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.

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.

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

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.

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.

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.

Risk factors for follow-up interruption of HIV patients in French Guiana.

French Guiana is the region of France where the HIV epidemic is most prevalent. To determine the risk factors for being lost for follow-up, we followed a cohort of 1,213 patients between 1992 and 2002 and determined which variables were related to two definitions of being lost to follow-up: permanently disappearing from HIV clinics and coming back after more than 1 year of missed appointments. The incidence rate for permanent follow-up interruption was 17.2 per 100 person-years. The median time to lost to follow-up was 4.3 years (interquartile range = 1.4-8.4 years). Cox modeling showed that the younger age groups, foreigners, patients with initial CD4 counts at the time of HIV diagnosis less than 500/mm3, and patients followed before the availability of highly active antiretroviral therapy (HAART) were significantly more likely to be permanently lost to follow-up, suggesting that some of the patients may have died. When looking at temporary loss to follow-up, younger age groups, untreated patients, patients consulting before the availability of HAART, and patients with CD4 counts more than 500/mm3 were more likely to not come back for a period of more than 1 year.

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.

Risk factors for late HIV diagnosis in French Guiana.

Risk factors for delayed HIV diagnosis in French Guiana were studied in 1952 patients between 1992 and 2003. At the time of diagnosis, 30% of patients had less than 200 CD4 lymphocytes/mm3; age, male sex, and foreign nationality were independently associated with a low CD4 cell count. The availability of highly active antiretroviral therapy was not associated with an earlier HIV diagnosis. Promoting HIV information and testing should be done in several languages to reach minorities.

Histoplasmosis and acquired immunodeficiency syndrome: a study of prognostic factors.

We aimed to identify prognostic factors for AIDS-associated disseminated histoplasmosis. In a multivariate analysis, we found that dyspnea, a platelet count of <100,000 platelets/mm3, and lactate dehydrogenase levels of >2 times the upper limit of the normal range were significantly independently associated with the death of the patient during the first 30 days of antifungal treatment.

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.

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.

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 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.

Increased incidence of disseminated histoplasmosis following highly active antiretroviral therapy initiation.

To determine whether the initiation of highly active antiretroviral therapy (HAART) had any influence on the incidence of disseminated histoplasmosis, a retrospective cohort study was performed on 1551 patients followed for up to 12 years. After controlling for CD4 counts, age, and sex, patients taking HAART for 2 months or less were more likely to develop disseminated histoplasmosis than untreated patients (respectively, hazard ratio, 3.7 [95% confidence interval, 1.57-8.7]; P = 0.003). In contrast, after 6 months of HAART, treated patients were less likely to develop disseminated histoplasmosis than untreated patients (hazard ratio, 0.6 [95% confidence interval, 0.37-0.98], P = 0.04). This increased incidence suggests that the initiation of HAART and the subsequent immune reconstitution may reveal undiagnosed latent disseminated histoplasmosis.