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Objectives: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine., Methods: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled. A retrospective analysis of official medical records was accomplished to collect clinical data regarding NPAE occurrence and severity. Univariate statistic and statistical model based on survival analyses were performed., Key Findings: One hundred sixty-two patients were included, of these seventy-seven (47.5%) had NPAE reported, such as dizziness (more frequent), depression and insomnia. Univariate statistical analysis demonstrated that the combined use of efavirenz with zidovudine increased the NPAE risk (OR: 2.5; P-value: 0.008), mainly dizziness risk (OR: 3.5; P-value: 0.009) and survival analysis showed that such combination is associated with dizziness occurrence faster (HR: 2.9; P-value: 0.02)., Conclusions: The results may contribute to clarify the dizziness occurrence dynamics in therapy with efavirenz and zidovudine by identifying susceptibilities and assisting in the choice of combined antiretroviral therapy., (© 2020 Royal Pharmaceutical Society.)

Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated., Objective: To identify predictive genetic markers of immune response to ART., Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure., Results: Male patients were overrepresented in non-responder group (p=0.01). Non-responders also started with lower absolute CD4+ T cell counts (p<0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p=0.04), rs1128503 (ABCB1) A allele (p=0.03) and rs707265 (CYP2B6) A allele (p=0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p=0.004) and rs4646437 (CYP3A4) A allele (p=0.04)., Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Host restriction factors are cellular proteins able to diminish or block viral replication in a cell-specific way., Objective and Method: We evaluated the distribution of single nucleotide polymorphisms (SNPs) in APOBEC3G (rs3736685, rs2294367) and CUL5 (rs7117111, rs7103534, rs11212495) genes, among 264 HIV-1 infected (HIV-1+) and 259 unexposed- uninfected individuals from Northeast Brazil, looking for a possible association with susceptibility to HIV-1 infection, viral load during treatment, CD4+ T cell count and therapeutic success of the antiretroviral treatment., Results: The rs11212495 CUL5 G allele and the CUL5 rs7103534-rs7117111 CG haplotype were more frequent among unexposed-uninfected than in HIV-1+ individuals, suggesting an association with a lower HIV-1 infection susceptibility. The APOBEC3G rs2294367 G/C genotype correlated with delayed viral load suppression. Our results showed a great heterogeneity in relation to the literature findings, possibly due to ethnic differences among the studied populations, sample size used in the studies and, also, to the type of controls, i.e. in our study used unexposed-uninfected rather than exposed-uninfected individuals (rare and considered gold standard for susceptibility studies)., Conclusion: Our findings report genetic variants possibly associated with susceptibility to HIV-1 infection (CUL5 rs11212495, rs7103534, rs7117111) and partial viral load control (APOBEC3G rs2294367). Replica studies performed on higher number of subjects are envisaged to confirm our results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to influence the HIV-1 replication and disease progression., Objective and Method: We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321) and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1-infected and 223 unexposed-uninfected individuals from Northeast Brazil and their relation to HIV-1 infection, CD4 T cells count and viral load pre-treatment., Results: HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four possible haplotypes. Our results showed that HLA-C, ZNRD1 and ZNRD1-AS1 SNPs as well as HLA-C haplotypes frequencies were not significantly different between HIV-1-infected and unexposed-uninfected individuals. In addition, we analyzed HLA-C and ZNRD-1 and ZNRD1-AS1 SNPs considering CD4+ T cell counts and viral load before the antiretroviral treatment. Individuals carrying HLA-C rs9264942 TT genotype showed a significant increased level of HIV-1 viral load pre-treatment, in comparison with individuals carrying the CC genotype (p-value = 0.0092). Finally, we stratified our findings according to CCR5Δ32 allele presence along with the studied SNPs: no statistically significant influence over viral load pre-treatment has been found., Conclusion: The association between HLA-C rs9264942 SNP and viral load prior treatment in an admixed population from North East Brazil was in agreement with findings from previous studies obtained on different ethnic groups; however more studies should be conducted in order to clarify how HLA-C impair the HIV-1 replication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies., Competing Interests: The authors declare no conflict of interest.

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.