Changes in the HIV Type 1 Envelope Gene from Non-Subtype B HIV Type 1-Infected Children in Kenya

Abstract

A switch of coreceptor usage from CCR5 to CXCR4 occurs in about half of HIV-1-infected individuals in the natural course of infection. To investigate whether antiretroviral therapy (ART) enhances the coreceptor switch of HIV-1, we genotypically analyzed the env-V3 amino acid sequences from 81 HIV-1-infected children in Kenya whose plasma samples were obtained between 2000 and 2007. Of 41 children on ART, 35 had HIV-1 using CCR5 as a coreceptor at baseline. In 7 (20%) of them HIV-1 switched the coreceptor usage during the follow-up period. The mean duration of ART to the time of coreceptor switch was 2.6 years (range: 0.5-5.2). Of the remaining 40 children without ART, 32 had HIV-1 using CCR5 as a coreceptor at baseline and in 3 (9.4%) HIV-1 switched the coreceptor usage. The mean age of the children with HIV-1 coreceptor switch with and without ART was 7.3 and 9.7 years, respectively. The difference in the rate and age of coreceptor switch between treated and untreated children was not significant (p = 0.38 and 0.31, respectively). Of the HIV-1-infected children, 10 started ART by the age of 5 years (rapid progressors) and 23 did not need ART by the age of 10 years (slow progressors). The rate of coreceptor switch was strongly higher in rapid progressors (40%) than slow progressors (8.7%) (p = 0.053). These results suggest that switching of coreceptor usage from CCR5 to CXCR4 among HIV-1-infected children is not influenced by ART, but by factors responsible for rapid disease progression.

Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic

“…Our data demonstrates a high prevalence of R5-using strains among patients attending Kenyatta National Hospital HIV/AIDS comprehensive care clinic in Nairobi. This finding is in line with our earlier evaluation of HIV-1 coreceptor usage among a sexually transmitted infection clinic attendees and HIV-1 infected infants at a children’s home [19,20]. Our data hence confirms the predominance of R5 strains in HIV infected populations in the country.…”

HIV Type 1 Genetic Diversity and Naturally Occurring Polymorphisms in HIV Type 1 Kenyan Isolates: Implications for Integrase Inhibitors

“…This study agrees with previous molecular epidemiological studies on the predominance of HIV-1 subtype A1 in Kenya. 10,[13][14][15] The HIV-1 subtype A1 samples clustered with reference sequences mainly from Kenya showing that the viruses were probably of Kenyan origin. The samples that were HIV-1 subtype C clustered with reference sequences from South 11 The increase in ART coverage is expected to lead to an increase in drugresistant strains among drug-naive patients.…”

Profile of HIV Type 1 Coreceptor Tropism Among Kenyan Patients from 2009 to 2010

“…11 In this study, 13.4% were X4 variants with an average of 258 CD4 counts detected. The X4 variant populations in the current study were consistent with previous studies.…”

“…Since CCR5 antagonist drugs have no effect on X4 populations, HIV-1 coreceptor tropism must be identified before the initiation of treatment. 11 With 13.4% (X4), 4.5% dual tropic, and 84.1% (R5) variants being detected, it is of clinical value 32 in prescribing CCR5 antagonists. The implementation of ART in resource-limited settings requires the use of standard first-line (two NRTIs + one NNRTI) and second-line (one PI/r + two NRTIs) therapies.…”