processing Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline).
  
  
• Change in Verbal Memory Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline).
  
  
• Change in Frontal Systems Function Domain Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline).
  
  
• Change in Karnofsky Performance Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]

  The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks.

  For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created.

  
  
• Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) [ Time Frame: At baseline and weeks 24 ] [ Designated as safety issue: No ]
  The outcome was the 24 week change in CD4 cell count (week 24-baseline).
  
  
• Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The outcome was the 24 week change of CD8 cell counts (week 24-baseline).
  
  
• Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms [ Time Frame: Throughout study up to week 48 ] [ Designated as safety issue: Yes ]
  Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section.
  
  
• Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL).
  
  
• Changes in Instrumental Activities of Daily Living Questionnaire [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline.
  
  
• Changes in Medication Management Test (Modified) [ Time Frame: At baseline and weeks 24 ] [ Designated as safety issue: No ]
  The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management.
  
  
• Markers Including, But Not Limited to, Those of Immune Activation and Oxidative Stress/Apoptosis [ Time Frame: At pre-entry and Week 24 ] [ Designated as safety issue: No ]
  
• Changes in Alternate Psychomotor Function Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline).
  
  
• Changes in Alternate Verbal Memory Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline).
  
  
• Changes in Alternate Frontal Systems Z-Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
  The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline).
  
  

Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.

This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.

There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.