Treatment with integrase inhibitors alters SARS-CoV-2 neutralization levels measured with HIV-based pseudotypes in people living with HIV

The presence of neutralizing antibodies (NAbs) is a major correlate of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thus, different in vitro pseudoviruses-based assays have been described to detect NAbs against SARS-CoV-2. However, the determination of NAbs against SARS-CoV-2 in people living with HIV (PLWH) through HIV-based pseudoparticles could be influenced by cross-neutralization activity or treatment, impeding accurate titration of NAbs. Two assays were compared using replication-defective HIV or VSV-based particles pseudotyped with SARS-CoV-2 spike to measure NAbs in COVID-19-recovered and COVID-19-naïve PLWH. The assay based on HIV-pseudoparticles displayed neutralization activity in all COVID-19-recovered PLWH with a median neutralizing titer 50 (NT50) of 1417.0 (interquartile range [IQR]: 450.3-3284.0), but also in 67% of COVID-19-naïve PLWH (NT50: 631.5, IQR: 16.0-1535.0). Regarding VSV-pseudoparticles system, no neutralization was observed in COVID-19-naïve PLWH as expected, whereas in comparison with HIV-pseudoparticles assay lower neutralization titers were measured in 75% COVID-19-recovered PLWH (NT50: 100.5; IQR: 20.5-1353.0). Treatment with integrase inhibitors was associated with inaccurate increase in neutralization titers when HIV-based pseudoparticles were used. IgG purification and consequent elimination of drugs from samples avoided the interference with retroviral cycle and corrected the lack of specificity observed in HIV-pseudotyped assay. This study shows methodological alternatives based on pseudoviruses systems to determine specific SARS-CoV-2 neutralization titers in PLWH

Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants

<p>Abstract</p> <p>Background</p> <p>Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.</p> <p>Methods</p> <p>The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).</p> <p>Results</p> <p>Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.</p> <p>Conclusion</p> <p>This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.</p

Medicines information and adherence in HIV/AIDS patients

Background: Providing written medicines information is being legislated in an increasing number of countries worldwide, with the patient information leaflet (PIL) being the most widely used method for conveying health information. The impact of providing such information on adherence to therapy is reportedly unpredictable. Therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and related opportunistic infections usually involves polytherapy and complex regimens, both of which are risk factors for non-adherence. The objective of this study was to assess the impact of medicines information on adherence to chronic co-trimoxazole therapy in low-literate HIV/AIDS patients. Methods: Two different PILs were designed for co-trimoxazole tablets and were available in both English and isiXhosa. Participants were randomly allocated to a control group (receiving no PIL), group A (receiving a 'complex PIL') and group B (receiving a 'simple PIL' incorporating pictograms). At the first interview, demographic data were collected and the time, date and day that the participant would take his/her first tablet of the month's course was also documented. In a follow-up interview adherence to therapy was assessed using two methods; self-report and tablet count. Results: The medicines information materials incorporating simple text and pictograms resulted in significantly improved adherence to therapy in the short term, whereas a non-significant increase in adherence was associated with the availability of the more complex information. This was shown by both the self-reported assessment as well as the tablet count. Conclusion: This research suggests that appropriately designed written material can have a positive impact in improving adherence and, together with verbal consultation, are essential for enabling patients to make appropriate decisions about their medicine taking

E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection.

Integrase strand-transfer inhibitor (InSTI)-based regimens are the preferred combinations for naïve HIV-infected individuals. Polymorphic substitutions that reduce InSTIs activity have been described, with E157Q being one of the most frequently found. This study aimed to evaluate the prevalence of E157Q substitution in newly diagnosed acute/recent HIV cases and the presence of transmission clusters. Prospective cohort study in patients with acute/recent HIV infection. Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of less than 6 months from May 2015 to May 2017. Sequences were obtained by ultra-deep sequencing. Phylogenetic inferences were performed using maximum likelihood trees constructed with Mega 6.06. Bootstrap values of 75% or greater were defined for cluster assignment. Follow-up was, at least, 1 year. In six out of 67 consecutive patients (8.95%, 95% confidence interval 4.17-18.19) with acute/recent HIV infection, strains carrying the E157Q InSTI substitution were detected. All cases were MSM patients infected with subtype B strains. No other resistance substitutions were detected in these cases. Median viral load was 5.33 (interquartile range: 4.54-5.71) log10 copies/ml and, in all cases, the mutational viral load was high (>95%). Three cases were included in transmission clusters. Three cases responded to dolutegravir-based regimens; nonnucleoside reverse transcriptase inhibitor-based regimens were used for the other case(s). E157Q substitution, reducing raltegravir and elvitegravir activity, was frequently found in acute/recent HIV cases. All cases were infected with subtype B, and some were included in clusters. Cases treated with dolutegravir-based regimens had good virological response

Epidemiological changes of acute/recent human immunodeficiency virus type 1 infection in Barcelona, Spain (1997-2015): a prospective cohort study

To describe the epidemiology of acute/recent human immunodeficiency virus (HIV) infection over two decades in Barcelona (Spain)