Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, ...next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method's performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.
Popliteal artery aneurysm (PAA) is a rare disease with a prevalence of 0.1% to 1%. Within previous years, endovascular repair (ER) of PAAs has been performed more frequently despite the lack of ...high-level evidence compared with open surgical repair (OSR). In 2014, the POPART registry was initiated to validate the current treatment options for PAA repair.
POPART is a multinational multicenter registry of the peri- and postoperative outcomes of ER and OSR for PAAs. Data sets were recorded using the online survey tool SurveyMonkey (available at: https://www.surveymonkey.com/). Regular monitoring and plausibility checks of the data sets are performed to ensure reliability. The aim of the present study was to report the findings from the POPART registry, which includes data from 41 centers.
From June 2014 to August 2019, 794 cases had been recorded in the POPART registry. OSR had been performed in 662 patients and ER in 106 patients; 23 patients had been treated conservatively. Of the 106 patients in the primary ER group, 4 had required conversion to OSR. The ER patients were significantly older (ER, median, 71 years; OSR, median, 67 years; P < .05). No other significant differences were present in the demographic data, comorbidities, or aneurysm morphology between the two groups. Of the 662 patients in the OSR group, 50.3% were symptomatic compared with 29.2% of the 106 patients in the ER group (P < .05). Emergency treatment because of acute ischemia, critical ischemia, or rupture was necessary for 149 patients (22.5%) in the OSR group and 11 patients (10.3%) in the ER group. The most frequent postoperative complications were impaired wound healing (OSR, n = 47 7.1%; ER, n = 3 2.8%; P > .05) and major bleeding (OSR, n = 26 3.9%; ER, n = 3 2.8%; P > .05). The in-hospital length of stay was significantly longer for the OSR group than for the ER group (median, 10 days; range, 3-65 days; vs median, 7 days; range, 1-73 days). The overall patency for the OSR and ER groups after 12 and 24 months was 83.2% and 44.7% (P < .005) and 74.2% and 29.1% (P < .005), respectively. The outcomes with a prosthetic graft vs an autologous vein were significantly poorer in the OSR group (primary patency, 71.4% vs 88.1% at 12 months).
To evaluate new treatment techniques such as ER for PAAs, real-world data are of essential importance. The present analysis of the first results for the POPART registry shows good perioperative results for endovascular treatment of PAA in asymptomatic patients with good outflow vessels. The perioperative complication rate is low and the postoperative hospital stay is shorter than after OSR. However, the patency rates after 12 and 24 months are low in the ER group compared to patients treated with open repair. More follow-up data is required for further interpretation; the completion of the data sets in the registry is ongoing.
Abstract
Background
There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy ...(ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation.
Methods
This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count.
Results
The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200–499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 95% confidence interval, .12–.74; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200–499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio aHR, 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001).
Conclusions
Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200–499 cells/µL.
Clinical Trials Registration
NCT01900977.
There are concerns that people initiating antiretroviral therapy (ART) with high CD4 counts may exhibit reduced HIV virological suppression. In this study, however, participants with CD4 count ≥500 cells/µL had excellent virological outcomes, better than those with lower CD4 counts.
Introduction
Universal HIV testing and treatment aims to identify all people living with HIV and offer them treatment, decreasing the number of individuals with unsuppressed HIV and thus reducing HIV ...transmission. Longitudinal follow‐up of individuals with and without HIV in a cluster‐randomized trial of communities allowed for the examination of community‐ and individual‐level measures of HIV risk and HIV incidence.
Methods
HPTN 071 (PopART) was a three‐arm cluster‐randomized trial conducted between 2013 and 2018 that evaluated the use of two combination HIV prevention strategies implemented at the community level to reduce HIV incidence compared to the standard of care. The trial, conducted in 21 communities in Zambia and South Africa, measured HIV incidence over 36 months in a population cohort of ∼2000 randomly selected adults per community aged 18–44. Multilevel models were used to assess the association between HIV incidence and community‐ and individual‐level socio‐demographic and behavioural risk factors, as well as prevalence of detectable virus (PDV) defined as the estimated proportion of the community with unsuppressed viral load.
Results
Overall HIV incidence was 1.49/100 person‐years. Communities with less financial wealth and communities with more individuals reporting having sex partners outside of the community or two or more sexual partners had higher HIV incidence. PDV at 2 years of study was 6.8% and was strongly associated with HIV incidence: for every 50% relative reduction in community PDV, there was a 49% (95% confidence interval CI: 37%–58%, p < 0.001) relative decrease in HIV incidence. At the individual level; socio‐economic status, AUDIT score, medical male circumcision and certain sexual behaviours were associated with HIV risk.
Conclusions
Using data from the PopART randomized trial, we found several associations of HIV incidence with community‐level measures reflecting the sexual behaviour and socio‐economic make‐up of each community. We also found a strong association between community PDV and HIV incidence supporting the use of PDV as a tool for monitoring progress in controlling the epidemic. Lastly, we found significant individual‐level factors of HIV risk that are generally consistent with previous HIV epidemiological research. These results have the potential to identify high high‐incidence communities, inform structural‐level interventions, and optimize individual‐level interventions for HIV prevention.
Clinical Trial Number
ClinicalTrials.gov number, NCT01900977, HPTN 071 PopArt
To describe our clinical experience of endovascular exclusion of popliteal artery aneurysms using the new self-expandable covered stent SOLARIS® (Scitech Medical, Brazil), and to report its results ...in the context of surgical and endovascular treatment of popliteal artery aneurysms.
Among 20 popliteal artery aneurysms undergoing open or endovascular repair in 2022 and 2023, two patients were successfully treated with the Solaris stentgraft. Both patients had a patent popliteal artery and three run-off vessels. After stentgraft implantation, they received dual antiplatelet therapy for three months and they were followed-up with Duplex scan and clinical evaluation after three months, and every six months thereafter. After three months, one Solaris stentgraft had complete thrombosis and the other ruptured, requiring surgical removal. No complications were observed among the other aneurysms treated with open repair or with the Viabahn® stentgraft.
Endovascular treatment of popliteal aneurysms with the new covered self-expandable stent Solaris resulted in severe complications in the two cases reported, and in worse short-term outcomes than endovascular repair with Viabahn® and open repair. Its off-label use to treat popliteal artery aneurysms should be therefore discouraged.
Introduction
Cross‐sectional incidence testing is used to estimate population‐level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of ...estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross‐sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi‐assay algorithms (MAA) for incidence estimation to that observed in the community‐randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.
Methods
HIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016–2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA‐C: LAg‐Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg‐Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.
Results and discussion
The study consisted of: 15,845 HIV‐negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV‐positive participants at the 2‐year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17–1.53). Estimates of incidence were similar to observed incidence for MAA‐C, 1.26% (95% CI: 1.02–1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97–1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69–1.15, p<0.01).
Conclusions
MAA‐C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.
South Africa is reported to have the highest burden of HIV with an estimated 8.2 million people living with HIV (PLHIV) in 2021- despite adopting the World Health Organisation (WHO) universal HIV ...test and treat (UTT) recommendations in 2016. As of 2021, only an estimated 67% (5.5 million) of all PLHIV were accessing antiretroviral therapy (ART), as per recorded clinic appointments attendance. Studies in sub-Saharan Africa show that people living in low-income households experience multiple livelihood-related barriers to either accessing or adhering to HIV treatment including lack of resources to attend to facilities and food insecurity. We describe the interactions between managing household income and ART adherence for PLHIV in low-income urban and semi-urban settings in the Western Cape, South Africa.
We draw on qualitative data collected as part of the HPTN 071 (PopART) HIV prevention trial (2016 - 2018) to provide a detailed description of the interactions between household income and self-reported ART adherence (including accessing ART and the ability to consistently take ART as prescribed) for PLHIV in the Western Cape, South Africa. We included data from 21 PLHIV (10 men and 11 women aged between 18 and 70 years old) from 13 households. As part of the qualitative component, we submitted an amendment to the ethics to recruit and interview community members across age ranges. We purposefully sampled for diversity in terms of age, gender, and household composition.
We found that the management of household income interacted with people's experiences of accessing and adhering to ART in diverse ways. Participants reported that ART adherence was not a linear process as it was influenced by income stability, changing household composition, and other financial considerations. Participants reported that they did not have a fixed way of managing income and that subsequently caused inconsistency in their ART adherence. Participants reported that they experienced disruptions in ART access and adherence due to competing household priorities. These included difficulties balancing between accessing care and/or going to work, as well as struggling to cover HIV care-related costs above other basic needs.
Our analysis explored links between managing household income and ART adherence practices. We showed that these are complex and change over the course of treatment duration. We argued that mitigating negative impacts of income fluctuation and managing complex trade-offs in households be included in ART adherence support programmes.
Introduction: Population‐wide HIV testing services (HTS) must be delivered in order to achieve universal antiretroviral treatment (ART) coverage. To accurately deliver HTS at such scale, ...non‐facility‐based HIV point‐of‐care testing (HIV‐POCT) is necessary but requires rigorous quality assurance (QA). This study assessed the performance of community‐wide HTS in Zambia and South Africa (SA) as part of the HPTN 071 (PopART) study and explores the impact of quality improvement interventions on HTS performance.
Methods: Between 2014 and 2016, HIV‐POCT was undertaken within households both as part of the randomly selected HPTN 071 research cohort (Population Cohort PC) and as part of the intervention provided by community HIV‐care providers. HIV‐POCT followed national algorithms in both countries. Consenting PC participants provided a venous blood sample in addition to being offered HIV‐POCT. We compared results obtained in the PC using a laboratory‐based gold standard (GS) testing algorithm and HIV‐POCT. Comprehensive QA mechanisms were put in place to support the community‐wide testing. Participants who were identified as having a false negative or false positive HIV rapid test were revisited and offered retesting.
Results: We initially observed poor sensitivity (45–54%, 95% confidence interval CI 31–69) of HIV‐POCT in the PC in SA compared to sensitivity in Zambia for the same time period of 95.8% (95% CI 93–98). In both countries, specificity of HIV‐POCT was >98%. With enhanced QA interventions and adoption of the same HIV‐POCT algorithm, sensitivity in SA improved to a similar level as in Zambia.
Conclusions: This is one of the first reports of HIV‐POCT performance during wide‐scale delivery of HTS compared to a GS laboratory algorithm. HIV‐POCT in a real‐world setting had a lower sensitivity than anticipated. Appropriate choice of HIV‐POCT algorithms, intensive training and supervision, and robust QA mechanisms are necessary to optimize HIV‐POCT test performance when testing is delivered at a community level. HIV‐POCT in clients who did not disclose that they were on ART may have contributed to false negative HIV‐POCT results and should be the topic of future research.
Zusammenfassung
Poplitealarterienaneurysmen (PAA) sind eine seltene Krankheitsentität, jedoch die häufigste Form peripherer arterieller Aneurysmen. Grundsätzlich sollten diese ab einer Größe von mehr ...als 2 cm oder in jedem Fall bei klinischer Symptomatik versorgt werden. Eine elektive Versorgung ist günstiger als eine Notfallversorgung. Die offen-chirurgische PAA-Ausschaltung ist chirurgisch mit Vene oder Kunststoff als Bypassmaterial möglich, jedoch ist Vene, wenn in guter Qualität verfügbar, zu bevorzugen. Abhängig vom anatomischen Situs steht ein dorsaler oder medialer Zugang zur Verfügung. Auch die endovaskuläre PAA-Versorgung nimmt in den letzten Jahren deutlich zu. Jüngste Studien zeigen, dass nach endovaskulärer PAA-Ausschaltung durchaus der offenen Chirurgie gleichwertige Ergebnisse erzielt werden können. Jedoch fehlen dazu bislang prospektive randomisierte klinische Studien.
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