A Clinical Study of Ixazomib to Reactivate HIV and Reduce HIV Reservoir Size

1. Documented HIV-1 infection.
2. Plasma HIV-1 RNA of 50 copies/mL or lower, for at least 48 weeks prior to study entry while on antiretroviral therapy. One blip above 50 but below 200 copies/mL in the preceding 48 weeks is permitted provided at least two other measurements in that period were 50 copies/mL or lower.
3. Plasma HIV-1 RNA below the lower limit of quantification within 30 days prior to study entry.
4. Receiving antiretroviral therapy for less than 10 years.
5. On antiretroviral therapy for at least 48 weeks prior to study entry, with no interruption of more than 7 consecutive days in the 90 days prior to entry, and no change in regimen within 90 days prior to entry.
6. CD4+ T cell count of at least 500 cells/mm\^3 within 30 days prior to study entry.
7. Laboratory values within 30 days prior to study entry: absolute neutrophil count at least 1,000/mm\^3; hemoglobin at least 10 g/dL (female participants) or at least 11 g/dL (male participants); platelet count at least 75,000/mm\^3; estimated glomerular filtration rate at least 30 mL/min/1.73m\^2; bilirubin no more than 1.5 times the upper limit of normal, or no more than 3 times the upper limit of normal if the isolated elevation is attributable to a participant medication or Gilbert syndrome, or direct bilirubin within the normal range.
8. For participants who can become pregnant, a negative serum or urine pregnancy test within 24 hours prior to study entry.
9. For participants who can become pregnant, agreement to use two methods of contraception from 10 days prior to study entry through 90 days after the last dose of study treatment. Egg donation is prohibited over the same period.
10. For participants whose sexual activity could result in a partner becoming pregnant, agreement to use condoms from 10 days prior to study entry through 90 days after the last dose of study treatment. Sperm donation is prohibited over the same period.
11. Negative hepatitis B surface antigen within 30 days prior to study entry.
12. Negative hepatitis C antibody, or if positive, a negative HCV RNA PCR, within 30 days prior to study entry.

Exclusion Criteria:

1. Untreated, active AIDS-defining illness.
2. Receiving an HIV protease inhibitor or efavirenz as part of the antiretroviral regimen.
3. Current pregnancy or breastfeeding.
4. Receipt of an investigational HIV vaccine or HIV-specific monoclonal antibody, or participation in a trial of any investigational product, within 180 days prior to study entry, or expected participation in such a study during this study.
5. Any current clinically significant acute or chronic medical condition other than HIV infection that in the investigator's opinion would preclude participation.
6. Any history of peripheral neuropathy, or peripheral neuropathy detected during screening.
7. History of an HIV-associated malignancy, including Kaposi sarcoma or lymphoma of any type, treated with systemic chemotherapy or immunotherapy.
8. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery within 36 months prior to study entry, or for whom such therapy is expected within the following 12 months. Surgical removal of minor localized skin cancers is not exclusionary.
9. Use of prohibited medications within 30 days prior to study entry or planned use during study participation.
10. Known allergy, sensitivity, or hypersensitivity to ixazomib or its formulation.
11. Active drug or alcohol use or dependence that, in the investigator's opinion, would interfere with adherence to study requirements.
12. Acute or serious illness requiring systemic treatment or hospitalization within 30 days prior to study entry.
13. Anticipated change in antiretroviral regimen during the 24 weeks following study entry.
14. Current uncontrolled cardiovascular symptoms, including uncontrolled hypertension (systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg), uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 24 weeks prior to study entry.
15. Any serious medical or psychiatric illness that in the investigator's opinion could interfere with completion of protocol treatment.
16. Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of ixazomib, including difficulty swallowing.
17. Previous treatment with ixazomib.
18. Known resistance to two or more classes of antiretrovirals.