Effect of TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor alpha (TNF-α) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.</p> <p>Methods</p> <p>We aimed to determine whether carriage of the <it>TNF-α-238G>A, -308G>A </it>and <it>-863 C>A </it>gene promoter single nucleotide polymorphisms (SNP) and the <it>CCR5Δ32 </it>variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration). <it>TNF-α </it>SNP and the <it>CCR5Δ32 </it>allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the χ 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.</p> <p>Results</p> <p>The distribution of <it>TNF-α-238G>A, -308G>A </it>and <it>-863 C>A </it>genetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals: <it>-238G>A</it>, p = 0.7 and p = 0.3; <it>-308G>A</it>, p = 0.05 and p = 0.07; <it>-863 C>A</it>, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the three <it>TNF-α </it>genetic variants assessed was non-significantly different between TP and LTNP: <it>-238G>A</it>, p = 0.35 and p = 0.7; <it>-308G>A</it>, p = 0.7 and p = 0.6: <it>-863 C>A</it>, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset indicated that the <it>TNF-α-238A </it>variant allele was significantly overrepresented in patients who spontaneously controlled plasma viremia compared with those who had a detectable plasma viral load (genotype comparisons, p = 0.02; allele comparisons, p = 0.03). The <it>CCR5Δ32 </it>distribution was non-significantly different in HIV-1-infected patients with respect to the uninfected population (p = 0.15 and p = 0.2 for genotype and allele comparisons, respectively) and in LTNP vs TP (p = 0.4 and p = 0.5 for genotype and allele comparisons, respectively).</p> <p>Conclusions</p> <p>In our cohort of Caucasian Spaniards, <it>TNF-α </it>genetic variants could be involved in the vulnerability to HIV-1 infection. <it>TNF-α </it>genetic variants were unrelated to disease progression in infected subjects. The <it>-238G>A </it>SNP may modulate the control of viremia in LTNP. Carriage of the <it>CCR5Δ32 </it>variant allele had no effect on the risk of infection and disease progression.</p

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

Lack of association of SDF-1 3'A variant allele with long-term nonprogressive HIV-1 infection is extended beyond 16 years

We studied the frequency of the SDF-1 3'A allelic variant (801G-->A) in a cohort of white Spaniards made up of (1) HIV-1-infected long-term nonprogressors (LTNPs) older than 16 years of age (n = 57), (2) HIV-1-infected usual progressors (UPs; n = 107), and (3) a group of healthy controls (n = 100). The mutant SDF-1 3'A allele was observed in 28% of LTNPs, 19% of UPs, and 26% of healthy controls (P = not significant). Homozygosity for the 3'A mutation was detected in 7%, 4%, and 3% of LTNPs, UPs, and healthy controls, respectively (P = not significant). Polymorphism at the SDF-1 locus is not associated with LTNP disease of longer than 16 years in Spanish HIV-1-infected patients. This effect is independent of the CCR5Delta32 allele

Persistence of antiretroviral treatment in emtricitabine/tenofovir (FTC/TDF) users vs other NRTI in ART-na&#x00EF;ve patients&#x003E;50 years: TRIP study

The major antiretroviral guidelines recommend starting ART in patients&#x003E;50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in na&#x00EF;ve patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV-infected patients&#x003E;50 y at the time they began the first cART regimen (January 1, 2006 &#x2013; December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no-TDF). We compared the persistence of treatment in FTC/TDF users vs. no-TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/&#x03BC;l, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no-TDF) (22 with PI, 23 NNRTI). During the follow-up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1.*Adjusted by age, sex, transmission category and baseline CD4 count and viral load. In our study (antiretroviral-na&#x00EF;ve patients&#x003E;50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing

Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an increased frequency of the CX3CR1 249I variant allele

Background and Objectives: The influence of the polymorphisms of the CX3CR1 chemokine receptor gene on the natural history of HIV-1 infection is controversial. This study aimed to determine whether functionally active CX3CR1 genetic variants are associated with long-term nonprogressive infection of > 15 years in HIV-1-infected Spanish patients. Patients and Methods: Two single-nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who were long-term nonprogressors (LTNPs) of > 15 years, 109 HIV-1-infected patients who were usual progressors (UPs), and 102 control subjects. The CCR5Δ32 was also assessed. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by the χ 2 test and the Fisher exact test. Results: The frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35% for healthy controls; the differences between LTNPs and UPs were significant (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The haplotype 249I280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5Δ32. Conclusions: CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected LTNPs of > 15 years. This effect is independent of the presence of the CCR5Δ32 allele