scholarly journals Novel Criteria for Diagnosing Acute and Early HIV Infection in a Multi-National Study of Early Antiretroviral Therapy Initiation

Author(s):  
Trevor A Crowell ◽  
Justin Ritz ◽  
Robert W Coombs ◽  
Lu Zheng ◽  
Joseph J Eron ◽  
...  

Abstract Background Antiretroviral therapy (ART) initiation during acute and early HIV infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of new AEHI diagnostic criteria from a multi-national prospective study of ART initiation during AEHI. Methods ACTG 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any one of six criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Combo Ag/Ab CMIA or GS HIV COMBO Ag/Ab EIA. HIV infection and Fiebig stage were subsequently confirmed by centralized testing. Results From 2017-2019, 195 participants were enrolled with median age 27 (interquartile range 23-39) years. Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, four (2.0%) participants were retrospectively found to have chronic infection, and three (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results. Conclusions Novel AEHI criteria incorporating ARCHITECT S/CO into diagnostic algorithms facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These new criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Qilin Sun ◽  
Lequan Min

This paper studies a modified human immunodeficiency virus (HIV) infection differential equation model with a saturated infection rate. It is proved that if the basic virus reproductive numberR0of the model is less than one, then the infection-free equilibrium point of the model is globally asymptotically stable; ifR0of the model is more than one, then the endemic infection equilibrium point of the model is globally asymptotically stable. Based on the clinical data from HIV drug resistance database of Stanford University, using the proposed model simulates the dynamics of the two groups of patients’ anti-HIV infection treatment. The numerical simulation results are in agreement with the evolutions of the patients’ HIV RNA levels. It can be assumed that if an HIV infected individual’s basic virus reproductive numberR0<1then this person will recover automatically; if an antiretroviral therapy makes an HIV infected individual’sR0<1, this person will be cured eventually; if an antiretroviral therapy fails to suppress an HIV infected individual’s HIV RNA load to be of unpredictable level, the time that the patient’s HIV RNA level has achieved the minimum value may be the starting time that drug resistance has appeared.


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.


2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Emily R. Bowman ◽  
◽  
Manjusha Kulkarni ◽  
Janelle Gabriel ◽  
Xiaokui Mo ◽  
...  

Abstract Background Dyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation. Methods Concentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13). Results Compared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)-containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers. Conclusions HIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes. Trial registration This study is registered with Clinicaltrials.gov (NCT00660972). Registered April 16, 2008.


2019 ◽  
Vol 113 (10) ◽  
pp. 610-616
Author(s):  
Beatrice Dupwa ◽  
Ajay M V Kumar ◽  
Jaya Prasad Tripathy ◽  
Owen Mugurungi ◽  
Kudakwashe C Takarinda ◽  
...  

Abstract Background WHO recommends retesting of HIV-positive patients before starting antiretroviral therapy (ART). There is no evidence on implementation of retesting guidelines from programmatic settings. We aimed to assess implementation of HIV retesting among clients diagnosed HIV-positive in the public health facilities of Harare, Zimbabwe, in June 2017. Methods This cohort study involved analysis of secondary data collected routinely by the programme. Results Of 1729 study participants, 639 (37%) were retested. Misdiagnosis of HIV was found in six (1%) of the patients retested—all were infants retested with DNA-PCR. There was no HIV misdiagnosis among adults. Among those retested, 95% were retested on the same day and two-thirds were tested by a different provider as per national guidelines. Among those retested and found positive, 95% were started on ART, while none of those with negative retest results were started on ART. Of those not retested, about half (51%) were started on ART. The median (IQR) time to ART initiation from diagnosis was 0 (0–1) d. Conclusion The implementation of HIV-retesting policy in Harare was poor. While most HIV retest positives were started on ART, only half non-retested received ART. Future research is needed to understand the reasons for non-retesting and non-initiation of ART among those not retested.


2020 ◽  
pp. 1-9
Author(s):  
Jozefien De Clercq ◽  
Sofie Rutsaert ◽  
Marie-Angélique De Scheerder ◽  
Chris Verhofstede ◽  
Steven Callens ◽  
...  

2012 ◽  
Vol 16 (10) ◽  
pp. 1358-1364 ◽  
Author(s):  
S. Takuva ◽  
D. Westreich ◽  
C. N. Menezes ◽  
L. McNamara ◽  
I. Sanne ◽  
...  

2014 ◽  
Vol 12 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Kaku So-Armah ◽  
Joyce Chang ◽  
Charles Alcorn ◽  
Vincent Re ◽  
Jason Baker ◽  
...  

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S441-S441
Author(s):  
Daniel Smith ◽  
Qianmiao Gao ◽  
Hongyu Miao ◽  
Oswaldo Gutierrez ◽  
Cecilio Martinez ◽  
...  

2015 ◽  
Vol 31 (5) ◽  
pp. 514-518 ◽  
Author(s):  
Nancy F. Crum-Cianflone ◽  
Xun Wang ◽  
Anuradha Ganesan ◽  
Jason Okulicz ◽  
Amy Weintrob ◽  
...  

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
Sara Gianella ◽  
Antoine Chaillon ◽  
Tae-Wook Chun ◽  
Michael C. Sneller ◽  
Caroline Ignacio ◽  
...  

ABSTRACT If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments. Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled therapeutic vaccine clinical trial in people with HIV (PWH) who began antiretroviral therapy (ART) during acute or early infection (ClinicalTrials registration no. NCT01859325). After the week 56 visit (postintervention), all participants interrupted ART. At the first available time points after viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Comprehensive sequence and phylogenetic analyses were performed to evaluate viral population structure, compartmentalization, and viral diversity in blood and seminal plasma. Compared to that in blood, HIV RNA rebound in semen occurred significantly later (median of 66 versus 42 days post-ART interruption, P < 0.01) and reached lower levels (median 164 versus 16,090 copies/ml, P < 0.01). Three of five participants with available sequencing data presented compartmentalized viral rebound between blood and semen in one HIV coding region. Despite early ART initiation, HIV RNA molecular diversity was higher in semen than in blood in all three coding regions for most participants. Higher HIV RNA molecular diversity in the genital tract (compared to that in blood plasma) and evidence of compartmentalization illustrate the distinct evolutionary dynamics between these two compartments after ART interruption. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART. IMPORTANCE To cure HIV, we likely need to target the reservoirs in all anatomic compartments. Here, we used sophisticated statistical and phylogenetic methods to analyze blood and semen samples collected from 12 persons with HIV who began antiretroviral therapy (ART) during very early HIV infection and who interrupted their ART as part of a clinical trial. First, we found that HIV RNA rebound in semen occurred significantly later and reached lower levels than in blood. Second, we found that the virus in semen was genetically different in some participants compared to that in blood. Finally, we found increased HIV RNA molecular diversity in semen compared to that in blood in almost all study participants. These data suggest that the HIV RNA populations emerging from the genital compartment after ART interruption might not be the same as those emerging from blood plasma. Future research should evaluate whether the genital compartment might contribute to viral rebound in some people with HIV (PWH) interrupting ART.


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