Emergence of acquired dolutegravir resistance in treatment-experienced people with HIV in Lesotho.

BACKGROUND: Since 2019, the World Health Organization has recommended dolutegravir-based antiretroviral therapy (ART) as the preferred regimen for HIV management. Large-scale programmatic transitioning to dolutegravir-based ART was subsequently implemented across Africa, often in the absence of recent viral load testing and without access to genotypic resistance testing (GRT) in case of viremia. METHODS: This study assessed for emerging dolutegravir resistance in the routine care Viral Load Cohort North-East Lesotho (VICONEL). We included pediatric and adult participants who changed from non-nucleoside transcriptase inhibitor- (NNRTI-) to dolutegravir-based ART and had at least one viral load assessment before and after the change. We sequenced available samples of participants fulfilling the additional virological criteria of having two viraemic episodes while taking dolutegravir, thereof at least one viral load ≥500 copies/mL taken ≥18 months after changing to dolutegravir. RESULTS: Among 15'349 participants, 157 (1.0%) met the virological criteria and GRT was successful for 85 (0.6%). Among these 85, eight (9.4%) had dolutegravir resistance, with two (2.4%) and six (7.1%) predicted to have intermediate and high-level dolutegravir resistance, respectively. One participant had two, two had one, and five had zero active drugs in their regimen. A GRT from before the change to dolutegravir is available for five of these eight participants: four had zero and one had one active drug in their NNRTI-based regimen. CONCLUSIONS: Nine percent of people with persistent or recurring HIV viremia ≥18 months after changing to dolutegravir-based ART had dolutegravir resistance. Detection and management of emerging dolutegravir resistance must be addressed across Africa.

Final 3-Year Study Outcomes from the Evaluation of the Zilver Vena Venous Stent for the Treatment of Symptomatic Iliofemoral Venous Outflow Obstruction (The VIVO Clinical Study).

PURPOSE: To report 3-year outcomes from a prospective, multicenter, nonrandomized, single-arm study designed to assess the safety and effectiveness of the Zilver Vena Venous Stent for the treatment of symptomatic iliofemoral venous outflow obstruction. MATERIALS AND METHODS: The VIVO study included patients with symptomatic obstruction of 1 iliofemoral venous segment (ie, 1 limb), characterized by a Clinical, Etiological, Anatomic, Pathophysiology (CEAP) clinical classification of ≥3 or a Venous Clinical Severity Score (VCSS) for pain of ≥2. Patients were retrospectively grouped based on baseline clinical presentation as postthrombotic syndrome (PTS), nonthrombotic iliac vein (NIVL) obstruction, or acute deep vein thrombosis (aDVT). Clinical improvement was assessed by change in VCSS, Venous Disability Score, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) scores, and CEAP C classification. Stent performance was evaluated by rates of patency by ultrasound (US), freedom from clinically driven reintervention, and freedom from stent fracture. RESULTS: The 3-year results for the 243 patients in the VIVO cohort included a 90.3% rate of patency by US and a 92.6% rate of freedom from clinically driven reintervention. The 3-year rates of patency by US for the NIVL, aDVT, and PTS groups were 100%, 84.0%, and 86.1%, respectively. Sustained clinical improvement through 3 years was demonstrated by changes in VCSS, Venous Disability Score, CIVIQ-20, and CEAP C classification. No stent fractures were observed. CONCLUSIONS: The VIVO study demonstrated sustained high rates of patency and freedom from clinically driven reintervention and improvements in venous clinical symptoms through 3 years. Each patient group (NIVL, aDVT, and PTS) showed clinical improvement and sustained patency through 3 years; some variation existed among groups (eg, only the NIVL group had a 100% patency rate).

Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity.

BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV). METHODS: Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2 and between older age or obesity and the immunoglobulin G response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.

Two-Year Outcomes of Treatment-Experienced Adults After Programmatic Transitioning to Dolutegravir: Longitudinal Data From the VICONEL Human Immunodeficiency Virus Cohort in Lesotho.

In the Viral Load Cohort North-East Lesotho (VICONEL) human immunodeficiency virus cohort, 14 242 adults had transitioned from efavirenz- or nevirapine-based antiretroviral therapy (ART) to dolutegravir-based ART by October 2021. Rates of viral suppression to <50 copies/mL were 84.8%, 93.9%, and 95.4% before, 12 months after, and 24 months after transition, respectively. Sex, age, pretransition viral load, and treatment backbone correlated with 24-month viremia.

Probable Transmission of SARS-CoV-2 from African Lion to Zoo Employees, Indiana, USA, 2021.

We describe animal-to-human transmission of SARS-CoV-2 in a zoo setting in Indiana, USA. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after onset of respiratory signs. Zoo employees were screened, monitored prospectively for onset of symptoms, then rescreened as indicated; results were confirmed by using reverse transcription PCR and whole-genome virus sequencing when possible. Traceback investigation narrowed the source of infection to 1 of 6 persons. Three exposed employees subsequently had onset of symptoms, 2 with viral genomes identical to the lion's. Forward contact tracing investigation confirmed probable lion-to-human transmission. Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods for big cats and other susceptible animals should be developed and validated to enable timely implementation of One Health investigations.

Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho.

INTRODUCTION: HIV programmes across many countries in Africa have recently transitioned people living with HIV from efavirenz (EFV)- to dolutegravir (DTG)-containing antiretroviral therapy (ART). As both drugs are associated with neuropsychiatric adverse effects, this study assessed the mental health and HIV/ART-associated symptoms of people living with HIV before and after transition to DTG. METHODS: The prospective DO-REAL cohort enrolled people starting DTG-based ART in Lesotho from February to December 2020. For this analysis within DO-REAL, we included adults changing from tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/EFV to TDF/3TC/DTG within first-line therapy. At transition and 16 weeks thereafter, participants completed the Patient Health Questionnaire-9 (PHQ-9; depression screening), the 12-item Short-Form Health Survey (SF-12; mental and physical health), and a modified HIV Symptom Index (mHSI; HIV/ART-related symptoms). We also assessed weight change. We used McNemar tests with Bonferroni corrections to assess binary outcomes. CLINICALTRIALS: gov: NCT04238767. RESULTS: Among 1228 participants, 1131 completed follow-up. Of these, 60.0% were female, the median age was 46 years (interquartile range [IQR] 38-55), and the median time taking ART was 5.7 years (IQR 3.5-8.9). No change was observed for weight or overall PHQ-9 or SF-12 outcomes. However, three mHSI items decreased at follow-up: 'feeling sad/down/depressed' (bothered 6.0% vs. 3.3% of participants at least 'a little' before vs. after transition; adjusted p = 0.048); 'feeling nervous/anxious' (7.4% vs. 3.4%; adjusted p = 0.0009); and 'nightmares, strange/vivid dreams' (6.3% vs. 3.5%; adjusted p = 0.027). Individual PHQ-9 or SF-12 items also improved. Being symptom free across all measures increased from 5.1% to 11.4% (p < 0.0001). CONCLUSIONS: We observed no negative impacts and potential moderate improvements with DTG, providing further support for the rollout of DTG.

Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study).

OBJECTIVES: Since 2018, the World Health Organization has recommended dolutegravir (DTG)-containing antiretroviral therapy (ART) for most people living with HIV. Country programmes across Africa have subsequently transitioned from other, mostly nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART to DTG-based ART. This study aims to assess the virological impact of programmatic transitioning to DTG-based ART in Lesotho. METHODS: The prospective Dolutegravir in Real-Life in Lesotho (DO-REAL) cohort enrols people living with HIV initiating or transitioning to DTG-based ART in Lesotho. Here, we present data from participants who transitioned from NNRTI- to DTG-based ART between February and December 2020. Blood samples collected at transition and at 16 weeks' follow-up (window 8-32 weeks) were used for viral load (VL) and resistance testing. RESULTS: Among 1347 participants, follow-up data was available for 1225. The majority (60%) were female, median age at transition was 47 years [interquartile range (IQR): 38-56], and median (IQR) time since ART initiation was 5.9 (3.5-9.0) years. Among those with complete VL data, the rate of viral suppression to < 100 copies/mL was 1093/1116 (98%) before, 1073/1116 (96%) at, and 1098/1116 (98%) after transition. Even among those with a VL ≥ 100 copies/mL at transition, 42/44 (95%) achieved suppression to < 100 copies/mL at follow-up. Seven participants had a VL ≥ 1000 copies/mL at follow-up and did not harbour any integrase mutations associated with resistance to DTG. CONCLUSIONS: The high levels of viral suppression observed are encouraging regarding virological outcomes upon programmatic transitioning from NNRTI- to DTG-based ART.

Orthopoxvirus Testing Challenges for Persons in Populations at Low Risk or Without Known Epidemiologic Link to Monkeypox - United States, 2022.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

Powassan Virus Infection Likely Acquired Through Blood Transfusion Presenting as Encephalitis in a Kidney Transplant Recipient.

A kidney transplant patient without known tick exposure developed encephalitis 3 weeks after transplantation. During the transplant hospitalization, the patient had received a blood transfusion from an asymptomatic donor later discovered to have been infected with Powassan virus. Here, we describe a probable instance of transfusion-transmitted Powassan virus infection.

Reduced white matter microstructure in bipolar disorder with and without psychosis.

OBJECTIVES: Affective and psychotic features overlap considerably in bipolar I disorder, complicating efforts to determine its etiology and develop targeted treatments. In order to clarify whether mechanisms are similar or divergent for bipolar disorder with psychosis (BDP) and bipolar disorder with no psychosis (BDNP), neurobiological profiles for both the groups must first be established. This study examines white matter structure in the BDP and BDNP groups, in an effort to identify portions of white matter that may differ between the bipolar and healthy groups or between the bipolar subgroups themselves. METHODS: Diffusion-weighted imaging data were acquired from participants with BDP (n = 45), BDNP (n = 40), and healthy comparisons (HC) (n = 66). Fractional anisotropy (FA), radial diffusivity (RD), and spin distribution function (SDF) values indexing white matter diffusivity or spin density were calculated and compared between the groups. RESULTS: In comparisons between both the bipolar groups and HC, FA (FDR < 0.00001) and RD (FDR = 0.0037) differed minimally, in localized portions of the left cingulum and corpus callosum, while reductions in SDF (FDR = 0.0002) were more widespread. The bipolar subgroups did not differ from each other on FA, RD, or SDF metrics. CONCLUSIONS: Together, these results demonstrate a novel profile of white matter differences in bipolar disorder and suggest that this white matter pathology is associated with the affective disturbance common to those with bipolar disorder rather than the psychotic features unique to some. The white matter alterations identified in this study may provide substrates for future studies examining specific mechanisms that target affective domains of illness.

Impact of Caregiving During Emerging Adulthood on Frequent Mental Distress, Smoking, and Drinking Behaviors: United States, 2015-2017.

Objectives. To examine associations between caregiving mental or behavioral health outcomes among emerging US adults, defined as persons aged 18 to 25 years.Methods. The study sample included emerging adult respondents to the 2015-2017 Behavioral Risk Factor Surveillance System's caregiving module. Exposures were caregiver (n = 3087), expectant caregiver (n = 2303), and noncaregiver (n = 12 216) status. Expectant caregivers were defined as persons not currently providing care but anticipating doing so within the next 2 years. Outcomes included frequent mental distress (FMD), drinking (binge or heavy), and current smoking (cigarette or e-cigarette use). We used robust Poisson regression to calculate adjusted prevalence ratios (APRs) and corresponding 95% confidence intervals (CIs). We adjusted all models for income.Results. Caregivers had a similar prevalence of FMD when compared with both expectant caregivers (APR = 1.67; 95% CI = 1.28, 2.17) and noncaregivers (APR = 1.50; 95% CI = 1.23, 1.82). Caregivers had a higher prevalence of current cigarette smoking compared with noncaregivers (APR = 1.44; 95% CI = 1.21, 1.71).Conclusions. Among emerging adults, providing care is associated with poorer mental health. Point estimates looking at FMD were higher when we compared caregivers with expectant caregivers, suggesting a difference in exchangeability between comparison groups.Public Health Implications. This study highlights the importance of including emerging adults in caregiving research.

Patient Characteristics and Product Use Behaviors Among Persons with E-cigarette, or Vaping, Product Use-Associated Lung Injury - Indiana, June ̶ October 2019.

As of December 4, 2019, a total of 2,291 cases of hospitalized e-cigarette, or vaping, product use-associated lung injury (EVALI) have been reported from 50 states, the District of Columbia, and two U.S. territories (Puerto Rico and the U.S. Virgin Islands) (1). State health departments, including the Indiana State Department of Health (ISDH), are working with their local health departments and with CDC, the Food and Drug Administration, and other clinical and public health partners in investigating this outbreak of EVALI. On August 7, 2019, ISDH issued an advisory regarding patients hospitalized in Wisconsin with severe acute lung injury who reported the use of e-cigarette, or vaping, products (2); health care providers were requested to notify ISDH of similar cases. On August 8, 2019, ISDH received reports of five similar cases among Indiana residents. Suspected cases EVALI reported to ISDH were investigated further only among patients who required hospitalization. Established case definitions were used to classify cases.* Medical record abstractions and patient interviews were completed using nationally standardized forms to ascertain patient characteristics, medical care received, and product-use behaviors.

Hypothermia and Cold Weather Injuries.

Hypothermia, frostbite, and nonfreezing cold injuries predominantly affect older adults, homeless or intoxicated people, adventurers, and military personnel. Prevention begins with clothing that is clean, layered, and loose to promote circulation. Base layers made of moisture-wicking materials are favored over wool or cotton. Wool or fleece garments are ideal for middle layers, whereas outer layers should repel moisture. Hypothermia occurs when core body temperature drops below 95°F and can be staged by clinical symptoms when core temperature measurement is unavailable. Initial treatment includes external and internal rewarming. Warmed normal saline is favored over lactated Ringer solution. Frostbite is a freezing injury that usually affects the extremities. After rapid rewarming, prognosis is best determined with technetium 99mTc pyrophosphate scintigraphy or magnetic resonance angiography. Initial treatment includes protecting tissue from further trauma, preventing refreezing, and avoiding dry heat sources. Ideally, patients should be transported to facilities where rapid rewarming, imaging, and thrombolytic treatment are available. Tissue plasminogen activator significantly decreases amputation rates for severe injuries if started within 24 hours of rewarming. Immersion foot occurs during damp nonfreezing conditions. Rapid rewarming should be avoided, and amitriptyline should be considered for pain control.

The components of the adolescent brain and its unique sensitivity to sexually explicit material.

INTRODUCTION: The focus of this brief literature review is to explore whether there is a relationship between the unique anatomical and physiological paradigms of the adolescent brain and an increased sensitivity to sexually explicit material. METHODS: The EBSCO Research Data bases were searched using the following key terms: adolescence, adolescent brain development, neuroplasticity, sexually explicit material, sexualization, and pornography. RESULTS: The literature highlighted several components of the adolescent brain that are different than the mature brain. These include: an immature prefrontal cortex and over-responsive limbic and striatal circuits, heightened period for neuroplasticity, overactive dopamine system, a pronounced HPA axis, augmented levels of testosterone, and the unique impact of steroid hormones. The physiological response to sexually explicit material is delineated. The overlap of key areas associated with the unique adolescent brain development and sexually explicit material is noteworthy. A working model summary that compares the response of the adult and adolescent brain to the same sexually explicit stimulus is outlined. CONCLUSIONS: The literature suggests that the adolescent brain may indeed be more sensitive to sexually explicit material, but due to a lack of empirical studies this question cannot be answered definitively. Suggestions for future research are given to further advance the work in this applicable field of today.

Public Health Response to an Avian Influenza A(H7N8) Virus Outbreak in Commercial Turkey Flocks - Indiana, 2016.

In January 2016, highly pathogenic avian influenza (HPAI) A(H7N8) virus and low pathogenicity avian influenza (LPAI) A(H7N8) virus were detected in commercial turkey flocks in Dubois County, Indiana. The Indiana State Department of Health (ISDH) and the Dubois County Health Department (DCHD) coordinated the public health response to this outbreak, which was the first detection of HPAI A(H7N8) in any species (1). This response was the first to fully implement unpublished public health monitoring procedures for HPAI responders that were developed by the U.S. Department of Agriculture (USDA) and CDC in 2015 (Sonja Olsen, CDC, personal communication, October 2017). No cases of zoonotic avian influenza infection in humans were detected during the outbreak.

End-to-Side Versus Side-to-Side Jejunocecostomy in Horses: A Retrospective Analysis of 150 Cases.

OBJECTIVES: To determine factors associated with postoperative reflux, postoperative colic, repeat celiotomy, and survival in horses after end-to-side (E2S) or side-to-side (S2S) jejunocecostomy. STUDY DESIGN: Retrospective, multicenter study. SAMPLE POPULATION: Horses (n = 150). METHODS: Admissions, intra- and postoperative data were collected from medical records of horses that had E2S or S2S jejunocecostomy. Descriptive statistics were calculated and data were analyzed using parametric and nonparametric tests, linear and multivariate logistic regression with significance set at P < .05. Kaplan-Meier estimate of the survival function was performed. RESULTS: One hundred fifty horses (S2S = 90, E2S = 60) were included. S2S procedures were performed using staples (n = 57) or hand-sewn (33). Method of anastomosis was not significantly associated with development of postoperative reflux or colic, repeat celiotomy, whether the horse was alive at hospital discharge or 12 months after discharge. The number of years that the principal surgeon was boarded by the American College of Veterinary Surgeons significantly affected whether the horse was discharged from the hospital alive (P = .003). Age (P = .006) was significantly associated with 12-month survival. Increased age (P = .013) and administration of prokinetic medication (P = .0006) were significantly associated with development of postoperative reflux. Sixty-eight (76%) horses with S2S and 52 (87%) horses with E2S were discharged alive. CONCLUSION: Age, patient related variables, and surgeon experience may influence morbidity and mortality more than method of jejunocecostomy.

Social Communication and Parent Verbal Responsiveness Across Interaction Contexts in Toddlers on the Autism Spectrum.

PURPOSE: Interactions with caregivers during the ordinary activities that occur as families go about their everyday lives are critical to supporting children's acquisition of social communication and language skills. The purpose of this study was to examine child communication and parent verbal responsiveness across interaction contexts in 211 children (Mage = 20 months) on the autism spectrum (n = 121), with developmental delay (n = 46), or with typical development (n = 44). METHOD: Families participated in up to eight activities during an hour-long, video-recorded home observation. We tested differences in the strength of associations between diagnostic group and interaction context using linear mixed-effects models, with child rate per minute of communication and proportions of parent follow-in comments and directives as outcome variables. Child communicative functions expressed across contexts were also examined. RESULTS: Children across groups communicated at significantly higher rates per minute during book sharing and play with people compared to other interaction contexts. Most child communication was for the function of joint attention during book sharing, for social interaction during play with people, and for behavior regulation during necessary activities such as family chores and meals. On average, parents of children responded using proportionally more follow-in comments during book sharing and play compared to necessary activities, during which parents used more follow-in directives. CONCLUSION: Results provide a glimpse into the dyadic communication that may occur within everyday activities at home, which supports the need for future intervention research and may aid clinicians seeking to identify activities that serve as important contexts for intervention.

HIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study.

BACKGROUND: Treatment failure is common among children and adolescents with HIV. Antiretroviral therapy (ART) containing dolutegravir has recently been rolled out across Africa, though long-term real-world data in paediatric populations are lacking. Here, we report treatment outcomes among children and adolescents in Lesotho who transitioned from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir-based ART through 2 years' follow-up. METHODS: Data were derived from two open cohort studies in Lesotho. Children and adolescents aged less than 18 years who transitioned from NNRTI-based to dolutegravir-based ART at least 18 months before data closure were included. We report viral load results less than 12 months before, 12 (window: 6-17) months after, and 24 (window: 18-29) months after transition to dolutegravir. Associations of pretransition demographic and clinical factors with 24-month viraemia were assessed through multivariable logistic regression. RESULTS: Among 2126 included individuals, 1100 (51.7%) were female individuals, median age at transition to dolutegravir was 14.0 years [interquartile range (IQR) 11.5-15.8], and median time taking ART at transition was 7.6 years (IQR 4.4-10.6). Among those with a viral load result at the respective time points, viral suppression to less than 50 copies/ml was achieved by 1635 of 1973 (82.9%) less than 12 months before, 1846 of 2012 (91.8%) 12 months after, and 1725 of 1904 (90.6%) 24 months after transition to dolutegravir. Pretransition viraemia was associated with viraemia at 24 months, though more than 80% of individuals with pretransition viraemia achieved resuppression to less than 50 copies/ml at 24 months. CONCLUSION: The proportion of children and adolescents with viral suppression increased after transition to dolutegravir, though further progress is needed to reach global targets.

Clinical Relevance of Human Immunodeficiency Virus Low-level Viremia in the Dolutegravir era: Data From the Viral Load Cohort North-East Lesotho (VICONEL).

Background: Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however. Methods: We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (<50 copies/mL) and low- and high-range LLV (50-199 and 200-999 copies/mL, respectively) with virological failure (≥1000 copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group. Results: Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4-51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4-2.4 and dolutegravir: 2.1; 1.3-3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1-5.7 and 4.4; 2.4-7.9). Conclusions: In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL.