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Supplemental Digital Content is Available in the Text. Background: Despite effective antiretroviral therapy (ART), milder forms of HIV-associated neurocognitive disorders remain prevalent and are characterized by neuroinflammation, synaptic dysfunction, and neuronal loss. Methods: We explore associations between neurocognitive impairment in HIV+ Indonesians and 17 polymorphisms in adjacent genes involved in inflammation and neuronal growth/repair pathways, P2X4R and CAMKK2. HIV+ Indonesians (n = 59) who had received ART for 12 months were assessed to derive Z-scores for the attention, fluency, memory, executive, and motor speed domains relative to local control subjects. These were used to determine total cognitive scores. Results: No alleles of P2X4R displayed significant associations with neurocognition in bivariate or multivariable analyses. In CAMKK2 , rs2686344 influenced total cognitive scores in bivariate analyses (P = 0.04). Multivariable linear regression modeling independently associated rs2686344 with higher executive function Z-scores (P = 0.05) after adjusting for CD4 T-cell counts (adjusted R2 = 0.103, model P = 0.034), whereas rs1653588 associated with lower and rs1718120 (P = 0.05) with higher fluency Z-scores (P = 0.05) after adjusting for education and log10 HIV RNA copies/mL (adjusted R2 = 0.268, model P = 0.001). Conclusions: Polymorphisms in CAMKK2 may influence neurocognitive outcomes in specific domains in HIV+ Indonesians receiving ART for 12 months. [ABSTRACT FROM AUTHOR]

Background: Active infections with cytomegalovirus (CMV) increase NK cell expression of the inhibitory receptor LIR-1 and the activating receptor NKG2C in transplant recipients. However, the effects of CMV on NK cells are different in HIV patients stable on antiretroviral therapy (ART) and have not been analyzed in young HIV patients beginning ART. Methodology: We followed a cohort of 78 Indonesian HIV patients beginning ART. CMV antibodies were measured in plasma before ART (baseline), and after 1, 3, 6, and 12 months. CMV DNA was sought in blood granulocytes at baseline by quantitative PCR assay and a deletion in the NKG2C gene was identified by PCR. NK cell profiles were monitored by flow cytometry in 19 patients stratified by the presence of CMV DNA. Healthy controls (n = 17) were assessed once. Results: All 78 patients were CMV seropositive and 41 had detectable CMV DNA. CMV DNA+ patients had higher proportions of total NK cells and CD16+ NK cells at baseline, but similar expression of LIR-1 and NKp30 on NK cells on ART. However, levels of CMV antibody were inversely related to median LIR-1 expression on NK cells. A dramatic elevation in cells expressing NKG2C was restricted to CMV DNA+ patients heterozygous for the NKG2C deletion. Patients with High NKG2C expression had lower levels of CMV antibodies. Conclusion: A subpopulation of NK cells expressing NKG2C was induced by CMV replication in HIV patients heterozygous for a deletion in this gene. Individuals with an abundant NKG2C+ and LIR-1+ NK cells displayed lower levels of CMV reactive antibody. [ABSTRACT FROM AUTHOR]

Highlights • Vitamin D level was low in Indonesian MS and NMO patients. • No significant association between serum vitamin D 25(OH) level and disease severity in MS and NMO patients. • Low level of serum vitamin D should be anticipate in MS or NMO patients who received corticosteroid treatment. Abstract Background Vitamin D deficiency is commonly found in multiple sclerosis (MS) and Neuromyelitis Optic (NMO) patients and can impair the immunological status. As a tropical country, Indonesia has a lot of sunshine throughout the year as a source of vitamin D. The aim of this study was to evaluate and compare the serum vitamin D-25(OH) level in Indonesian MS and NMO patients to healthy individuals. Methods A cross-sectional study was conducted in Dr. Cipto Mangunkusumo General Hospital Jakarta from November 2016 to May 2017. Forty-eight patients (29 MS and 19 NMO) and 33 healthy controls were enrolled. We assessed the dietary recall, vitamin D supplementation, sunshine exposure, medication, annual relapse rate, and Expanded Disability Status Scale (EDSS). Vitamin D level was measured using direct competitive chemiluminescence immunoassay. Results Vitamin D deficiency was found in 48.4% of MS and 56.2% of NMO patients. The serum vitamin D level in MS and NMO groups was not significantly different from the healthy controls. Vitamin D level was not associated with EDSS and the annual relapse rate. Positive significant correlation was observed between sunshine exposure and vitamin D level in healthy control, but not evident in MS and NMO groups. MS and NMO subjects who still treated with corticosteroid had lower vitamin D level. Conclusion Vitamin D deficiency is commonly found in Indonesian MS and NMO patients, but not associated with EDSS and annual relapse rate. Despite living in a country with adequate sunshine exposure, the physician should anticipate low serum vitamin D level, especially in MS or NMO patients who received corticosteroid. [ABSTRACT FROM AUTHOR]

Altered T cell profiles have been linked with metrics of persistent cytomegalovirus (CMV) infections in healthy aging and older HIV patients stable on antiretroviral therapy (ART). In this study, we use CMV DNA to identify active infections, and levels of CMV-reactive antibody to assess the persistent burden of CMV in a longitudinal study of 78 young adult patients beginning ART in Jakarta, Indonesia, with <200 CD4 T cells/ μ L. CMV antibodies, inflammatory markers (C-reactive protein [CRP], soluble interferon- α / β receptor) and T cell phenotypes were assessed before ART (V0) and after 1, 3, 6, and 12 months (V1–V12). CMV DNA was detected in 41 patients (52%) at V0, irrespective of CD4 T cell counts, gender, age, or plasma HIV RNA. CMV DNA+ patients had higher levels of antibody reactive with CMV Immediate Early 1 (IE-1) at V0 and V12 ( p  = 0.04), and with CMV lysate at V12 ( p  = 0.01). Detectable CMV DNA did not align with inflammatory markers, but associated with lower CD4/CD8 ratios until V3. CMV antibody levels correlated inversely with proportions of naive CD4 and CD8 T cells, and directly with proportions of CD57+ and activated memory T cells (CD3+ CD45RA−) after 3–12 months on ART. Overall, active CMV replication is common in HIV patients beginning ART in Indonesia and associates with low CD4/CD8 ratios. Elevated levels of CMV-reactive antibody measured on ART also mark a depletion of naive T cells, accumulation of memory T cells, and may be a stable metric of the burden of CMV. [ABSTRACT FROM AUTHOR]

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine influenced by single nucleotide polymorphisms (SNP) located in upstream regulatory regions. Here we address the effects of five SNP (rs1518111, rs3021094, rs3024491, rs1800872 and rs1800871) on CD4 T-cell counts in Indonesian HIV patients assessed before ART and over 12 months on treatment. Heterozygosity at rs1518111 or rs1800872 associated with low CD4 T-cell counts at all time points. Both alleles were carried in two haplotypes. Haplotype 2 11 2 2 (present in 30% of participants) associated with low CD4 T-cell counts, whereas 2 12 2 2 (in 6% of participants) did not. Hence untyped SNP(s) tagged by 2 11 2 2 may depress CD4 T-cell counts. The association with heterozygosity suggests synergy with an allele from a haplotype lacking rs1518111 and/or rs1800872. [ABSTRACT FROM AUTHOR]