scholarly journals Postnatal Cytomegalovirus Exposure in Infants of Antiretroviral-Treated and Untreated HIV-Infected Mothers

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sarah A. Meyer ◽  
Daniel J. Westreich ◽  
Emily Patel ◽  
Elizabeth P. Ehlinger ◽  
Linda Kalilani ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Postnatal Growth ◽  
Hiv Exposed Infants ◽  
Breastfed Infants ◽  
Postnatal Transmission ◽  
Growth Faltering ◽  
Hiv Exposed ◽  
The Impact ◽  
The Relationship ◽  
Hiv 1

HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4–6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log10rise CMV load per log10rise HIV-1 RNA load, 95% CI 0.13–0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (−0.53, 95% CI: −0.96, −0.10) and weight-for-age (−0.40, 95% CI: −0.67, −0.13)Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

scholarly journals Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Prats ◽  
Ignacio Martínez-Zalacaín ◽  
Beatriz Mothe ◽  
Eugènia Negredo ◽  
Núria Pérez-Álvarez ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Integrase Inhibitor ◽  
Strand Transfer ◽  
Cognitive Differences ◽  
Integrase Strand Transfer Inhibitors ◽  
Initiation Of Therapy ◽  
Main Component ◽  
Living With Hiv ◽  
The Impact ◽  
Hiv 1

AbstractIntegrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

scholarly journals Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

2021 ◽  
Vol 17 (6) ◽  
pp. e1009686
Author(s):  
Taina T. Immonen ◽  
Christine M. Fennessey ◽  
Leslie Lipkey ◽  
Abigail Thorpe ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Rhesus Macaques ◽  
Treatment Strategies ◽  
Viral Reservoir ◽  
Virus Population ◽  
Analytical Treatment ◽  
Treatment Interruptions ◽  
The Impact ◽  
Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

scholarly journals Impact of the Umoyo mother-infant pair model on HIV-positive mothers’ social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT Care: Evidence from a cluster randomised control trial in Zambia

2019 ◽  
Author(s):  
Sydney Chauwa Phiri ◽  
Sandra Mudhune ◽  
Margaret L Prust ◽  
Prudence Haimbe ◽  
Hilda Shakwelele ◽  
...  
Keyword(s):  
Public Health ◽  
Social Support ◽  
Health System ◽  
T Test ◽  
Perceived Stigma ◽  
Hiv Exposed Infants ◽  
Pair Model ◽  
Hiv Exposed ◽  
The Impact ◽  
Infant Pair

Abstract Background Public health systems in resource-constrained settings have a critical role to play in the elimination of HIV transmission but are often financially constrained. This study is an evaluation of a mother-infant-pair model called “Umoyo”, which was designed to be low cost and scalable in a public health system. Facilities with the Umoyo model dedicate a clinic day to provide services to only HIV-exposed-infants (HEIs) and their mothers. Such models are in operation with reported success in Zambia but have not been rigorously tested. This work establishes whether the Umoyo model would improve 12-month retention of HEIs. Methods A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate the impact on 12-month retention of HEIs in care. These facilities were offering prevention of mother to child transmission (PMTCT) services and supported by the same implementing partner. Randomization was achieved by use of the covariate constrained optimization technique. Secondary outcomes included the impact of Umoyo clinics on social support and perceived HIV stigma among mothers. For each of the outcomes, a difference-in-difference analysis was conducted at the facility level using the unweighted t-test. Results From 13 control (12-month retention at endline: 45%) and 11 intervention facilities (12-month retention at endline: 33%), it was found that Umoyo clinics had no impact on 12-month retention of HEIs in the t-test (-11%; 99% CI: -40.1%, 17.2%). Regarding social support and stigma, the un-weighted t-test showed no impact though sensitivity tests showed that Umoyo had an impact on increasing social support (0.31; 99% CI: 0.08, 0.54) and reducing perceived stigma from health care workers (-0.27: 99% CI: -0.46, -0.08). Conclusion The Umoyo approach of having a dedicated clinic day for HEIs and their mothers did not improve retention of HEIs though there are indications that it can increase social support among mothers and reduce stigma. Without further support to the underlying health system, based on the evidence generated through this evaluation, the Umoyo clinic day approach on its own is not considered an effective intervention to increase retention of HIV-exposed infants.

scholarly journals Safety and Efficacy of Starting Antiretroviral Therapy in the First Week of Life

2020 ◽  
Author(s):  
Kenneth Maswabi ◽  
Gbolahan Ajibola ◽  
Kara Bennett ◽  
Edmund V Capparelli ◽  
Patrick Jean-Philippe ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Safety And Efficacy ◽  
Hiv Rna ◽  
Early Infant ◽  
Immunodeficiency Virus ◽  
Trough Concentrations ◽  
Hiv Exposed ◽  
Hiv 1

Abstract Background Early antiretroviral therapy (ART) is recommended for infants with human immunodeficiency virus (HIV) infection. However, few antiretroviral options are available for neonates. Methods The Early Infant Treatment Study in Botswana tested HIV-exposed infants within 96 hours of birth, and HIV-infected infants started nevirapine (NVP) 6 mg/kg twice daily, zidovudine (ZDV), and lamivudine (3TC) at age &lt; 7 days. NVP trough concentrations were tested at 1 and 2 weeks. NVP was switched to ritonavir-boosted lopinavir (LPV/r) at week 2, 3, 4, or 5 according to delivery gestational age. Results Forty HIV-infected infants started ART at median age 2 days (range, 1–5 days). NVP trough concentrations were highly variable and below therapeutic target (3000 ng/mL) for 50% of 2-week measurements; concentrations did not correlate with viral decline at weeks 2, 4, or 12. Two deaths unrelated to ART occurred through 24 weeks. Only 1 unscheduled treatment modification was required. Within 4 weeks of transition to LPV/r, 9 (22.5%) had transient HIV RNA increases, likely due to poor LPV/r palatability. At 12 weeks, 22 (55%) of 40 were &lt;40 copies/mL (93% &lt;400 copies/mL); by 24 weeks, 27 of 38 (71%) were &lt; 40 copies/mL (84% &lt; 400 copies/mL). HIV-1 RNA response at 12 and 24 weeks did not differ by baseline HIV RNA or other factors. Conclusions NVP/ZDV/3TC started in the first week of life was safe and effective, even when trough NVP levels were below target. Transient viral increases occurred following transition to LPV/r, but by 12 and 24 weeks most children achieved and maintained viral suppression. Clinical Trials Registration U01AII4235.

scholarly journals Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

2018 ◽  
Vol 69 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Sharon A Riddler ◽  
Jennifer E Balkus ◽  
Urvi M Parikh ◽  
John W Mellors ◽  
Carolyne Akello ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Virologic Failure ◽  
Vaginal Ring ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Cell Counts ◽  
The Impact ◽  
Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

Sign in / Sign up

Export Citation Format

Share Document