Transition times across the HIV care continuum in Spain from 2005 to 2022: a longitudinal cohort study.

BACKGROUND: Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. METHODS: We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. FINDINGS: We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. INTERPRETATION: The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. FUNDING: Instituto de Salud Carlos III and Spanish AIDS Research Network.

Bictegravir/emtricitabine/tenofovir alafenamide as first-line treatment in naïve HIV patients in a rapid-initiation model of care: BIC-NOW clinical trial.

OBJECTIVE: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. RESULTS: Two hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95 P = 0.49]) rates were very high over the 48- week study period. CONCLUSIONS: BIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.

Recently acquired hepatitis C: Epidemiological characteristics and treatment response in a large cohort of MSM living with HIV in Madrid.

INTRODUCTION: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain). METHODS: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded. RESULTS: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used. CONCLUSIONS: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%.

Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study.

Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.

Impact of COVID-19 on the Care of Patients with HIV Infection.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the "pandemic period" (March 2020 to February 2021), the "pre-pandemic period" (the equivalent time frame in 2019), and the "post-pandemic period" (March to September 2021). During the pandemic period, the number of new patients seen at the HIV clinic (116) as well as the requested viral load tests (2414) decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively) (p < 0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, and 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, and 93%, respectively), and the number of hospital admissions among PLWH remained constant. Despite the COVID-19 pandemic's impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates or all-cause mortality.

Management of Comorbidities in Treated HIV Infection: A Long Way to Go: HIV, comorbidities and aging.

Modern ART has now achieved the goal of maintaining HIV RNA suppression with minimum drug-related toxicities. Indeed, in high-income settings, the main health issues in adult people living with HIV (PLWH) today are diseases not directly associated with HIV. These conditions have become the central topic of discussion in HIV clinical forums. While they are common in the general population and typically associated with the aging process, their burden, diagnosis, clinical course and subsequent therapy alongside treated HIV infection exhibit specific features. Currently, we are confronted with the formidable challenge of normalizing the health of PLWH and creating a more comprehensive HIV management program. Here, we compile the opinions of a joint effort of 30 HIV specialists who reviewed the literature and debated the latest major challenges in the field of HIV-associated comorbidities and delineated future strategies to fully normalize health in HIV. Six key questions are answered and developed, such as the relevance of comorbidities in the management of HIV-infected patients, their drivers, management, prevention strategies, and possible evolution in the future.

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Hepatitis C and HIV combined screening in primary care: A cluster randomized trial.

Hepatitis C virus (HCV) and HIV are major causes of worldwide disease. We aimed to evaluate the effect of a combined screening programme, which included a risk-assessment questionnaire and rapid tests for point-of-care diagnosis, on screening and new diagnosis rates. This prospective, cluster randomized study was carried out in primary care. The intervention arm included a 4-hour educational programme, the use of a risk-assessment questionnaire and rapid tests. In the control centres, only the educational intervention was provided. The main variables compared were the screening coverage and the number and rate of new HCV and HIV diagnoses. Of a total of 7991 participants, 4670 (58.5%) and 2894 (36.2%) presented a risk questionnaire for HIV or HCV, respectively. The younger participants, men and those from Latin America and Eastern Europe, showed the greatest risk of presenting with a positive questionnaire. The overall screening coverage was higher within the intervention arm (OR 17.7; 95% CI 16.2-19.5; P < .001). Only two HIV-positives were identified compared to one in control centres. The rate of HCV diagnoses was higher among intervention centres, with 37 versus seven positive tests (OR 5.2; 95% CI 2.3-11.6; P < .001). Of them, 10 were new diagnoses and 27 had been previously diagnosed, although not linked to care. In conclusion, a simple operational programme can lead to an increase in HCV and HIV screening rates, compared to an exclusively educational programme. The selection of at-risk patients with a self-questionnaire and the use of rapid tests significantly increased the diagnostic rate of HCV infection.

Randomized Trial Evaluating the Neurotoxicity of Dolutegravir/Abacavir/Lamivudine and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: GESIDA 9016.

BACKGROUND: Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. METHODS: We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. RESULTS: Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. CONCLUSIONS: Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.

Maraviroc reactivates HIV with potency similar to that of other latency reversing drugs without inducing toxicity in CD8 T cells.

Human immunodeficiency virus (HIV) remains incurable due to latent reservoirs established in non-activated CD4 T cells. Current efforts to achieve a functional cure rely on immunomodulatory strategies focused on enhancing the functions of cytotoxic cells. Implementation of these actions requires a coordinated activation of the viral transcription in latently infected cells so that the reservoir became visible and accessible to cytotoxic cells. As no latency reversing agent (LRA) has been shown to be completely effective, new combinations are of increasing importance. Recent data have shown that maraviroc is a new LRA. In this work, we have explored how the combination of maraviroc with other LRAs influences on HIV reactivation using in vitro latency models as well as on the cell viability of CD8 T cells from ART-treated patients. Maraviroc reactivated HIV with a potency similar to other LRAs. Triple combinations resulted toxic and were rejected. No dual combination was synergistic. The combination with panobinostat or disulfiram maintained the effect of both drugs without inducing cell proliferation or toxicity. Maraviroc does not alter the viability of CD8 T cells isolated from patients under antiretroviral treatment. This finding enhances the properties of maraviroc as a LRA.

Impact of a structured HIV testing program in a hospital emergency department and a primary care center.

INTRODUCTION: HIV testing guidelines are poorly implemented in most clinical settings. The best screening strategy and healthcare scenario are still unknown. The aim of our study is to evaluate the impact of a structured HIV testing intervention (DRIVE), compared to HIV testing as routinely performed in clinical practice, in two different clinical settings: a primary care center and an emergency department. METHODS: Prospective evaluation of an HIV testing strategy in two clinical settings from the same healthcare area. The DRIVE program included trained nurse practitioners to perform the screening, a questionnaire to assess the risk of exposure and HIV indicator conditions (RE&IC), and rapid HIV tests. The main variables between the DRIVE program and clinical practice were the absolute number of newly diagnosed HIV infections and testing coverage. RESULTS: The DRIVE program included 5,329 participants, of which 51.2% reported at least one positive answer in the questionnaire. The estimated HIV testing coverage was significantly higher in the DRIVE program than in the routine clinical practice (7.17% vs. 0.96%, p < 0.001), and was better in the primary care center than in the emergency department with the two strategies. Twenty-two HIV-positive people were identified, with a rate of 8.6‰ in the emergency department vs. 2.2‰ in the primary care center (p = 0.001). A higher rate of new HIV diagnoses was found in the DRIVE program compared to routine clinical practice (29.6 vs. 3.1 per 100,000 patients attended; p < 0.001). CONCLUSIONS: An easy-to-implement, structured intervention increased the absolute number of new HIV diagnoses and HIV tests, compared to routine clinical practice.

Dolutegravir plus rilpivirine as dual regimen in virologically suppressed HIV-1 infected patients in a clinical setting.

Objectives: There are scarce data on the combination of dolutegravir (DTG) plus rilpivirine (RPV) in the real world, including patients with hepatitis C virus (HCV) coinfection, toxicity or previous failure, or at risk for severe drug-drug interactions (DDIs). Methods: Prospective cohort study of virologically suppressed HIV-1 infected patients, without resistance to DTG or RPV, switched to this dual regimen because of toxicity or risk of DDIs (NCT02491242). Results: Overall, 102 patients (mean age 54 years, 28% women) were included. Fifty-seven were coinfected with HCV (fibrosis grade 4 in 27 cases, 1 liver transplantation). Seven patients had chronic kidney disease (1 renal transplantation). At week 48, only 1 virologic failure occurred (<1%), and 6 patients (6%) left the regimen (3 with central nervous system adverse events, 1 each due to pregnancy, metformin interaction, and lost to follow up). Thus, the overall treatment success rates were 93% (95% CI, 88%-98%; ITT-e, snapshot analysis) and 96% (95% CI, 92%-99%; per protocol analysis). The CD4/CD8 ratio increased slightly (median, +0.03). Triglycerides levels improved significantly (-18.8%, p < 0.01). The creatinine-based estimated glomerular filtration rate decreased by a mean of -8.4 ml/min/1.73 m2, but tubular renal parameters improved. A paired dual X-ray absorptiometry scan showed a mild improvement in spine (mean, +1.15%; -0.57 to +3.3%) and in femoral neck bone mineral density (mean, +0.4%; -3.3% to +2.57%). Conclusions: In the clinical setting, switching to the combination of DTG plus rilpivirine in virologically suppressed HIV-1 patients is effective and safe, and improves lipid, renal and bone evolution.

Risk of cancer in HIV-infected patients in Spain, 2004-2015. The CoRIS cohort study. / Riesgo de cáncer en personas con VIH en España, 2004-2015. Estudio de la cohorte CoRIS.

INTRODUCTION: Cancer is a leading cause of death in individuals with HIV. METHODS: The incidence of cancer in HIV patients of the CoRIS cohort in the 2004-2009 and 2010-2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. RESULTS: Between January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51-781.42) with no significant differences between the 2periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010-2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21-0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13-14.17; females: 21.83, 2.66-47.79), non-Hodgkin's lymphoma in males (5.30, 2.86-8.45) and cervical cancer (7.43, 3.15-13.87) and head and neck cancer (3.28, 1.21-5.82) in women. CONCLUSIONS: The overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.

Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.

Sequential Chikungunya and Zika Virus Infections in a Traveler from Honduras.

Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized.