Comparison of HIV-1 nef and gag variations and host HLA characteristics as determinants of disease progression among HIV-1 vertically infected Kenyan children

Objectives: Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children. Methods: Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at 10 years of age (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and the HLA class I-related epitopes were compared between the two groups. Results: Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20%of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3 region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A∗74:01, A∗32:01 and A∗26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B∗45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP. Conclusions: Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children. © 2015 Saina et al

Lower prevalence of Entamoeba species in children with vertically transmitted HIV infection in Western Kenya

A cross-sectional molecular epidemiological study of Entamoeba species was conducted among asymptomatic Kenyan children with (n=123) and without (n=111) HIV infection. The prevalence of E. histolytica was low (0.4%). Entamoeba species infection was inversely related with HIV infection [HIV(+): 29.3% vs. HIV(-): 55.0%, P<0.001]: multiple-species infection was related to higher CD4+ T-cell counts. Thus, HIV infection is not a risk factor for amebic infection, and multiple-species infection can be an indicator of better immune status. © 2016 Wolters Kluwer Health, Inc

Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis

Introduction: Antiretroviral therapy plays a major role in reducing the impact of Human Immunodeficiency Virus/Acquired Immune Disease Syndrome, especially in resource-limited settings. However, without proper infrastructure, it has resulted in emergence of drug resistance mutations in infected populations. To determine drug resistance mutations among patients attending a comprehensive care facility in Nairobi, 65 blood samples were successfully sequenced. Methods: Whole blood samples were also tested for CD4+T-cell count and plasma HIV-1 RNA Viral load. Drug-resistance testing targeting the HIV-1 RT gene was determined. Patients were on first line ART that consisted of two NRTIs, and one NNRTI. Results: Females were younger (mean 42) than males (mean 45) and lower median CD4+ counts (139 cells/μl) than males (152 cells/μl). The prevalence of drug resistance mutations (any major mutation) in this population was 23.1% (15/65). Major NRTI mutations were detected in 11 patient samples, which included M184V (n = 6), M41L (n=3), D67N (n=2), K219Q (n=3) and T215F (n=2). Major NNRTI mutations were detected in 14 patient samples. They included K103N (n = 10), G190A (n = 1), Y181C (n = 1) and Y188L (n = 1). Conclusion: Presence of major mutations in this study calls for proper laboratory infrastructure to monitor treatment as well as regular appraisals of available regimens

Characterization of occult hepatitis B in high-risk populations in Kenya.

Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver or serum in the absence of detectable HBV surface antigen (HBsAg). OBI poses a risk for the development of cirrhosis and hepatocellular carcinoma. The prevalence of OBI in Kenya is unknown, thus a study was undertaken to determine the prevalence and molecular characterization of OBI in Kenyan populations at high risk of HBV infection. Sera from two Nairobi cohorts, 99 male sex workers, primarily having sex with men (MSM-SW), and 13 non-MSM men having HIV-positive partners, as well as 65 HBsAg-negative patients presenting with jaundice at Kenyan medical facilities, were tested for HBV serological markers, including HBV DNA by real-time PCR. Positive DNA samples were sequenced and MSM-SW patients were further tested for hepatitis C virus (HCV) infection. Of the 166 HBsAg-negative samples tested, 31 (18.7%; 95% confidence interval [CI] 13.5-25.3) were HBV DNA positive (i.e., occult), the majority (20/31; 64.5%) of which were HBV core protein antibody positive. HCV infection was not observed in the MSM-SW participants, although the prevalence of HBsAg positivity was 10.1% (10/99; 95% CI 5.6-17.6). HBV genotype A was predominant among study cases, including both HBsAg-positive and OBI participants, although the data suggests a non-African network transmission source among MSM-SW. The high prevalence of HBV infection among MSM-SW in Kenya suggests that screening programmes be instituted among high-risk cohorts to facilitate preventative measures, such as vaccination, and establish entry to treatment and linkage to care

Comparison of HIV-1 <i>nef</i> and <i>gag</i> Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children

<div><p>Objectives</p><p>Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children.</p><p>Methods</p><p>Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at <5 years of age (rapid progressors; RP), and 32 (17 male/15 female) who started at >10 years of age (slow progressors; SP). Sequence variations in the HIV-1 <i>gag</i> and <i>nef</i> genes and the HLA class I-related epitopes were compared between the two groups.</p><p>Results</p><p>Based on <i>nef</i> sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20% of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP₃ region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A*74:01, A*32:01 and A*26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B*45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP.</p><p>Conclusions</p><p>Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children.</p></div

Comparison of the number of predicted HLA class I related Gag epitopes.

<p>The total number of Gag epitopes (of 8–14 amino acids in length) recognized <i>in silico</i> by an individual’s HLA-A (A), HLA-B (B), and HLA-C (C), as well as epitopes of specific lengths that showed statistically significant differences, including 9-mer-HLA-A (D), 11-mer-HLA-B (E), and-HLA-C (F). Closed circles represent rapid progressors and open circles represent slow progressors. Horizontal lines indicate the median number of epitopes. Statistical analyses were performed using the Mann-Whitney U test.</p

The proportion of patients with substitutions in Gag functional domains.

<p>The proportion of patients with substitutions in Gag functional domains.</p