The epidemiology and clinical correlates of HIV‐1 co‐receptor tropism in non‐subtype B infections from India, Uganda and South Africa

Abstract

BackgroundThe 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.MethodsHIV-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+ and CD8+ T cell counts.ResultsCCR5-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+ count.ConclusionsR5 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+ count correlated with R5 prevalence, while treatment experience was associated with increased non-R5 infection in all subtypes.

Non-R5-tropic HIV-1 in subtype A1 and D infections were associated with lower pretherapy CD4+ cell count but not with PI/(N)NRTI therapy outcomes in Mbarara, Uganda

“…Previous studies tend to focus on only two of the three factors at a time: In terms of the relationship between HIV-1 subtype and pre-therapy CD4 count, our observation agrees with previous reports that pre-therapy subtype D infections are “more aggressive” than subtype A1 by being associated with a lower baseline CD4 count [2,3]. In terms of the relationship between HIV-1 subtype and viral tropism, our observation agrees with previous reports that subtype D is associated with a higher prevalence of non-R5-tropic viruses [7,8,11–14]. In terms of the relationship between viral tropism and pre-therapy CD4 count, our observation agrees with previous reports that non-R5 infections are associated with lower CD4 count [10,27,28].…”

“…HIV can be classified by its co-receptor usage: “R5-tropic HIV” infects host cells that express cell surface CCR5 receptors, whereas strains that can use alternative co-receptors including CXCR4 are collectively termed “non-R5-tropic HIV” [5,6]. Detection of non-R5-tropic HIV virus is associated with lower CD4 counts [7,8], a more advanced disease stage and a faster disease progression, but there is no clear impact of co-receptor usage on antiretroviral therapy response [9]. In a predominantly subtype B chronically infected cohort, non-R5-tropic HIV-1 was associated with a poorer pre-therapy baseline viral load and CD4 count, but tropism was not associated with therapy outcomes examined including time to virologic suppression, time to virologic rebound, time to CD4 decline and time to nonaccidental death [10].…”

“…Both subtype D and non-R5 are independently associated with a faster disease progression [2,3,7,8]. Numerous studies have shown that subtype D viruses are more likely to be non-R5-tropic [7,8,11–14], and non-R5-tropic subtype D infections in Ugandan babies is linked to higher mortality [12]. These observations lead to the question of whether an infection that is both subtype D and non-R5 would lead to synergistic increase in disease progression.…”

HIV population genotypic tropism testing and its clinical significance

“…Recently published data show differences in the distribution of co-receptor tropism in different HIV-1 subtypes [41][42][43][44][45][46][47]. The HIV-GRADE network [48] has analysed data from clinical routine diagnostics and observed differences in the distribution of co-receptor tropism in the distinct subtypes [49] as shown in Fig.…”

Deteksi Natrium/Iodide Symporter (NIS) pada Galur Sel Kanker Payudara SKBR3 dengan Imunositofluoresens

“…Hal yang sama dengan penelitian yang dilakukan di Afrika didapatkan bahwa subtipe non B sering didapatkan pada pasien dengan penyakit derajat berat (stadium AIDS). 19 Proporsi penderita AIDS dengan infeksi oportunistik tuberkulosis sebanyak 60 orang (64%) dan juga penderita AIDS dengan infeksi oportunistik selain TB sebanyak 34 orang (36%). Perbedaan tersebut secara statistik bermakna (p=0,00).…”