Forty Years of HIV Research in French Guiana: Comprehend to Combat.

The drivers of the HIV epidemic, the viruses, the opportunistic infections, the attitudes and the resources allocated to the fight against HIV/AIDS, vary substantially across countries. French Guiana, at the crossroads between Amazonian South America and the Caribbean, constitutes a singular context with poor populations and rich country health funding, which has allowed researchers to gather lots of information on the particulars of our epidemic. We aimed to focus on the little known story of forty years of HIV research in French Guiana and emphasize how local research intertwined with public health action has yielded continuous progress, despite the difficult social conditions of the affected population. We searched Web of Science and associated local experts who worked through much of the epidemic in selecting the most meaningful products of local research for clinical and public health outcomes in French Guiana. Research tools and facilities included, from 1991 onwards, the HIV hospital cohort and the HIV-histoplasmosis cohort. Ad hoc studies funded by the ANRS or the European Regional Development fund shed light on vulnerable groups. The cumulative impact of prospective routine collection and focused efforts has yielded a breadth of knowledge, allowing for informed decisions and the adaptation of prevention, testing and care in French Guiana. After this overview, we emphasize that the close integration of research and public health was crucial in adapting interventions to the singular context of French Guiana.

Chapitre 8. Annoncer ou pas la découverte d'anomalies non sollicitées lors d'un test génétique à séquençage haut débit ?

OBJECTIVE: New genome sequencing techniques allow new approaches in medical genetics, in particular by facilitating the diagnosis of genetic diseases. However, their use also leads to unsolicited genetic findings being uncovered. This type of discovery raises ethical, legal and psychological considerations. The objective of this psychological research was to study the different positions of patients, health professionals and general public regarding the acceptability of the announcement of unsolicited findings revealed during a high-throughput sequencing genetic test. METHOD: the first exploratory study aimed, through non-directive research interviews conducted with 13 patients of a medical genetics service, to understand the psychological repercussions linked to the announcement of a result of a targeted genetic test and to know the patients’ desires regarding the announcement of unsolicited findings if the test had been a high-throughput genetic test. The second study, using a quantitative methodology, aimed to identify the judgment policies of 144 patients, 94 healthcare professionals and 211 people from the general public concerning the acceptability of this type of disclosure. RESULTS: The cluster analyses highlighted six judgment policies as to whether or not to disclose the discovery of unsolicited anomalies: “Tell everything”, “Tell even in part”, “Tell everything unless desperate”, “Undecided”, “Do not tell” and “Do not tell if no prevention”. The participants positioned themselves differently, in particular according to the patient’s consent. CONCLUSION: This research shows the variability of positioning and the importance of consent in the acceptability of the disclosure of unsolicited findings. However, one of the limitations of the study lies in the fact that in medical clinic, acceptability and acceptance may vary over time. A longitudinal study would undoubtedly afford a better understanding of the psychological progress of patients in this type of care pathway..

Attitudes of French populations towards the disclosure of unsolicited findings in medical genetics.

Next-generation sequencing techniques enable unsolicited findings to be detected. This discovery raises ethical questions concerning the return of these findings. Our study aimed to highlight the views of the general public, patients under supervision and health professionals concerning the acceptability of disclosing unsolicited results to patients. In total, 449 participants assessed scenarios, consisted of all combinations of three factors (patient's information and consent, prevention and treatment of the unsolicited disease and doctor's decision). The response profiles were grouped into six clusters. The participants took ethical aspects into account, but health professionals also considered the medical aspects to a greater extent.

High prevalence of human papillomavirus infection in HIV-infected women living in French Antilles and French Guiana.

An association between HIV infection and cervical cancer, a major public health issue worldwide, has been reported. The aim of this study was to estimate the prevalence of human papillomavirus (HPV) infection and the distribution of HPV genotypes in HIV-infected women living in French Antilles and Guiana and to determine HIV-related characteristics associated with HPV infection. This cross-sectional study included 439 HIV-infected women who were followed between January 2011 and May 2014. Variables related to HIV infections were collected, and cervical samples were analysed to determine HPV genotypes. The median age of the population was 46 years. Estimated prevalence of HPV and high-risk (HR)-HPV infection were 50.1% IC95 [45.4-54.7] and 42% IC95 [37.3-46.6], respectively. HR-HPV 16, 52, 53 or intermediate risk-HPV-68 were found in 25% to 30% of the HPV-infected patients. Gynaecological screening revealed abnormal cervical smear in 24% and 42% of HR-HPV-negative and HPV-positive women, respectively (p = 0.003). Approximately 90% of women were on antiretroviral therapy (ART). Demographic characteristics associated with a higher prevalence of HPV infection included alcohol consumption. Regarding HIV-related characteristics, current therapy on ART, its duration, and undetectable plasma concentrations of RNA-HIV1 were associated with a lower risk of HPV infection. Infection rate with HR-HPV was higher than what is commonly reported in HIV-negative women worldwide and was more likely in women with incomplete HIV suppression. These results highlight the need for supporting adherence to ART, cervical cytology, HPV testing and HPV vaccination.

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.

Judging health risk as a function of risk factors and type of illness: Do people weight risk factors in a flexible way?

We examined the extent to which lay people and health professionals are able to assess occurrence risks for multifactorial diseases. We asked 341 participants to assess the risk of developing lung cancer, coronary artery disease or rheumatoid arthritis in 16 scenarios, each featuring a combination of four factors (family history, daily alcohol intake, daily tobacco consumption and genetic test results). Participants considered all factors. However, they accorded more weight to tobacco and genetic test results. Moreover, it appears that where one of the factors (e.g. the presence of the incriminated gene) exerted a strong influence, the influence of the other factor(s) was correspondingly weaker. The health risk judgements of health professionals were more dependent on the specific disease and were also influenced to a greater degree by genetic information than lay people.

Patients' motives for consenting or refusing to participate in a clinical trial in organ transplantation.

BACKGROUND: The goal of this health-psychology study was to investigate the range of motives that make someone consent or refuse participation in a clinical transplant trial. METHODS: The study involved (i) preparatory interviews with five transplant patients who took part in clinical trials and five persons from the general public; (ii) we created a questionnaire with scaled responses; (iii) we selected 468 patients, divided into two groups: patients waiting for a transplant and patients who already had a transplant; (iv) we obtained patient consents, sent out the questionnaire, and recorded responses; (v) data were analysed using descriptive statistics, exploratory factorial analyses, correlations and regressions. RESULTS: Two hundred and ten patients answered the questionnaire. Motives were classified into the following: (i) Motives to consent participating in a clinical trial (pride in participating, hope for better quality of life, sufficient and clear information, discussion with others participating in a trial, altruism); or (ii) Motives to refuse participating (no information on medical teams, lack of explanation, fear of additional expenses, being considered a "guinea pig"). CONCLUSIONS: This study contributes to our understanding of the motivations of patients who accepted or refused participation in a clinical transplantation trial.

Antiretroviral therapy promotes an inflammatory-like pattern of human T-cell lymphotropic virus type 1 (HTLV-1) replication in human immunodeficiency virus type 1/HTLV-1 co-infected individuals.

Upon antiretroviral therapy (ART) human immunodeficiency virus (HIV)/human T-cell lymphotropic virus type 1 (HTLV-1) co-infected individuals frequently develop neurological disorders through hitherto unknown mechanisms. Here, we show that effective anti-HIV ART increases HTLV-1 proviral load through a polyclonal integration pattern of HTLV-1 in both CD4(+) and CD8(+) T-cell subsets that is reminiscent of that typically associated with HTLV-1-related inflammatory conditions. These data indicate that preventing ART-triggered clonal expansion of HTLV-1-infected cells in co-infected individuals deserves investigation.

French lay people's views regarding the acceptability of involuntary hospitalization of patients suffering from psychiatric illness.

PURPOSE: To understand how lay people and health professionals in France judge the acceptability of hospitalizing a psychiatric patient against his will. METHODS: 123 lay people, 20 nurses, 5 psychologists, and 6 physicians judged the acceptability of involuntary hospitalization in each of 36 scenarios consisting of all combination of 4 factors: patient's adherence to treatment (agrees to take his medications or not); risk of suicide (none, immediate, multiple past attempts); risk of harming others (none, immediate, history of violence against others); attitude of patient's family (favorable to involuntary hospitalization or not). The judgment data were subjected to cluster analysis and subsequently to analysis of variance. RESULTS: 4 clusters were identified and labeled according to the factors that affected judgments: Never Favorable (7 participants, with mean acceptability judgment of 1.30 on a scale of 0-10); Threat to Others (35, with mean judgment of 8.68 when risk high, 2.94 when risk low), Threat to Others or Self and Adherence (88, with mean judgment of 6.89), and Always Favorable (24, with mean judgment of 8.41). CONCLUSIONS: 95% of participants agreed that involuntary hospitalization is acceptable under certain conditions, especially - in accordance with French law - when the patient presents a risk to others.

Donating organs: a theory-driven inventory of motives.

Two studies examined the motives that lay behind patients' acceptance or reluctance at donating organs after death. They also examined the way these motives were related to demographic characteristics, personality, and signing a donor card. Six separable motives for donation were found: Financial Incentive, Humanistic or Religious Duty, Positive Consideration from Others, Living on Through a Receiver, Gift of Life, and Close Others. Five motives for not donating were found: Preserving the Absolute Integrity of the Corpus, Strict Individualism, Lack of Control over the Use of the Organs, Anonymity of the Procedure, and Respecting Family Wishes. These motives were linked to personality factors in a meaningful way. Willingness to sign was higher among female participants and among participants with lower scores on Integrity of the Corpus and higher scores on Duty and Gift of Life. When Integrity of the Corpus scored highly, however, the effect of the other factors was practically eliminated. In other words, Integrity of the Corpus acted as a protected value: Trying to change people's belief that the integrity of the corpus at death is a sacrosanct issue would come with its own ethical issues.

Breaking patient confidentiality: comparing Chilean and French viewpoints regarding the conditions of its acceptability / Ruptura de la confidencialidad: una comparación entre las perspectivas chilena y francesa respecto a las condiciones de su aceptabilidad

Para examinar las condiciones bajo las cuales una muestra de participantes del público general y de profesionales de la salud chilenos considera aceptable que un médico rompa la confidencialidad para proteger al cónyuge de un paciente que padece una enfermedad de transmisión sexual (ETS), doscientos siete participantes (personas del público general y profesionales de la salud), evaluaron la aceptabilidad de dicha ruptura en 48 escenarios, que consistieron en todas las posibles combinaciones de 5 factores (gravedad de la enfermedad, tiempo que se toma conversar sobre la enfermedad con el paciente, intento del paciente por informar a su cónyuge sobre su enfermedad, intento del paciente por adoptar una conducta de protección hacia su cónyuge, y decisión del médico de consultar a un especialista en ETS). Un análisis de racimos reveló grupos de participantes que encontraron la ruptura de la confidencialidad oscilando entre “siempre aceptable” y “nunca aceptable”. A pesar de las diferencias de legislación y códigos de ética, las muestras de público general no difirieron mucho en sus convicciones personales respecto a las circunstancias de protección o ruptura de la confidencialidad del paciente. En contraste, los médicos chilenos apoyaron menos que los franceses mantener un completo respeto a la confidencialidad del paciente en todos los casos...

To examine the conditions under which lay people and health professionals living in Chile and France find it acceptable for a physician to break confidentiality to protect the spouse of a patient with a sexually transmitted disease (STD), 207 lay persons and healthcare professionals indicated the acceptability of breaking confidentiality in 48 scenarios combining five factors: disease severity, time taken to discuss this with the patient, patient’s intent to inform his spouse about the disease, patient’s intent to adopt protective behaviors, and physician’s decision to consult an STD expert. A cluster analysis revealed groups that found breaking confidentiality “always acceptable”, requiring “consultation with an expert”, “depending on the many circumstances”, and “never acceptable” (11%)”. Despite differences in legislation and ethics codes, Chilean and French lay people showed similar personal convictions regarding the circumstances in which breaking patient confidentiality is acceptable. In contrast, Chilean physicians were much less supportive than French physicians of complete respect of patientconfidentiality in all cases...

Predictive factors and incidence of anxiety and depression in a cohort of HIV-positive patients in French Guiana.

A retrospective cohort study was conducted to determine the predictive factors and the incidence of anxiety and depression in a cohort of patients followed in French Guiana. A total of 2315 patients were followed for a total of 9116 years of follow-up. The incidence rate of first observed depression was 1.89 per 100 person years. The incidence rate of first observed generalized anxiety was 1.27 per 100 person years. A single failure Cox proportional hazards model showed that patients diagnosed <1 year (Hazard ratio (HR)=4.15; 95% CI=1.15-14.9; P=0.029), patients treated

Crack cocaine use increases the incidence of AIDS-defining events in French Guiana.

We conducted a retrospective cohort study to determine the influence of crack cocaine use on the outcomes of HIV infection. The use of crack cocaine was associated with an increased incidence of AIDS: 27.8 per 100 person-years versus 6.6 per 100 person-years for nonusers, adjusted hazard ratio = 3.8 (1.9-7.5), P < 0.001. More specifically, crack users had a greater incidence of disseminated histoplasmosis, pneumocystosis, pulmonary tuberculosis, bacterial pneumonia, oesophageal candidiasis, cerebral toxoplasmosis, salmonellosis, and genital herpes. The care of HIV-infected crack users is particularly challenging and requires additional efforts to reduce the high morbidity of these patients.

Increased incidence of leprosy following HAART initiation: a manifestation of the immune reconstitution disease.

A retrospective cohort study was conducted to determine whether the incidence of leprosy varied with the duration of antiretroviral therapy (ART). Between 1992 and 2006, seven cases of leprosy were observed. The incidence of leprosy in untreated patients was 0.7 per 1000 person-years, 13 per 1000 person-years in persons receiving HAART for more than 3 months and 0.9 per 1000 person-years for persons receiving HAART for more than 3 months. The adjusted hazard ratio was 18.5 (95% confidence interval, 1.6-217) with P = 0.02. In tropical areas where HAART is increasingly available, physicians should be aware of the possibility of incident leprosy shortly after HAART initiation.

A large French prospective cohort of HIV-infected patients: the Nadis Cohort.

OBJECTIVES: The aim of this article is to describe the development of a dynamic French cohort of HIV-infected patients, the methodological issues and decisions made, and the characteristics of the patients currently enrolled. METHODS: Data are collected during medical encounters. Data quality is ensured by automated checks during data capture, by regular controls, by annual assessments, and by ad hoc processes before any scientific analysis is performed. RESULTS: In September 2007, 10,458 patients representing 59,383 patient-years of follow-up were followed in our centres, including 446 with a first HIV diagnosis in the past year. Among these recently diagnosed patients, 25.6% presented with late diagnosis. Our cohort included 3017 women (28.8%). The women were less likely to be receiving highly active antiretroviral therapy (HAART) than men, and when treated were less likely to be receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Our network includes medical centres in overseas territories (1105 patients living overseas). In this particular population, women represented 38.5% of the patients, and the probable route of infection was heterosexual in 75.7% of the patients. Despite epidemiological and social disparities, more patients had nondetectable viral loads when receiving HAART in overseas departments than in metropolitan France. CONCLUSION: The Nadis Cohort represents a collaboration of major French HIV treatment centres. In September 2007, the cohort database contained up-to-date information on more than 10,000 patients, of whom a significant proportion were women. As a consequence of the choices made when building the cohort and the efforts made to ensure the quality of the database, scientific studies are regularly performed using this cohort.

Is it acceptable for a psychiatrist to break confidentiality to prevent spousal violence?

STUDY QUESTION: When is it acceptable for a psychiatrist to break confidentiality to protect the wife of a potentially violent patient? METHODS: 153 lay persons, 13 nursing personnel, 10 physicians, and 10 psychologists in France indicated this acceptability in 48 scenarios. The scenarios were all combinations of 5 factors: gravity of threat (death or beating), certainty of mental illness (certain or not), time spent talking with patient (considerable or little), his attitude toward psychotherapy (rejection, indecision, or acceptance), and whether the physician consulted an expert. RESULTS: Lay people favored breaking confidentiality more than did nursing personnel or psychologists. Consulting an expert had greatest impact. Lay participants were composed of groups that found breaking confidentiality "always acceptable" (22 participants), "depending on many circumstances" (106), requiring "consultation with an expert" (31), and "never acceptable" (27). CONCLUSION: Lay people in France are influenced by situational factors when deciding if a psychiatrist should break confidentiality to protect a patient's wife.

AIDS-related Histoplasma capsulatum var. capsulatum infection: 25 years experience of French Guiana.

OBJECTIVE: Histoplasma capsulatum var. capsulatum infection is a major AIDS-defining illness in French Guiana. Although it affects South and Central American countries, the number of published cases is low. We present the largest series of AIDS-related histoplasmosis. The aim of this work is to describe clinical features and to help optimize investigations in settings where antigen detection methods are not available. DESIGN: Two hundred cases of AIDS-related histoplasmosis, diagnosed in the hospitals of French Guiana, were included retrospectively between 1982 and 2007. RESULTS: At the time of diagnosis, 92% of patients did not receive highly active antiretroviral therapy. CD4 cell count was less than 100 cells/microl for 80% of them. Most patients had fever, lymphadenopathies, and pulmonary and digestive symptoms. Neurological signs and skin/mucosal locations were less common. Other opportunistic infections were associated in 36.6% of cases (mostly tuberculosis). In most of the patients, lactic dehydrogenase was at least four times the normal value, and there was a moderate increase of aspartate aminotransaminase but not alanine aminotransaminase levels. Bone marrow aspirations were useful, but cultures of liver and lymphadenopathy specimens were the most contributive. Following treatment initiation, 17.5% died within a month. Presumptive treatment was started before diagnostic confirmation in 14.3% of the cases. CONCLUSION: In high prevalence settings, histoplasmosis often revealed AIDS in severely immunodeficient and poorly followed patients. In the absence of a quick sensitive technique, skin smear and fungal tissue cultures are contributive. Nevertheless, given the diagnostic delays and the poor prognosis, presumptive treatment with amphotericin B-containing regimens should be recommended when clinical and epidemiological contexts are evocative.

Increased incidence of cutaneous mycoses after HAART initiation: a benign form of immune reconstitution disease?

Immune reconstitution disease (IRD) has been associated with many pathogens after the initiation of antiretroviral therapy for advanced HIV infection. A retrospective cohort study was conducted to determine whether cutaneous mycoses were also associated with IRD. After adjusting for various confounding factors, the recent initiation of HAART was found to be associated with an increased incidence of cutaneous mycoses when compared with untreated patients.

Increased incidence of mucosal candidiasis after HAART initiation: a benign form of immune reconstitution disease?

Immune reconstitution after HAART initiation is often complicated by adverse clinical manifestations caused either by the unmasking of preexisting untreated opportunistic infections or the clinical deterioration of a known and treated opportunistic infection. The present study was conducted to determine whether the initiation of HAART was followed by an increase in the incidence of mucosal candidiases, a possible manifestation of immune reconstitution disease of the unmasking type.