Aims: Oral and systemic comorbidities are common in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and are considered to be important predictors of the disease. Cluster of differentiation 4 (CD4) count serves as an important marker for the progression of HIV to AIDS. Our objective was to correlate the oral and systemic comorbidities associated with HIV infection with CD4 count in patients on highly active antiretroviral therapy (HAART). Materials and methods: This was an observational study among 110 HIV-diagnosed patients. The oral and systemic comorbidities were noted and compared to their CD4 counts. A Chi-square analysis was carried out to see the association of oral manifestations. Results: Among the study subjects, 50 (45.5%) participants had a CD4 count of >500 cells/μL, 46 (41.8%) patients had a CD4 count of 200–499 cells/μL, whereas 14 (12.7%) had <200 cells/μL. The major oral manifestations observed were dental caries (n = 30, 60%), periodontitis (n = 25, 50%), and lipoatrophy (n = 25, 50%) in patients with CD4 >500 cells/μL; dental caries (n = 28, 60.90%), intraoral pigmentation (n = 23, 50%), and periodontitis (n = 20, 43.50%) in patients with a CD4 count between 200 and 499; and dental caries (n = 9, 64.30%), periodontitis (n = 7, 50%), and candidiasis 6 (42.90%) among subjects with CD4 counts <200. The most common systemic comorbidity observed was tuberculosis (p < 0.001) and pneumonia (p < 0.003). Conclusion: Early intervention strategies in diagnosis and management for HIV-infected individuals have shown promising results. With the advent of HAART, the quality of life has significantly improved. Clinical significance: The prevalence of oral and systemic comorbidity among HIV-infected patients have declined since the advent of HAART. Oral and general physicians should be able to identify and treat the patients at the earliest, which in turn could reduce the morbidity and mortality rates among those infected with HIV.