Once-daily dolutegravir versus darunavir plus cobicistat in adults at the time of primary HIV-1 infection: the OPTIPRIM2-ANRS 169 randomized, open-label, Phase 3 trial.

BACKGROUND: Whether integrase strand transfer inhibitors (INSTIs) can decrease HIV-1 DNA levels more rapidly than boosted PIs during primary HIV-1 infection (PHI) is unknown. We hypothesized that once-daily dolutegravir/tenofovir/emtricitabine could reduce the viral reservoir through rapid viral replication control further than once-daily darunavir/cobicistat/tenofovir/emtricitabine. METHODS: The OPTIPRIM2-ANRS 169 study was a randomized (1:1), open-label, multicentre trial in adults with ≤5 or ≤3 HIV antibodies detected, respectively, by western blot or immunoblot in the last 10 days. The primary endpoint was total HIV-1 DNA levels in PBMCs at Week 48 (W48) adjusted for baseline levels. The main secondary endpoint was HIV-1 RNA level decrease. RESULTS: Between April 2017 and August 2018, 101 patients were included from 31 hospitals. Most patients were men (93%), the median age was 36 years and 17% were Fiebig stage ≤3. The median (IQR) plasma HIV-1 RNA and DNA levels were, respectively, 5.8 (5.0-6.6) and 3.87 (3.52-4.15) log10 copies/million PBMCs. The median (IQR) decreases in HIV-1 DNA levels at W48 were -1.48 (-1.74 to -1.06) and -1.39 (-1.55 to -0.98) log10 copies/million PBMCs in the dolutegravir and darunavir/cobicistat groups, respectively (P = 0.52). Plasma HIV-1 RNA levels were <50 copies/mL in 24% versus 0% of patients in the dolutegravir and darunavir/cobicistat groups at W4, 55% versus 2% at W8, 67% versus 17% at W12, and 94% versus 90% at W48, respectively. CONCLUSIONS: Dolutegravir-based and darunavir-based regimens initiated during PHI strongly and similarly decreased the blood reservoir size. Considering the rapid viral suppression during a period of high HIV-1 transmission risk, dolutegravir-based regimens are a major first-line option.

Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015-2016.

Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015-2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.

Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study.

BACKGROUND: Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016. METHODS: We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS. RESULTS: Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease. CONCLUSIONS: ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases.

Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016.

We report two cases of encephalopathy (one with seizures, one with electroencephalogram changes) in patients with Zika virus infection. The cases occurred on Martinique in February 2016, during the Zika virus outbreak. Awareness of the various neurological complications of Zika virus infection is needed for patients living in areas affected by Zika virus infections or for travellers to these areas.

Incidences and risk factors of first-line HAART discontinuation: a limitation to the success of the "seek, test, treat, and retain" strategy?

To evaluate the incidence and risk factors of first-highly active antiretroviral therapy (HAART) modifications/interruptions and their causes in a cohort of newly-treated patients by using a competing risk model. In nine centers of the French cohort Dat'AIDS, in 1 year and 2 years of censorship, a competing risk analysis was implemented in HIV1 patients aged 18 years or older first-treated between September 2002 and March 2012. In 4669 patients, 3628 modifications (77.7%) were observed (median: 13.5 months). Cumulative incidence in 1 year: 46.8% [45.4-48.3]; in 2 years: 65.3% [63.8-66.8]. Intolerance (n = 1167; 32.3%): in 1 year, except first-treated from 2002 to 2005, modifications were not different: 2002-2003 (24.6%) 2004-2005 (26.1%), 2006-2007 (19.4%), 2008-2009 (18.8%) and 2010-2011 (15.7%). Women, AIDS patients, and those aged 50 years and older had an excess risk. Therapeutic simplification (n = 1037; 28.6%): in 1 year, except first-treated from 2002 to 2003, modifications were not different: 2002-2003 (9.0%), 2004-2005 (16.0%), 2006-2007 (11.0%), 2008-2009 (15.7%) and 2010-2011 (10.0%). Conversely to injecting-drug-users and AIDS patients, women and first-treated with non-nucleosides had an excess risk. Therapeutic failure (n = 189; 5.2%): contrary to first-treated between 2002 and 2003 or 2008 and 2009, in 1 year as in 2 years, modifications were not different. In 1 year, 1.9% for 2004-2005, 1.6% for 2006-2007 and 1.2% for 2010-2011. Maximum viral load ≥5.0 log10 copies/ml and CD4 <200 cells/mm(3) had a high probability. The study of first-HAART modifications suggests that in 1-year follow-up, intolerance incidence in the recent calendar year is still as frequent as the previous period which may constitute a limitation to the success of the seek, test, treat, and retain.

Case Report: Pulmonary Leptospirosis Misdiagnosed as COVID-19.

We report the case of an 83-year-old woman with acute, febrile respiratory failure resulting from interstitial pneumonia that required high-flow oxygen therapy. This clinical picture, associated with the ongoing epidemiological situation, initially guided us toward a diagnosis of COVID-19. Based on SARS-CoV-2 reverse transcription-polymerase chain reaction negativity and the absence of anti-SARS-CoV-2 antibodies, a search for a differential diagnosis was conducted that led us to conclude a diagnosis of severe pulmonary leptospirosis This case highlights the need to engage in early discussions about differential diagnoses, including neglected tropical and subtropical diseases, during the COVID-19 era.

COVID-19 and Pasteurella multocida Pulmonary Coinfection: A Case Series.

OBJECTIVES: In COVID-19 patients, bacterial and fungal pulmonary coinfections, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, or Aspergillus, have been reported, but to our knowledge, no case has been reported due to Pasteurella multocida. PATIENTS AND METHODS: We describe three cases of Pasteurella multocida coinfections occurring during the 4th wave of COVID-19 in Martinique (French West Indies). RESULTS: All three cases were fatal; thus, Pasteurella multocida has to be considered as a potentially severe coinfection agent. CONCLUSIONS: Alteration of the epithelial-endothelial barrier due to a SARS-CoV-2 infection probably promotes the expression of a Pasteurella infection. In addition, the SARS-CoV-2 infection induced immunosuppression, and an inflammatory cascade could explain the infection's severity. The use of corticosteroids, which are part of the first-line therapeutic arsenal against COVID-19, may also promote the pathogenicity of this agent.

Seroprevalence of chikungunya virus infection among HIV-infected adults in French Caribbean Islands of Martinique and Guadeloupe in 2015: A cross-sectional study.

BACKGROUND: In 2014, a first outbreak of chikungunya hit the Caribbean area where chikungunya virus (CHIKV) had never circulated before. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study to measure the seroprevalence of CHIKV immediately after the end of the 2014 outbreak in HIV-infected people followed up in two clinical cohorts at the University hospitals of Guadeloupe and Martinique. Study patients were identified during the first months of 2015 and randomly selected to match the age and sex distribution of the general population in the two islands. They were invited to complete a survey that explored the symptoms consistent with chikungunya they could have developed during 2014 and to have a blood sample drawn for CHIKV serology. The study population consisted of 377 patients (198 in Martinique and 179 in Guadeloupe, 178 men and 199 women), 182 of whom reported they had developed symptoms consistent with chikungunya. CHIKV serology was positive in 230 patients, which accounted for an overall seroprevalence rate of 61% [95%CI 56-66], with only 153 patients who reported symptoms consistent with chikungunya. Most frequent symptoms included arthralgia (94.1%), fever (73.2%), myalgia (53.6%), headache (45.8%), and skin rash (26.1%). CONCLUSIONS/SIGNIFICANCE: This study showed that the seroprevalence of CHIKV infection was 61% after the 2014 outbreak, with one third of asymptomatic infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02553369.

Contribution of Research in the West Indies and Northeast Amazonia to Knowledge of the 2014-2015 Chikungunya Epidemic in the Americas.

PURPOSE OF REVIEW: Although the chikungunya virus was discovered more than 60 years ago, it has only really been studied since the outbreak in La Reunion in 2005-2006. Ten years later, between 2014 and 2015, the chikungunya virus spread throughout the Americas, affecting millions of people. The objective of this review is to describe the contributions of research on chikungunya virus infection gained from epidemic in the West Indies and the Guiana Shield. RECENT FINDINGS: Prevalence data were similar to those found in the Indian Ocean or Asia during epidemics. Clinically, there is now a better understanding of the typical, atypical, and severe forms. Several studies have insisted on the presence of neurological forms of chikungunya infection, such as encephalitis or Guillain-Barré syndrome. Cases of septic shock due to chikungunya virus as well as thrombotic thrombocytopenic purpura were described for the first time. Given the magnitude of the epidemic and the large number of people affected, this has led to a better description and new classifications of chikungunya virus infections in specific populations such as pregnant women, the elderly, and children. Several studies also described the behavior of populations faced with an emerging disease. SUMMARY: Current epidemiological data from tropical regions highlights the risk of spreading emerging diseases at higher latitudes, especially concerning arboviruses, since the vector Aedes albopictus is already established in many parts of northern countries. A better understanding of the disease and its epidemic dynamics will foster better management, the crucial importance of which was demonstrated during the COVID-19 epidemic.

Genotype distribution of cervical HPV among Caribbean women in a population-based study in Martinique: The DEPIPAPUFR study.

The Caribbean ranks seventh among the world regions most affected by cervical cancer. HPV-prevalence and genotype distributions also differ from regions. Knowledge of HPV genotype profiles is important for patients care and HPV vaccination implementation. The objective of this study was to describe HPV genotype distribution and risk factors in a population-based cohort of women in Martinique. In this study, 1312 women were included and underwent cervical cancer screening with successful sample collection between 2009 and 2014. Sociodemographic and clinical variables were recorded. Cytological examination of cervical vaginal smear was performed and classified(Bethesda). Detection of HPV DNA was performed with the PapilloCheck© Kit from Greiner Bio-one. Genotypes were analyzed for18 high-risk HPV (hrHPV) and 6low-risk HPV(lrHPV) types. A total of 1075 women were included with a mean age of 49.1±10.5 years. HPV prevalence was 27.6% (297/1075) with 19.4% (209/1075) women with only hrHPV, 5.3% (57/1075) with only lrHPV. Multiple infections (hrHPV/lrHPV) were detected in 31/240 cases of hrHPV (12.9%). A total of 353 hrHPV genotypes were analyzed; the most common HPV types were HPV51 (11.0%), HPV68 (10.8%), HPV53 (9.1%) and HPV 52 (7.1%). HPV16 and HPV18 represented respectively 4.8% and 4.0% of hrHPV genotypes. Abnormal cytology was observed in 34 cases (3.2%), with 14 ASCUS (1.3%), 10 LSIL (0.9%), 5 HSIL (0.5%), 3 ASC-H (0.3%) and 2 AGC (0.2%). Fifteen (44.1%) were hrHPV and 4 (14.7%) lrHPV; 7 cases of hrPHV were in the age-group 25-34 years. Among 1041cases of normal cytology, 225 had positive hrHPV detection (21.6%). This is the first population-based study of HPV profiles in our country, and we found a high prevalence of hrHPV. The most common genotypes were HPV51, 68, 53. These results could serve for cancer vaccination strategies and HPV surveillance in Martinique.

Reemergence of syphilis in Martinique, 2001-2008.

Syphilis reemerged in Martinique in 2004 and initially affected 3 HIV-infected patients. By March 2008, syphilis was diagnosed for 37 men and 18 women. As of October 31, 2009, this outbreak had not yet been brought under control. It initially affected mainly men who had sex with men before it spread to heterosexual persons, minority group members, and crack cocaine users.

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique): A prospective cohort study.

BACKGROUND: The chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity. METHODOLOGY/PRINCIPAL FINDINGS: A total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4-32.2, p = 0.04). CONCLUSIONS: This cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders. TRIAL REGISTRATION: clinicaltrials.gov (NCT01099852).

The effects of chikungunya virus infection on people living with HIV during the 2014 Martinique outbreak.

Our objective was to describe the clinical presentation of chikungunya virus (CHIKV) infection in patients living with HIV (PLHIV) during the 2014 Martinique outbreak. During the outbreak and the 6 following months, all PLHIV coming in our unit for a medical evaluation answered questions about potential CHIKV related symptoms, and had blood tests to assess the diagnosis. For patients coming in at the acute phase of infection, we are able to provide and analyze CD4+, CD8+ T-cells and HIV viral load evolution before, during and after CHIK infection. Among the 1 003 PLHIV in care in the center at the time of the outbreak, 188 (94 men and 94 women) had confirmed (following the WHO definition) CHIKV infection. Clinical presentation was common in 63% of the cases, severe and atypical forms were scarce. During the acute phase, CD4+ and CD8+ T-cells (evaluated in 30 PLHIV, 15 men and 15 women) absolute numbers dropped significantly, but returned to pre-CHIKV values after the acute phase. Reassuringly, CD4 and CD8 T cells proportions did not decrease during the acute phase. CHIKV infection had no significant impact on this anti-retroviral treated population.

Prospective observational study of low thresholds for platelet transfusion in adult dengue patients.

BACKGROUND: The practice of platelet (PLT) transfusions has been adopted into the standard clinical practice in many dengue-endemic countries. Because many patients were found to have received unnecessary PLT transfusions, the development of guidelines for the management of dengue patients with thrombocytopenia has become a necessity. STUDY DESIGN AND METHODS: An emergency department-based prospective observational study was conducted in Martinique during a dengue outbreak in adult patients presenting with an acute febrile illness. Patients with severe bleeding and/or who underwent invasive intensive care procedures or emergency surgery were given PLT transfusion to achieve PLT counts of more than 50 x 10(9)/L. PLT transfusion was also considered for patients with PLT counts of less than 5 x 10(9)/L and for those with associated risk factors and PLT counts of less than 20 x 10(9)/L. RESULTS: A total of 350 patients were admitted with confirmed dengue infections. Most of them had secondary serotype-2 infections. PLT counts of less than 50 x 10(9)/L were recorded in 165 patients (47.1%). PLT transfusion was administered to 9 patients with thrombocytopenia. The indications included severe bleeding (5 cases), invasive procedures (3 cases), emergency surgery (1 case), and/or associated risk factors (2 cases). The median time duration from the onset of fever to PLT transfusion was 6 days (range, 4-10 days). The median amount of PLTs transfused was 3.66 x 10(11) (range, 2.8 x 10(11)-13.2 x 10(11)). The median PLT yield was +12.4% (range, -3.9% to +67.1%). Three patients died. All other patients recovered during the second week after the onset of fever. CONCLUSION: A restrictive strategy for PLT transfusion based on clinical features and low PLT count thresholds proved to be feasible and safe for adult dengue patients.

Anicteric cholestasis among HIV infected patients with syphilis.

In Martinique, among 9 HIV carriers recently diagnosed with early syphilis, 7 had biologic cholestasis. Less than half of the patients had been diagnosed on clinical grounds for syphilis (cutaneous eruption or syphilis in partner), whereas most of them were diagnosed on a systematic screening of HIV infected patients.

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.

Reaching the WHO target of testing persons in jails in prisons will need diverse efforts and resources.

BACKGROUND: The Caribbean is the second most affected region in the world by human immunodeficiency virus (HIV), and HIV prevalence is significantly higher among persons in jails and prisons than in the free population. The aim of our study was to assess the screening rates of HIV, hepatitis B and C, syphilis and human T cell leukaemia virus type 1 among newly-arrived persons in 2014, at Ducos facility in Martinique and the testing process performance. METHODS: This is an observational monocentric study conducted within the prison's health unit. The study population consisted of all individuals incarcerated between 01/01/14 and 31/12/14. At the initial medical visit, HIV and STI testing were proposed to every newcomer. The rate of acceptance was calculated, as well as the screening process performance. RESULTS: In 2014 778 new persons were incarcerated, among those, 461 (59.3%) were tested. The main reasons for missing the testing opportunity were due to organization of the judiciary system (persons on electronic monitoring or day parole, transferred or quickly released before completion of the process) or to individual refusal. Finally, 75 persons did not get their results (all of them negative), 41 of them due to the medical staff work overload. CONCLUSIONS: HIV and STI testing rates among newcomers at Ducos have notable room for improvement. The future availability of combined (HIV, HBV, HCV and syphilis) rapid tests may be very useful in case of short term incarceration, if their cost is not prohibitive. Reaching higher levels of testing will also require more resources.

Occurrence of Chronic Stage Chikungunya in the General Population of Martinique during the First 2014 Epidemic: A Prospective Epidemiological Study.

Chronic stage chikungunya (CHIK), defined by persisting symptoms more than 3 months after initial diagnosis of acute infection, is frequent. However, its burden and impact have rarely been described prospectively in a general population during an ongoing epidemic in the Caribbean. From January 2014 to January 2015, a severe CHIK outbreak occurred in Martinique. Our objective was to describe epidemiological characteristics and outcomes of chronic stage CHIK in its local population. Participants, clinically diagnosed with probable CHIK infection, were included prospectively by general practitioners during the epidemic's peak from April to October 2014. All identified cases benefited from a follow-up phone call 3 months or more after initial diagnosis during which they were interrogated about persisting clinical signs, past and ongoing treatment, and quality of life. Five hundred and nine subjects participated in the study. Mean age at initial diagnosis was 43.2 ± 23.6 years with a female-male ratio of 1.98. Two hundred participants (39.3%) had probable chronic stage CHIK: 98.5% still experienced pain at least 3 months after acute infection, with 84.3% of reported joint pains; 21.2% were woken up by the pain; 47.2% felt depressed/anxious; and 31.3% experienced memory/concentration disorders. Resumption of daily activity and work was complicated for 55.8% and 36.2% of cases. Persistent impact on morbidity, health outcomes, psychological, and economic aspects further underline the crucial role of community-based medicine and the necessity of an evidence-based multidisciplinary approach toward chronic stage CHIK identification, management, and follow-up in this particular world region.