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Background: The introduction of C‐C chemokine receptor type‐5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co‐receptor tropism in different HIV‐1 subtypes and geographical locations. This study was undertaken to evaluate HIV‐1 co‐receptor tropism in the developing world where non‐B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions. Methods: HIV‐1‐infected patients were recruited into this prospective, cross‐sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV‐1 subtype and co‐receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4[sup.+] and CD8[sup.+] T cell counts. Results: CCR5‐tropic (R5) HIV‐1 was detected in 96% of treatment‐naïve (TN) and treatment‐experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed‐tropic HIV‐1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4[sup.+] count. Conclusions: R5 HIV‐1 was predominant in TN individuals with HIV‐1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4[sup.+] count correlated with R5 prevalence, while treatment experience was associated with increased non‐R5 infection in all subtypes., Background Human immunodeficiency virus type‐1 (HIV‐1) is characterized by extensive genetic heterogeneity. Molecular epidemiologic studies have demonstrated that globally, the most prevalent forms of HIV‐1 are subtypes (clades) C, B [...]