Background. The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary... Show moreBackground. The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders.Methods. The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.Results. Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60-66), 86% were male, and median CD4(+) T-cell count was 650/mu L (IQR, 423-941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24-46) to 4317 BAU/mL (95% CI, 3275-5360) (P<.0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4(+) T cells (P=.04) and S-specific B cells (P=.02) was observed.Conclusions. An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Show less
Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently... Show moreBackground: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/mu L (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.5080.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as > 300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ Tcell count 250-500 cells/mu L (2.845, 95% CI 1.876-4.314, p < 0.001) or > 500 cells/mu L (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-gamma, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ Tcell counts of recipients.Conclusions: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Author summary: Why was this study done? The efficacy of SARS-CoV-2 vaccines in people living with HIV (PLWH) is not well characterised.HIV has been repeatedly associated with lower immune responses to other vaccines, and this diminished response is strongly correlated with CD4+ T-cell count.The SARS-CoV-2 vaccines BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S showed good protection against severe COVID-19 and hospitalisation in phase III registration trials; however, the number of PLWH in these trials was very limited. What did the researchers do and find?We initiated a nationwide prospective study including 1,154 PLWH and 440 HIV-negative controls.We show that lower antibody levels are seen in PLWH compared to controls after completion of the vaccination schedule, regardless of the vaccine received.All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In multivariable analyses, having HIV had the largest negative effect on antibody responses following vaccination, more than both age and sex. Following mRNA vaccination, the antibody response was higher in PLWH with CD4+ T-cell counts between 250 and 500 cells/mu L or higher than 500 cells/mu L (both p < 0.001), while those with <250 cells/mu L had a lower response. In PLWH, age above 65 years and being born as male were associated with lower antibody concentrations as well (both p < 0.001). What do these findings mean? Clinicians should particularly be aware of potential lower vaccine responses in elderly PLWH and those with lower cellular immunity or evidence of acquired immunodeficiency syndrome.PLWH may require additional vaccinations on top of standard regimens to achieve and keep protection against SARS-CoV-2 at similar levels to HIV-negative controls.In these participants, with the vaccines studied, mRNA-based vaccine strategies are to be preferred over vector-based ones. Show less
Background In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide... Show moreBackground In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015.Methods In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years.Findings Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5.2 per 1000 person-years [95% CI 5.0-5.5]). The highest incidence was observed in men who have sex with men (MSM; 7.7 per 1000 person-years [7.3-8.2]) and was lower in people who inject drugs (PWID; 1.7 per 1000 person-years [0.7-4.1]) and other key populations (1.0 per 1000 person-years [0.8-1.2]). In MSM, incidence increased in 2007 to 14.3 per 1000 person-years and fluctuated between 8.7 and 13.0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6.1 cases per 1000 person-years and remained steady between 4.1 and 4.9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26.9 per 1000 person-years [95% CI 23.9-30.3]). The highest incidence rate was observed in MSM (38.5 per 1000 person-years [33.9-43.7]) and was lower in PWID (10.9 per 1000 person-years [3.5-33.8]) and other key populations (8.9 per 1000 person-years [6.3-12.5]). In MSM, reinfection incidence fluctuated between 38.0 and 88.9 per 1000 person-years from 2006 to 2015, reaching 55.6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41.4 per 1000 person-years, followed by further decreases to 24.4 per 1000 person-years in 2017 and 11.4 per 1000 person-years in 2019.Interpretation The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
Bree, G.J. de; Sighem, A. van; Zuilhof, W.; Bergen, J.E.A.M. van; Prins, M.; Heidenrijk, M.; ... ; HIV Transmission Elimination 2019
Purpose of review Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design... Show morePurpose of review Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design effective approaches to eliminate transmission of these pathogens. The HIV Transmission Elimination AMsterdam (H-TEAM) Initiative, a consortium of relevant stakeholders involved in HIV prevention and care, designed an integrated approach to curb the HIV epidemic in Amsterdam, including providing preexposure prophylaxis (PrEP), increasing awareness of acute HIV infection, offering same-day test and treat, and improving indicator disease-driven HIV testing. Recent findings In 2013, approximately 230 people in Amsterdam were newly diagnosed with HIV, largely belonging to one of two key affected populations, namely MSM and people with a migration background. Since the start of H-TEAM in 2014, a decrease in new diagnoses was observed (130 in 2017), with an increasing proportion of MSM who had been diagnosed with a recent infection. The H-TEAM shows that a city-based concerted effort is feasible. However, major challenges remain, such as reducing the number of late HIV diagnoses, and identifying and providing appropriate services to a diminishing group of individuals who are likely the source of transmission. Show less
Zoest, R.A. van; Law, M.; Sabin, C.A.; Vaartjes, I.; Valk, M. van der; Arends, J.E.; ... ; Elst-Laurijssen, D.H. 2019
Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how... Show morePolicy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers. Show less
Objective:Successful treatment of people infected with HIV requires that patients are retained in HIV care, use combination antiretroviral therapy (cART) and ultimately reach and sustain viral... Show moreObjective:Successful treatment of people infected with HIV requires that patients are retained in HIV care, use combination antiretroviral therapy (cART) and ultimately reach and sustain viral suppression. Our aim was to identify health facility characteristics associated with these steps in the cascade of HIV care.Design:Retrospective cohort study.Methods:We included data from all adult HIV-1-infected patients who entered care in the Netherlands between 2007 and 2013 (N=7120). Multivariate logistic regression was used to examine the associations between health facility characteristics and the outcomes currently in care', initiated cART', and viral suppression'.Results:The proportion of patients currently in care' was high in all 26 treatment centres. cART initiation was positively associated with the accreditation of the health facility [OR (odds ratio): 1.62; 95% CI (confidence interval): 1.18-2.23] and the performance of an internal audit in the preceding 3 years (OR: 1.36; 95% CI: 1.02-1.81). The odds of cART initiation were higher in middle-sized (OR: 2.00; 95% CI: 1.25-3.21) and large HIV treatment centres (OR: 1.80; 95% CI: 1.14-2.84) compared with small centres (<300 HIV-infected patients). Viral suppression was negatively associated with the presence of a social worker in the HIV treatment team (OR: 0.62; 95% CI: 0.43-0.91).Conclusions:Our results confirm that appointing expert HIV treatment centres facilitates retention in care and that a minimum volume requirement may be desirable. Our findings suggest that quality assessment through accreditation and the measurement of performance benefits the delivery of HIV care. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. Show less
We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a... Show moreWe longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load (<15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART was initiated, plasma viral load was similar. After TI, the numbers of CD8(+) T cells increased more in individuals without viral control, whereas individuals maintaining a low viral load showed a more pronounced increase in HIV-specific CD8(+) T-cell numbers. No differences were seen in the number or percentage of cytokine-producing HIV-1-specific CD4(+) T cells, or in proliferative capacity of T cells. Four weeks after TI, the magnitude of the total HIV-1-specific CD8(+) T-cell response (IFN-gamma(+) and/or IL-2(+) and/or CD107a(+)) was significantly higher in individuals maintaining viral control. Degranulation contributed more to the overall CD8(+) T-cell response than cytokine production. Whether increased T-cell functionality is a cause or consequence of low viral load remains to be elucidated. Show less
Sighem, A. van; Gras, L.; Reiss, P.; Brinkman, K.; Wolf, F. de; ATHENA Natl Observational Cohort S 2010
Objective: To compare life expectancies between recently diagnosed HIV-infected patients and age and sex-matched uninfected individuals from the general population. Design: National observational... Show moreObjective: To compare life expectancies between recently diagnosed HIV-infected patients and age and sex-matched uninfected individuals from the general population. Design: National observational HIV cohort in the Netherlands. Methods: Four thousand, six hundred and twelve patients diagnosed with HIV between 1998 and 2007 and still antiretroviral therapy-naive as of 24 weeks after diagnosis were selected. Progression to death compared to the age and sex-matched general population was studied with a multivariate hazards model in 4174 (90.5%) patients without AIDS events at 24 weeks. Life expectancy and number of life years lost were calculated using the predicted survival distribution. Results: During 17 580 person-years of follow-up since 24 weeks after diagnosis [median follow-up 3.3 years, interquartile range (IQR) 1.6-5.8], 118 deaths occurred, yielding a mortality rate of 6.7 [95% confidence interval (CI) 5.5-8.0] per 1000 person-years. Median CD4 cell counts at 24 weeks were 480 cells/mu l (IQR 360-650). According to the model, the median number of years lived from age 25 was 52.7 (IQR 44.2-59.3; general population 53.1) for men and 57.8 (49.2-63.7; 58.1) for women without CDC-B event. The number of life years lost varied between 0.4 if diagnosed with HIV at age 25 and 1.4 if diagnosed at age 55; for patients with a CDC-B event this range was 1.8-8.0 years. Conclusion: The life expectancy of asymptomatic HIV-infected patients who are still treatment-naive and have not experienced a CDC-B or C event at 24 weeks after diagnosis approaches that of non-infected individuals. However, follow-up time is short compared to the expected number of years lived. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins Show less
