Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma

Inclusion Criteria: * Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy * Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion \>= 12 mm or 3 \>= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated * Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria * Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA * Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives) * Absolute neutrophil count (ANC) \>= 1,000/mm\^3; subjects may be receiving growth factor support to meet these criteria * Hemoglobin \>= 8.0 gm/dL; subjects may be receiving growth factor support to meet these criteria * Platelets \>= 100,000/mm\^3 * Total bilirubin =\< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN) * Serum creatinine =\< institutional ULN or creatinine clearance \>= 50 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional ULN * Pre-existing grade 3 or 4 peripheral neuropathy Exclusion Criteria: * KS that is improving in the 4 weeks prior to enrollment * Symptomatic visceral KS (oral and lymph node involvement is eligible) * Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities of daily living is allowable * Eastern Cooperative Oncology Group (ECOG) performance status greater than 2 * Expected survival \< 3 months with standard KS treatments (i.e., radiation, paclitaxel) * Concurrent active opportunistic infection (OI) * Herpes zoster (shingles) outbreak within the last 6 months or inability to take herpes zoster prophylaxis * Patient is =\< 5 years free of another primary malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if the other primary malignancy is a localized squamous or basal cell skin cancer or cervical/anal carcinoma in situ * Acute treatment for an infection or other serious medical illness within 14 days prior to study entry * Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including chemotherapy, radiation therapy, biological therapy, or investigational therapy) within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment * Prior treatment with bortezomib or other investigational proteasome inhibitors * Previous local therapy of any KS indicator lesion within 60 days, unless the lesion has clearly progressed with enlargement since the local therapy * Use of any investigational drug or treatment within 4 weeks prior to randomization * Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance * Hypersensitivity to boron * Subjects with grade III/IV cardiac disease as defined by the New York Heart Association criteria. (e.g., congestive heart failure, myocardial infarction within 6 months of study) * Subject has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis); subjects with known hepatitis B or C infection may be enrolled if they have either documentation of no or minimal fibrosis on liver biopsy or undetectable hepatitis virus on polymerase chain reaction (PCR) * Systemic corticosteroid treatment, other than replacement doses * Female subjects who are pregnant or breast-feeding