Mckaylindgren3662
Early infant diagnosis of HIV (EID) improves child survival through earlier initiation of antiretroviral therapy (ART). In many settings, ART initiation is hindered by delays in testing performed in centralized labs. Point-of-care (PoC) platforms offer opportunities to improve the timeliness of ART initiation.
We used a mathematical model to estimate the costs and performance of on-site PoC testing using three platforms (m-PIMA, GeneXpert IV, and GeneXpert Edge) compared with the standard of care (SoC). Primary outcomes included ART initiation within 60 days of sample collection, HIV-related mortality before ART initiation, and incremental cost-effectiveness ratios (ICERs).
PoC testing significantly increased ART initiation within 60 days (from 19% with SoC to 82-84% with PoC) and decreased HIV-related mortality (from 23% with SoC to 5% with PoC). ART initiation and mortality were similar across PoC platforms. When only used for EID and with high coverage of prevention of mother-to-child transmission (PMTCT) programs, ICERs for PoC testing compared with the SoC ranged from $430 to $1097 per additional infant on ART within 60 days and from $1527 to $3888 per death averted. Bromopyruvic clinical trial PoC-based testing was more cost-effective in settings with lower PMTCT coverage, greater delays in the SoC, and when PoC instruments could be integrated with other disease programs.
Our findings illustrate that PoC platforms can dramatically improve the timeliness of EID and linkage to HIV care. The cost-effectiveness of PoC platforms depends on the cost of PoC testing, existing access to diagnostic testing, and the ability to integrate PoC testing with non-EID programs.
Our findings illustrate that PoC platforms can dramatically improve the timeliness of EID and linkage to HIV care. The cost-effectiveness of PoC platforms depends on the cost of PoC testing, existing access to diagnostic testing, and the ability to integrate PoC testing with non-EID programs.
The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS).
We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020.
Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two.
Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.
Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.
HIV-1 pretreatment drug resistance (PDR) is a global concern. Our aim was to evaluate high-throughput sequencing (HTS) for HIV-1 resistance testing and describe PDR in Sweden, where 75% of diagnosed individuals are foreign-born.
Cross-sectional study.
Individuals entering HIV-1 care in Sweden 2017 to March 2019 (n = 400) were included if a viremic sample was available (n = 220). HTS was performed using an in-house assay. Drug resistance mutations (DRMs) (based on Stanford HIV DB vs. 8.7) at levels 1-5%, 5-19% and at least 20% of the viral population were described. Results from HTS and routine Sanger sequencing were compared.
HTS was successful in 88% of patients, 92% when viral load was at least 1000 copies/ml. DRMs at any level in protease and/or reverse transcriptase were detected in 95 individuals (49%), whereas DRMs at least 20% in 35 (18%) individuals. DRMs at least 20% correlated well to findings in routine Sanger sequencing. Protease/reverse transcriptase (PR/RT) DRMs at least 20% were predicted by treatment exposure; adjusted OR 9.28 (95% CI 2.24-38.43; P = 0.002) and origin in Asia; adjusted OR 20.65 (95% CI 1.66-256.24; P = 0.02). Nonnucleoside reverse transcriptase inhibitor (NNRTI) DRMs at least 20% were common (16%) and over-represented in individuals originating from sub-Saharan Africa or Asia. Low-level integrase strand transfer inhibitor (INSTI) DRMs less than 20% were detected in 15 individuals (8%) with no association with INSTI exposure.
Our HTS can efficiently detect PDR and findings of DRMs at least 20% compare well to routine Sanger sequencing. The high prevalence of PDR was because of NNRTI DRMs and associated with migration from areas with emerging PDR.
Our HTS can efficiently detect PDR and findings of DRMs at least 20% compare well to routine Sanger sequencing. The high prevalence of PDR was because of NNRTI DRMs and associated with migration from areas with emerging PDR.
Osteopenia is frequent in HIV-infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis.
We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a three-drug regimen, and Atazanavir, which was widely utilized in the past.
We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, whereas Darunavir exerts no effect.
Atazanavir and Dolutegravir impair osteogenesis. It is essential to diagnose impaired osteogenesis early and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients, putting it in the context of a correct antiretroviral combination.
Atazanavir and Dolutegravir impair osteogenesis. It is essential to diagnose impaired osteogenesis early and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients, putting it in the context of a correct antiretroviral combination.