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

Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings