scholarly journals Both human immunodeficiency virus–infected and human immunodeficiency virus–exposed, uninfected children living in Brazil, Argentina, and Mexico have similar rates of low concentrations of retinol, β-carotene, and vitamin E

2009 ◽  
Vol 29 (10) ◽  
pp. 716-722 ◽  
Author(s):  
Jacqueline P. Monteiro ◽  
Laura Freimanis-Hance ◽  
Lidiane B. Faria ◽  
Marisa M. Mussi-Pinhata ◽  
James Korelitz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vitamin E ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected ◽  
Β Carotene

DEVELOPMENT OF APPROACHES FOR DETECTION OF GENOME-INTEGRATED PROVIRAL DNA OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV-1) IN ULTRA LOW CONCENTRATIONS USING THE CRISPR/CAS SYSTEM

2020 ◽  
Author(s):  
M.A. Tyumentseva ◽  
◽  
A.I. Tyumentsev ◽  
V.G. Akimkin ◽  
◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Health Monitoring ◽  
Biological Samples ◽  
Proviral Dna ◽  
Guide Rnas ◽  
Ribonucleoprotein Complexes ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Hiv 1

For the effective functioning of supervisory and health monitoring services, it is necessary to introduce modern molecular technologies into their practice. Therefore, the task of developing new effective methods for detecting pathogen, for example HIV, based on CRISPR/CAS genome editing systems, remains urgent. In the present work, guide RNAs and specific oligonucleotides were developed for preliminary amplification of highly conserved regions of the HIV-1 genome. The developed guide RNAs make it possible to detect single copies of HIV-1 proviral DNA in vitro as part of CRISPR/CAS ribonucleoprotein complexes in biological samples after preliminary amplification.

scholarly journals A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus–Exposed Uninfected Infants

2020 ◽  
Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Adverse Events ◽  
Controlled Trial ◽  
Preventive Therapy ◽  
Infection Prevalence ◽  
Mycobacterium Tuberculosis Infection ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

Abstract Background Human immunodeficiency virus (HIV)–exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. Methods We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). Results Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24–1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22–1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. Conclusions Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. Clinical Trials Registration NCT02613169.

scholarly journals Effects of the Translocation Status of Human Immunodeficiency Virus Type 1 Reverse Transcriptase on the Efficiency of Excision of Tenofovir

2007 ◽  
Vol 51 (8) ◽  
pp. 2911-2919 ◽  
Author(s):  
Bruno Marchand ◽  
Kirsten L. White ◽  
John K. Ly ◽  
Nicolas A. Margot ◽  
Ruth Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Complex Formation ◽  
Reverse Transcriptase ◽  
High Rate ◽  
Human Immunodeficiency Virus Replication ◽  
Degree Of Protection ◽  
Cellular Environment ◽  
Dead End ◽  
Low Concentrations ◽  
Immunodeficiency Virus

ABSTRACT The ATP-dependent phosphorolytic excision of nucleoside analogue reverse transcriptase inhibitors can diminish their inhibitory effects on human immunodeficiency virus replication. Previous studies have shown that excision can occur only when the reverse transcriptase complex exists in its pretranslocational state. Binding of the next complementary nucleotide causes the formation of a stable dead-end complex in the posttranslocational state, which blocks the excision reaction. To provide mechanistic insight into the excision of the acyclic phosphonate nucleotide analog tenofovir, we compared the efficiencies of the reaction in response to changes in the translocation status of the enzyme. We found that rates of excision of tenofovir with wild-type reverse transcriptase can be as high as those seen with 3′-azido-3′-deoxythymidine monophosphate (AZT-MP). Thymidine-associated mutations, which confer >100-fold and 3-fold decreased susceptibility to AZT and tenofovir, respectively, caused substantial increases in the efficiency of excision of both inhibitors. However, in contrast to the case for AZT-MP, the removal of tenofovir was highly sensitive to dead-end complex formation. Site-specific footprinting experiments revealed that complexes with AZT-terminated primers exist predominantly pretranslocation. In contrast, complexes with tenofovir-terminated primers are seen in both configurations. Low concentrations of the next nucleotide are sufficient to trap the complex posttranslocation despite the flexible, acyclic character of the compound. Thus, the relatively high rate of excision of tenofovir is partially neutralized by the facile switch to the posttranslocational state and by dead-end complex formation, which provides a degree of protection from excision in the cellular environment.

scholarly journals Age-Related Changes in Expression of CXCR4 and CCR5 on Peripheral Blood Leukocytes from Uninfected Infants Born to Human Immunodeficiency Virus Type 1-Infected Mothers

2004 ◽  
Vol 11 (1) ◽  
pp. 229-234 ◽  
Author(s):  
Sharon Shalekoff ◽  
Glenda E. Gray ◽  
Caroline T. Tiemessen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cord Blood ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Cross Sectional ◽  
Age Related ◽  
Immunodeficiency Virus ◽  
Sectional Analysis ◽  
Exposed Uninfected

ABSTRACT Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected infants revealed high proportions of CXCR4-expressing cells in their cord blood, which declined at 4.5 months and increased between 9 and 15 months to levels approaching those of uninfected adults. Proportions of CCR5-expressing cells, however, were very low in cord blood and subsequently increased with age.

scholarly journals Tumor necrosis factor-dependent production of human immunodeficiency virus 1 in chronically infected HL-60 cells

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2742-2748 ◽  
Author(s):  
K Kitano ◽  
CI Rivas ◽  
GC Baldwin ◽  
JC Vera ◽  
DW Golde
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Virus Production ◽  
Viral Production ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Lag Period ◽  
Low Levels ◽  
Necrosis Factor

Abstract Tumor necrosis factor (TNF) may play a central role in proviral activation and release from latency in cells infected with the human immunodeficiency virus (HIV). We studied viral production and its relation to TNF in a HL-60 cell line (J22-HL-60) infected with a monocytotropic strain of HIV-1JR-FL. Viral production was stimulated to similar levels by TNF, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Production of the virus was not suppressed by 3′-azido-3′-deoxythymidine (AZT), indicating that viral production was not caused by superinfection. Low concentrations of TNF (0.1 ng/mL) induced viral production with a short lag period of 8 hours, and this proviral activation was specifically suppressed by anti- TNF antibodies. However, induction of virus production by 1,25(OH)2D3 showed an extended lag period of 2 to 3 days. The effect of 1,25(OH)2D3 on virus production was also blocked by anti-TNF antibodies, which suggests the direct participation of TNF in this process. TNF accumulated in the culture supernatant of cells stimulated with 1,25(OH)2D3 with a kinetics consistent with its involvement in the action of 1,25(OH)2D3 on viral production. The J22-HL-60 cell line produced low levels of virus when cultured in the absence of an external stimulus; however, this basal viral production was suppressed greater than 80% in the presence of anti-TNF antibodies. Corresponding low levels of TNF were detected in the culture supernatants. Viral production decreased slowly with increasing passage of the cells, and no virus was detected in the supernatants of cells maintained in culture for several months. Concomitantly, TNF was no longer detected in the supernatant of these cells, which suggests that endogenous autocrine production of TNF drives viral production in the unstimulated cells. However, viral production was stimulated in these cells by low concentrations (0.1 ng/mL) of added TNF. These results argue for a central role for TNF in HIV proviral activation in chronically infected myeloid cells.

scholarly journals Sensitivity of human immunodeficiency virus infection to various α, β and γ chemokines

1999 ◽  
Vol 80 (9) ◽  
pp. 2369-2373 ◽  
Author(s):  
Giampaolo Greco ◽  
Carl Mackewicz ◽  
Jay A. Levy
Keyword(s):  
Cell Culture ◽  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Therapeutic Strategies ◽  
Hiv Replication ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Large Panel ◽  
High Concentrations ◽  
Anti Hiv

Examination of a large panel of chemokines indicates that in addition to RANTES, MIP-1α and MIP-1β, the β-chemokine MCP-2 and, to a lesser extent, the γ-chemokine lymphotactin also show anti-human immunodeficiency virus (HIV) activity in cell culture. The amount of chemokine needed to suppress HIV replication by ≤50% was generally greater (≤250 ng/ml) than that required for inhibition of virus infection by RANTES, MIP-1α and MIP-1β. The β-chemokine MCP-3 was found to enhance the replication of both non-syncytium-inducing (NSI) and syncytium-inducing (SI) viruses at high concentrations (0·5–5 μg/ml). In contrast to a previous report, macrophage-derived chemokine was not found to inhibit HIV replication of either NSI or SI viruses, but at low concentrations enhanced NSI virus replication. When small amounts of RANTES or MCP-2 were added together with high concentrations of non-inhibitory chemokines, the anti-HIV effects were countered. Information on chemokines that affect HIV infection could be useful for future therapeutic strategies.

scholarly journals Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants

2019 ◽  
Vol 71 (11) ◽  
pp. 2858-2868 ◽  
Author(s):  
Alaric W D’Souza ◽  
Eshia Moodley-Govender ◽  
Bertram Berla ◽  
Tejas Kelkar ◽  
Bin Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Gut Microbiome ◽  
Cotrimoxazole Prophylaxis ◽  
Β Diversity ◽  
Α Diversity ◽  
Immunodeficiency Virus ◽  
Functional Pathway ◽  
Exposed Uninfected

Abstract Background Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. Methods We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. Results Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. Conclusions Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance.

scholarly journals Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus–infected and Exposed, Uninfected Youth

2019 ◽  
Vol 69 (7) ◽  
pp. 1183-1191 ◽  
Author(s):  
Anna-Barbara Moscicki ◽  
Brad Karalius ◽  
Katherine Tassiopoulos ◽  
Tzy-Jyun Yao ◽  
Denise L Jacobson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cohort Study ◽  
Human Papillomavirus ◽  
Pediatric Hiv ◽  
Quadrivalent Vaccine ◽  
Sexually Active ◽  
Abnormal Cytology ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Exposed Uninfected

AbstractBackgroundPersons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth.MethodsThis is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts.ResultsSeroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively.ConclusionAntibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.

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