The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

We previously found an association between faster CD4+ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-alpha (IL-7R alpha) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n = 352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7R alpha single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n = 57). Soluble (s)IL-7R alpha levels were measured by ELISA. In UARTO, IL-7R alpha haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P = 0.020) and no association was found with LMM (P = 0.958). The tagging-SNP for IL-7R alpha haplotype-2 (rs6897932) was associated with decreased sIL-7R alpha (P < 0.001). The haplotypes for the IL-7R alpha. were significantly different in Africans and Caucasians. Using IL-7R alpha genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P = 0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P = 0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7R alpha haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7R alpha SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

We previously found an association between faster CD4+ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-α (IL-7Rα) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n=352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7Rα single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n=57). Soluble (s)IL-7Rα levels were measured by ELISA. In UARTO, IL-7Rα haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P=0.020) and no association was found with LMM (P=0.958). The tagging-SNP for IL-7Rα haplotype-2 (rs6897932) was associated with decreased sIL-7Rα (P<0.001). The haplotypes for the IL-7Rα were significantly different in Africans and Caucasians. Using IL-7Rα genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P=0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P=0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7Rα haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Rα SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.Genes and Immunity advance online publication, 22 September 2011; doi:10.1038/gene.2011.65

Hepatitis C Virus Infection in San Francisco's HIV-infected Urban Poor: High Prevalence but Low Treatment Rates

OBJECTIVE: To measure Hepatitis C Virus (HCV) prevalence, incidence, and initiation of HCV therapy in a representative HIV-infected cohort of the urban poor. DESIGN: Cohort analysis. SETTING: The Research and Access to Care for the Homeless (REACH) Cohort is a systematic sample of HIV-infected marginally housed individuals identified from single-room occupancy hotels, homeless shelters, and free lunch programs in San Francisco. PARTICIPANTS: Two hundred forty-nine participants with 28.9 months (median) of follow-up were studied. Mean age was 44 (range 24 to 75, standard deviation 8.4) years. Eighty-two percent were male, 43% were African-American, 64% were lifetime injection drug users, and 24% had been on the street or in a shelter in the prior month. INTERVENTIONS: We measured HCV testing and treatment history with structured interviews; additionally, participants were tested for HCV antibodies (EIA-2) with RNA viral load confirmation. MAIN RESULTS: At baseline, 172 (69.1%) were HCV-positive and 182 (73.1%) were HCV-positive at follow-up, including 155 (62.2%) with viremia. HCV-positive status was associated with having injected drugs, elevated serum alanine aminotransferase, homelessness in the last 1 year, and more severe depressive symptoms. The incidence of new HCV infection was 4.63% per person-year (ppy; 95% confidence interval, 2.31 to 8.13) in the entire cohort and 16.77% ppy among injection drug users. The prevalence of HCV antibody-negative HCV-viremia was 13.2% (10/76). Nonwhites were less likely to receive HCV testing and subspecialty referral, controlled for drug use and other confounders. Sixty-eight percent (123/182) were aware treatment was available; however, only 3.8% (7/182) or 1.16% ppy received HCV treatment. CONCLUSIONS: While HCV infection is common, HCV treatment is rare in the HIV-HCV coinfected urban poor. Urban poor, nonwhite individuals are less likely to receive HCV testing and subspecialty referral than their white counterparts. Antibody-negative infection may complicate screening and diagnosis in HIV-infected persons

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R &lt;sup&gt;2&lt;/sup&gt; ) on 6-month log &lt;sub&gt;10&lt;/sub&gt; HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (&gt;95%) Av-Adh. Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R &lt;sup&gt;2&lt;/sup&gt; for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R &lt;sup&gt;2&lt;/sup&gt; for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R &lt;sup&gt;2&lt;/sup&gt; for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with &gt;95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence