Clinical and laboratory features of COVID-19 illness and outcomes in immunocompromised individuals during the first pandemic wave in Sydney, Australia.

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March-October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n = 12), secondary immunosuppression (N = 8) and those with primary or acquired immunodeficiency (i.e. HIV; N = 7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.

Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D2EFT.

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.

Health status and healthcare trajectory of vulnerable asylum seekers hosted in a French Reception Center.

BACKGROUND: Europe lacks studies related to asylum-seekers' health. METHODS: We described the health status, healthcare and follow-up of men seeking asylum, accommodated in a primary reception center in Paris (CPA). This observational study included volunteer patients presenting for care at the CPA primary care unit (PCU) from January to March 2018. They could be referred to on-site GPs and psychiatrists or to surrounding healthcare facilities. After their asylum application, patients were transferred to other French accommodation centers. PCU healthcare professionals could make referrals for close medical reassessments after transfer. RESULTS: The 728 included men came mostly from Central Asia or Middle East (65%) and Africa (34%). Seventy percent reported violence during migration. Seventy-five percent (547/728) were referred to on-site GPs, 20% to psychiatrists. During patients' stay at CPA, 67% (144/214) of referrals to surrounding healthcare facilities led to performed consultations. Seven percent of all the included patients (49/728) were referred for frequent communicable infectious diseases screening. Final diagnoses (n = 1108) included 31% infectious diseases and 7% psychiatric disorders. When post-transfer accommodation centers could be reached, 69% (33/48) of the medical referrals had led to a scheduled appointment. CONCLUSIONS: The healthcare trajectory at CPA could benefit from optimization of infectious and psychiatric screenings, and improved coordination of care and follow-up.

National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review.

BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Can we talk about price with patients when choosing antiretroviral therapy? A survey with people living with HIV and prescribers in France.

OBJECTIVE: The aim of this study was to evaluate people living with HIV (PLWH) and HIV specialist prescribers' perception of discussing antiretroviral therapy (ART) price in PLWH's care and the acceptability of choosing or switching to various types of less expensive ARTs. DESIGN: Cross-sectional surveys (one in a convenience sample of PLWH and one in a voluntary response sample of HIV specialist prescribers). SETTING AND PARTICIPANTS: The surveys were conducted among PLHW attending an HIV clinic in the North of Paris (cohort of 4922 PLWH in 2016), and HIV specialists working in French HIV clinics (210 across 12 districts/28), between January and June 2016. METHOD: Self-administered questionnaires were constructed using data collected during focus groups with PLWH and prescribers. Pretests were carried out to select the questions and items. Descriptive analyses of the 129 complete questionnaires of PLWH and 79 of prescribers are presented. RESULTS: Among PLWH, 128/129 were on ART and 54% (69/128) gave a fair estimation of the price of their current regimen. Among prescribers, 24% (19/79) thought that their patients knew this price. Taking into account the price of ART was not perceived as a negative step in the history of French response to HIV epidemic for 53% (68/129) of PLWH and 82% (65/79) of prescribers. Seventy-seven PLWH (60%) would agree to switch to less expensive antiretroviral regimens (as effective and with similar adverse events) if pills were bigger; 42 (33%) if there were more daily doses, and 37 (29%) if there were more pills per dose; prescribers were more circumspect. CONCLUSION: A high proportion of PLWH gave a fair estimate of their ART price and this seemed unexpected by HIV specialists. Consideration of drug prices when choosing ART was perceived as conceivable by PLWH and prescribers if effectiveness and tolerance were also considered.

Incidence and risk factors for medical care interruption in people living with HIV in a French provincial city.

OBJECTIVES: The aim of our study was to identify HIV-positive patients at risk of medical care interruption (MCI) in a provincial city of a high-income country. METHODS: We estimated the incidence rate of MCI in 989 individuals followed in an HIV clinic in Caen University Hospital, Normandy, France, between January 2010 and May 2016. We enrolled patients over 18 years old who were seen at the clinic at least twice after HIV diagnosis. Patients were considered to be in MCI if they did not attend care in or outside the clinic for at least 18 months, regardless of whether or not they came back after interruption. We investigated sociodemographic, clinical and immunovirological characteristics at HIV diagnosis and during follow-up through a Cox model analysis. RESULTS: The incidence rate of MCI was estimated to be 3.0 per 100 persons-years (95% confidence interval [CI] = 2.6-3.5). The independent risk factors for MCI were a linkage to care >6 months after HIV diagnosis (hazard ratio [HR] = 1.14; 95% CI = 1.08-1.21), a hepatitis C coinfection (HR = 1.76; 95% CI = 1.07-2.88), being born in Sub-Saharan Africa (HR = 2.18; 95% CI = 1.42-3.34 vs. in France) and not having a mailing address reported in the file (HR = 1.73; 95% CI = 1.07-2.80). During follow-up, the risk of MCI decreased when the patient was older (HR = 0.28; 95% CI = 0.15-0.51 when >45 vs. ≤ 30 years old) and increased when the patient was not on antiretroviral therapy (HR = 2.78; 95% CI = 1.66-4.63). CONCLUSIONS: Our findings show that it is important to link HIV-positive individuals to care quickly after diagnosis and initiate antiretroviral therapy as soon as possible to retain them in care.

Treatment as prevention (TasP) and perceived sexual changes in behavior among HIV-positive persons: a French survey in infectious diseases departments in Paris.

We evaluated awareness of treatment as prevention (TasP) among adults people living with HIV (PLHIV) in five infectious disease departments in Paris, then how they perceived its impact on their sexual well-being. This cross-sectional multicenter survey was conducted in 2014 during scheduled clinical appointments using a self-administered questionnaire. We analyzed 520 questionnaires (42% women, 54% men of whom 57% were MSM [men who have sex with men]). 75% of women were born abroad, most commonly in sub-Saharan Africa, whereas 64% of men were French-born. The mean time since HIV diagnosis was 12.8 ± 7.8 years. Eighty-seven percent [84-90%]95% reported being aware of the impact of ART on HIV transmission, 94% MSM, 86% women, 83% heterosexual men. PLHIV reported that they gained awareness of TasP through medical doctors (86%). The fear of transmission was perceived as alleviated for 73% [69%;78%]95%, more often among MSM; the sexual life was reported to be improved for 28% [24%;33%]95%; and ART adherence to be improved for 45% [40%;50%]95%, more often among women. The awareness of TasP was relatively high, but it seems important to understand the features of male and female populations of PLHIV to adapt counseling during follow-up appointments, as women's answers differed in various regards.

Incidence of and risk factors for medical care interruption in people living with HIV in recent years.

OBJECTIVES: With HIV treatment as a prevention strategy, retention in care remains a key for sustained viral suppression. We sought to identify HIV-infected patients at risk for medical care interruption (MCI) in a high-income country. METHODS: The HIV-infected patients enrolled had to attend the clinic at least twice between January 2010 and October 2014 and were followed up until May 2016. MCI was defined as patients not seeking care in or outside the clinic for at least 18 months, regardless of whether they returned to care after the interruption. The association between MCI and sociodemographic, clinical, and immuno-virological characteristics at HIV diagnosis and during follow-up was assessed using Cox models. RESULTS: The incidence rate of MCI was 2.5 per 100 persons-years (95% confidence interval [CI] = 2.3-2.7). MCI was more likely in patients who accessed care >6 months after diagnosis (hazard ratio [HR] = 1.30, 95% CI = 1.10-1.54 vs. ≤6 months) or did not report a primary care physician (HR = 2.40; 95% CI = 2.03-2.84). MCI was less likely in patients born in sub-Saharan Africa (HR = 0.75, 95% CI = 0.62-0.91 vs. born in France). During follow-up, the risk of MCI increased when the last CD4 count was ≤350 (HR = 2.85, 95% CI = 2.02-4.04 vs. >500 cells/mm3) and when the patient was not on antiretroviral therapy (HR = 3.67, 95% CI = 2.90-4.66). CONCLUSIONS: The incidence of MCI is low in this hospital that serves a large proportion of migrants. Low or no recorded CD4 counts for a medical visit could alert of a higher risk of MCI, even more in patients who accessed HIV care late or did not report a primary care physician.

Metabolic syndrome and endocrine status in HIV-infected transwomen.

BACKGROUND: HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. METHODS: A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. RESULTS: A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. CONCLUSION: In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.

Budget impact of antiretroviral therapy in a French clinic cohort.

OBJECTIVES: In this study, we first assessed costs associated with the use of antiretroviral therapy (ART) in an infectious diseases University Hospital Clinic; second, we evaluated characteristics associated with these costs and finally simulated the impact on the overall ART budget of switching first-line and second-line regimens to less-costly regimens (as effective and well tolerated). DESIGN: Cohort analysis including persons living with HIV (PLHIV) aged at least 18 years on ART to estimate ART costs during 2014. METHODS: The current study was conducted in the Bichat-Claude Bernard University Hospital Clinic in Paris, France, where 4501 PLHIV consulted in 2014. We used the medical database Nadis to describe patients' ART, characteristics and estimated costs. When assessing the budgetary impact of potential switches, we considered patients' history of failure, CD4 cell count, plasma viral load, resistance mutations, hepatitis B surface antigen or HLAB5701 profile. RESULTS: A total of 4238 of 4501 patients were on ART (94%). The total annual cost of ART prescribed was estimated at &OV0556;48 280 200 in 2014; first/second (simplification)-line regimens represented 25% (1076/4238) of the treated PLHIV and 23% (&OV0556;11 209 000) of the annual cost. For these PLHIV, we considered switches from the most common ART regimens (protease inhibitor boosted by ritonavir or nonnucleoside reverse transcriptase inhibitor + two nucleoside reverse transcriptase inhibitors) to less-expensive regimens. We found savings ranging from &OV0556;36 100 to 1472 600/year. Savings were the highest when we considered switching to generic-based regimens or from protease inhibitor-based triple therapy to protease inhibitor monotherapy. CONCLUSION: Costs associated with ART prescriptions are very high. Switches to generic-based regimens are associated with large savings. However, those targeting protease inhibitor regimens are also associated with substantial savings and should be considered.

HIV-1 Pol Gene Polymorphism and Antiretroviral Resistance Mutations in Treatment-Naive Adult Patients in French Guiana Between 2006 and 2012.

Little information is available on the molecular epidemiologic profile of HIV-1 in French Guiana, the French department with the highest HIV/AIDS incidence. To follow the evolution of HIV-1 diversity, we carried out a molecular analysis of HIV-1 isolates from 305 treatment-naive patients between 2006 and 2012. Protease and reverse-transcriptase sequences were obtained for subtype characterization, polymorphism analysis, and identification of drug resistance mutations. Of 305 HIV-1 strains, 95.1% were subtype B viruses. The overall prevalence of transmitted drug-resistance mutations (TDRMs) was 4.6% (14/305), ranging from 1.9% to 7.1% depending on the year. This study shows a low level of HIV-1 genetic diversity and a moderate prevalence of TDRMs with no evidence of an increasing trend over the study period. Nevertheless, the strong genetic polymorphism observed on both genes may be of concern for long-term treatment of people living with HIV-1 and thus deserves continuous monitoring.

Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case-series experience.

Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA-ZDV-DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV-1 RNA load (pVL) >50 c/ml (>100 for HIV-2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV-1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA-ZDV-DTG containing-regimen with 48 weeks (W48) of follow-up. Out of 5 patients, 2 were infected with HIV-2. At PFA-ZDV-DTG initiation, CD4 cell count was (/mm(3) ) of 64, 40, 10, in HIV-1, and 37, 199, in HIV-2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV-1, and 3.6, 4.2, in HIV-2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1-2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV-1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV-2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV-infected patients, failing cART and without other therapeutic options, a PFA-ZDV-DTG combination therapy could be effective. Renal adverse events should be monitored.

Risk factors for delayed access to specialized care in French Guiana.

The variables influencing the interval between diagnosis and effective access to specialized care were studied in a cohort of 2,661 human immunodeficiency virus (HIV)-positive patients in French Guiana between 1992 and 2008. Patients with a subsequent follow-up interruption were significantly more likely to have a delayed first consultation after the HIV diagnosis. Ordinal logistic regression showed that younger persons, women, and French citizens were independently associated with greater delays between the HIV diagnosis and the first specialized consultation. However, persons with acquired immunodeficiency syndrome (AIDS) were less likely to have a delay between the HIV diagnosis and the first specialized consultation. Focusing on the link between the private sector and specialized health care may shorten delays and improve care and follow-up.

What is AIDS in the Amazon and the Guianas? Establishing the burden of disseminated histoplasmosis.

The pathogen ecology of Amazonian regions may lead to specific differences in the most frequent clinical presentations of acquired immunodeficiency syndrome (AIDS). A retrospective cohort study was thus conducted to describe the main AIDS-defining events in French Guiana. Disseminated histoplasmosis was the most frequent opportunistic infection (15.4/1000 person years).