scholarly journals Divergence of delta and beta variants and SARS-CoV-2 evolved in prolonged infection into distinct serological phenotypes

Author(s):  
Sandile Cele ◽  
Farina Karim ◽  
Gila Lustig ◽  
San Emmanuel James ◽  
Tandile Hermanus ◽  
...  

SARS-CoV-2 continues to evolve variants of concern (VOC) which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the delta VOC has been reported to escape beta elicited immunity. Systematic mapping of the serological distance of current and emerging variants will likely guide the design of vaccines which can target all variants. Here we isolated and serologically characterized SARS-CoV-2 which evolved from an ancestral strain in a person with advanced HIV disease and delayed SARS-CoV-2 clearance. This virus showed evolving escape from self antibody neutralization immunity and decreased Pfizer BNT162b2 vaccine neutralization sensitivity. We mapped neutralization of evolved virus and ancestral, beta and delta variant viruses by antibodies elicited by each VOC in SARS-CoV-2 convalescent individuals. Beta virus showed moderate (7-fold) and delta slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, delta virus had stronger escape from beta elicited immunity (12-fold), and beta virus even stronger escape from delta immunity (34-fold). Evolved virus had 9-fold escape from ancestral immunity, 27-fold escape from delta immunity, but was effectively neutralized by beta immunity. We conclude that beta and delta are serologically distant, further than each is from ancestral, and that virus evolved in prolonged infection during advanced HIV disease is serologically close to beta and far from delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes and that vaccines tailored to one variant may become vulnerable to infections with another.

Aids Reviews ◽  
2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Joaquim Burgos ◽  
Esteban Ribera ◽  
Vicenç Falcó

1999 ◽  
Vol 39 (2) ◽  
pp. 146-152 ◽  
Author(s):  
Roberto Manfredi ◽  
Anna Nanetti ◽  
Morena Ferri ◽  
Antonio Mastroianni ◽  
Olga V. Coronado ◽  
...  

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 886-890
Author(s):  
Mark W. Kline ◽  
Courtney V. Fletcher ◽  
Marianne E. Federici ◽  
Alice T. Harris ◽  
Kim D. Evans ◽  
...  

Objectives. To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. Methods. Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 42 cells/µL; range, 8 to 553 cells/µL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. Results. Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4+ lymphocyte counts greater than 50 cells/µL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4+ lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. Conclusions. Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.


2021 ◽  
Vol 2 (3) ◽  
pp. 22-29
Author(s):  
Sylvia T. Echendu ◽  
Ebelechuku F. Ugochukwu ◽  
Kenneth N. Okeke ◽  
Chinyere U. Onubogu ◽  
Joy C. Ebenebe ◽  
...  

Background: The disease burden associated with HIV/AIDS is a key factor in the etiopathogenesis of undernutrition in growing children. This is aggravated by resultant social factors in HIV such as orphaning, low socioeconomic status, food insecurity, and marital status of caregivers. Objectives: The relationship between sociodemographic factors and malnutrition in the background of HIV was evaluated. Methods: A cross-sectional descriptive survey was conducted among under-five HIV positive children in Anambra State, Nigeria. Results: A total of 370 HIV positive under-five children comprising 208(56.2%) males and 162(43.8%) females were recruited. The mean age of the children was 44.5±12.9 months. One hundred and forty-seven (39.7%) were globally undernourished: 15.7.0% (58) underweight (WFA <-2SD), 13.3% (49) wasted (WFH < -2SD), and 27.9% (103) stunted (HFA <-2SD). Males were significantly more stunted than females (p<0.001). 77% (285) were of low socioeconomic class (SEC), 47.3% (175) had advanced HIV disease, and 68.1% (252) had been on HAART for >12 months. 26% (96) were orphans, while 28.6% (106) were cared for by single parents. Being on HAART for >12 months was associated with less undernutrition, while advanced HIV disease seemed to enhance it. Children of low SEC were more likely to be undernourished. Not having been breastfed, introduction of complementary feeds at age 3mo or less, poor food variety and suboptimal feeding frequency increased susceptibility to undernutrition. Orphans were more wasted and stunted than underweight. Single parenthood predisposed to undernutrition. Conclusions: HIV-infected children are vulnerable to malnutrition by virtue of the disease process, further compounded by interwoven social dilemma associated with HIV. It, therefore, behooves the health care provider to ensure a proactive growth monitoring and nutritional support, with prompt treatment of co-morbid debilitating infections. There is also a dire need for public health interventions targeted at single parents of low socioeconomic means.


Digestion ◽  
1993 ◽  
Vol 54 (1) ◽  
pp. 9-14
Author(s):  
Nicola Napoli ◽  
Giorgio Fiore ◽  
Giacomo Fera ◽  
Angela Modugno ◽  
Gianluigi Giannelli ◽  
...  

2001 ◽  
Vol 28 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Ruth Eisenbud ◽  
Susan F. Assmann ◽  
Leslie A. Kalish ◽  
Charles van der Horst ◽  
Ann C. Collier

Author(s):  
Sandile Cele ◽  
Farina Karim ◽  
Gila Lustig ◽  
James Emmanuel San ◽  
Tandile Hermanus ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259073
Author(s):  
Nadine Mayasi Ngongo ◽  
Gilles Darcis ◽  
Hippolyte Situakibanza Nanituna ◽  
Marcel Mbula Mambimbi ◽  
Nathalie Maes ◽  
...  

Background The benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management. This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors. Methods and findings HIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models. A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women. Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively. The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period. The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3–2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64–0.86) (p<0.0001). Conclusion Despite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented.


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