Purpose: Despite antiretroviral therapy, approximately half of individuals with human immunodeficiency virus (HIV) will develop HIV-associated neurocognitive disorder (HAND). Efficiency of brain networks is of great importance for cognitive functioning, since functional networks may reorganize or compensate to preserve normal cognition. This study aims to compare efficiency of the posterior cingulate cortex (PCC) between patients with and without HAND and controls. We hypothesize HAND negative (HAND–) patients will show higher PCC efficiency than HAND positive (HAND+) patients. Methods: A total of 10 HAND + patients were compared with 9 HAND– patients and 17 gender-, age-, and education-matched controls. Resting-state functional MRI was acquired with a 3 Tesla scanner. Local efficiency, a measure of network functioning, was investigated for PCC. Network differences among HAND +, HAND– patients and controls were tested as well as correlations between network parameters and cognitive test performance in different domains. Results: HAND– patients showed significantly increased PCC efficiency compared with healthy controls (p = 0.015). No differences were observed between HAND + patients and either controls (p = 0.327) or HAND– patients (p = 0.152). In HAND– patients, PCC efficiency was positively related with cognitive performance in the attention/working memory domain (p = 0.003). Conversely, in HAND + patients, PCC efficiency was negatively correlated with performance in the abstraction/executive domain (p = 0.002). Conclusion: HAND– patients showed a higher level of PCC efficiency compared with healthy subjects, and PCC efficiency was positively related to cognitive performance. These results support the functional reorganization hypothesis, that increased PCC efficiency is a compensation technique to maintain cognitive functioning.