Weight gain during the dolutegravir transition in the African Cohort Study

IntroductionDolutegravir (DTG) has become a preferred component of first‐line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single‐tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries.MethodsThe African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist‐to‐hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m². Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist‐to‐hip ratio.ResultsFrom 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22–2.55) compared to PLWH on non‐TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32–1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25–0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18–1.75) in the year following transition to TLD after adjustment for confounders.ConclusionsElevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow‐up after transitioning to TLD.     

Weight changes after antiretroviral therapy initiation in CoRIS (Spain): a prospective multicentre cohort study

IntroductionWeight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV‐positive individuals.MethodsThis was a prospective cohort study of 13,198 subjects included in the Spanish HIV Research Network (CoRIS) between January 2004 and November 2018. We included subjects who started triple ART and achieved HIV RNA suppression within 48 weeks. We fitted linear mixed models adjusted for potential confounders to compare longitudinal changes in weight. We used Cox proportional‐hazard models to compare treatment groups’ times to transition to a higher body mass index (BMI) category.ResultsWe analysed data from a total of 1631 individuals resulting in 14,965 persons/years and 14,085 observations. Individuals retained in the final multivariable model were representative of the overall cohort. NNRTI‐based first‐line ART was associated with a lower average weight gain compared to PI‐ (+0.7 kg per year, 95% CI 0.5 to 1.0, p < 0.001) and INSTI‐based (+0.9 kg per year, 95% CI 0.7 to 1.1, p < 0.001) regimens. Individuals starting ART with TAF+FTC had greater weight gain than those receiving TDF+FTC (+0.8 kg per year, 95% CI 0.3 to 1.4, p = 0.004). Women and black persons presented a greater weight gain than men and non‐black individuals. Differences in weight trajectories were driven mainly by changes during the first year of ART. The NNRTI group was less likely to transition from normal weight to overweight than the PI (aHR 1.48, 95% CI 1.18 to 1.85) and INSTI groups (aHR 1.30, 95% CI 1.03 to 1.64). PIs but not INSTIs were associated with a higher rate of overweight‐to‐obesity shift (aHR 2.17, 95% CI 1.27 to 3.72). No differences were found among INSTIs in the transition to a higher BMI category.ConclusionsINSTI‐ and PI‐based first‐line ARTs are associated with greater weight gain compared to NNRTI‐based ART. Within the NRTIs, TAF+FTC was most strongly associated with weight gain. This heterogeneous effect of ART on body weight could affect the long‐term risk of some non‐communicable diseases.     

Incidence and mortality of tuberculosis before and after initiation of antiretroviral therapy: an HIV cohort study in India

Introduction

India has the highest burden of tuberculosis (TB) in the world, but the epidemiology of HIV-associated TB is not well known.

Methods

We describe the incidence and the mortality of TB from HIV diagnosis to antiretroviral therapy (ART) initiation (pre-ART group) and after ART initiation (on-ART group) in an HIV cohort study in Anantapur, India. Multivariable analysis of factors associated with TB was performed using competing risk regression and restricted cubic spline methods.

Results

A total of 4590 patients and 3133 person-years (py) of follow-up were included in the pre-ART group, and 3784 patients and 4756 py were included in the on-ART group. In the pre-ART group, the incidence of TB was high during the first month after HIV diagnosis and dropped nearly four times soon after. In the on-ART group, the incidence of TB increased after ART initiation reaching a peak in the third month. The probability of having TB within 30 months was 22.3% (95% confidence interval [CI], 21.1–23.6) in the pre-ART group and 17.8% (95% CI, 16.3–19.3) in the on-ART group. In a multivariable analysis, women had a lower risk of TB in both groups. Poor socio-economical conditions were associated with an increased risk of TB in the pre-ART group, but not in the group on-ART. While the association between low CD4 counts and TB was strong in the pre-ART group, this association was weaker in the on-ART group, and the highest risk of TB was seen in those patients with CD4 counts around 110 cells/mm³. The cumulative incidence of mortality at 12 months in patients with TB was 29.6% (95% CI, 26.9–32.6) in pre-ART TB and 34.9% (95% CI, 31–39.1) in on-ART TB. Half deaths before ART initiation and two thirds of deaths after ART initiation occurred in patients with TB.

Conclusions

The high incidence and mortality of TB seen in this study underscore the urgent need to improve the prevention and diagnosis of HIV-associated TB in India. We found substantial differences between TB before and after ART initiation.     

Weight loss and effect on co-morbidities in the long-term after duodenal switch and gastric bypass: a population-based cohort study

BackgroundUnsatisfactory weight loss is common after bariatric surgery in patients with super obesity (body mass index [BMI] ≥50 kg/m²). Unfortunately, this group of patients is increasing worldwide.ObjectiveThe aim of this study was to compare long-term weight loss and effect on co-morbidities after duodenal switch (DS) and gastric bypass (RYGB) in super-obese patients.SettingUniversity hospital, Sweden, national cohort.MethodsThis observational population-based cohort-study of primary DS and RYGB (BMI ≥48 kg/m²) in Sweden from 2007 to 2017 used data from 4 national registers. Baseline characteristics were used for propensity score matching (1 DS:4 RYGB). Weight loss was analyzed up until 5 years after surgery. Medication for diabetes, hypertension, dyslipidemia, depression, and pain were analyzed up until 10 years after surgery.ResultsThe study population consisted of 333 DS and 1332 RYGB, with 60.7% females averaging 38.5 years old and BMI 55.0 kg/m² at baseline. DS resulted in a lower BMI at 5 years compared with RYGB, 32.2 ± 5.5 and 37.8 ± 7.3, respectively, (P < .01). DS reduced prevalence of diabetes and hypertension more than RYGB, while reduction in dyslipidemia was similar for both groups, during the 10-year follow-up. Both groups increased their use of antidepressants and a maintained a high use of opioids.ConclusionThis study indicates that super-obese patients have more favorable outcomes regarding weight loss and effect on diabetes and hypertension, after DS compared with RYGB.     

Outcomes of endoscopic treatment of leaks and fistulae after sleeve gastrectomy: results from a large multicenter U.S. cohort

BackgroundSleeve gastrectomy is the most commonly performed bariatric surgery in the United States. Leaks after sleeve gastrectomy (SGL) occur in 1% to 3% of patients. Endoscopic therapies are increasingly used for treatment of SGLs, but few data exist on their outcomes.ObjectivesThe aim of this study was to assess technical success, leak resolution, and reoperation rates of patients undergoing endoscopic therapy for repair SGLs.SettingEight high-volume academic endoscopy centers.MethodsPatients undergoing endoscopic therapy for SGLs from 2007 to 2017 were identified. Patients were excluded if the index endoscopic therapy for SGL was performed elsewhere or if no follow-up data were available. Leaks were classified as acute (≤7 d of SG), early (1–6 wk), late (7–12 wk), and chronic (>12 wk). Leak resolution was defined as lack of extraluminal air, extravasation on oral contrast radiography, cross-sectional imaging, or resolution of percutaneous drain output. Demographic and procedural data were recorded as rates of additional therapy, adverse events, and surgical revision.ResultsA total of 85 patients met criteria for analysis (70 women, age 42.6 ± 10.8 yr). A total of 295 endoscopic sessions (median 3, range 1–14) were performed across the cohort. SGLs resolved after index endoscopic therapy in 43 (50.1%) patients. The primary outcome of endoscopic resolution of SGL was observed in 62 patients (72.9%). There were 34 (11.5%) PRAE (the majority occurring with self-expandable metal stents), all but 1 of which were managed endoscopically. Surgical revision was required in 23 (21.7%) patients. On univariate analyses independent variables associated with the need for surgical revision included both acute and chronic SGLs (P = .028), loculated subphrenic collections/abscesses (P = .03), and intraabdominal sepsis (P = .03). On multivariable logistic regression using statistically significant predictors from the univariate analyses, acute SGLs were significantly associated with a need for surgical revision (odds ratio 4.8, 95% confidence interval 1.2–18.9, P = .025).ConclusionEndoscopic therapy for SGLs is associated with good clinical success, avoiding the need for surgical revision in 73% of patients, with an acceptable adverse event profile. Patients with acute or chronic SGLs and those with loculated abscesses or intraabdominal sepsis are more likely to undergo surgical revision. Endoscopic therapy is an appropriate first-line modality for the management of SGLs, especially those not classified as acute or chronic.     

Virologic non‐suppression and early loss to follow up among pregnant and non‐pregnant adolescents aged 15–19 years initiating antiretroviral therapy in South Africa: a retrospective cohort study

IntroductionOlder adolescents aged 15–19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non‐suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa.MethodsWe included adolescents aged 15–19 years initiating ART between 2004 and 2019, with ≥ one viral load (VL) measurement between 4 and 24.5 months, and ≥ 6 months follow‐up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS‐Southern Africa (IeDEA‐SA). We defined VNS as VL ≥400 copies/ml and LTFU as not being in care for ≥180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART. We examined factors associated with VNS and LTFU using Fine&Gray competing risk models.ResultsWe included a total of 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24‐month follow‐up, 424 (15.5%) of all adolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/μl at ART initiation among all adolescents having adjusted for all measured patient characteristics [adjusted sub‐distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. ≤200 cells/μl: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/μl were risk factors for LTFU among all adolescents.ConclusionsOlder adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent‐friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified.     

Elective surgery for diverticular disease in U.S. veterans: A VASQIP study of national trends and outcomes from 2004 to 2018

BackgroundTreatment for diverticular disease has evolved over time. In the United States, there has been a trend towards minimally invasive surgical approaches and fewer postoperative complications, but no study has investigated this subject in the Veterans Health Administration.MethodsThis retrospective review identified patients undergoing elective surgery for diverticular disease from 2004 to 2018. Demographics, comorbidities, operative approach, rates of ostomy creation, and 30-day outcomes were compared. The 15-year time period was divided into 3-year increments to assess changes over time.Results4198 patients were identified. Complication rate decreased significantly over time (28.1%–15.7%, p < 0.001), as did infectious complications (21.5–6.3%, p < 0.001). Median hospital length-of-stay decreased from 7 to 5 days (p < 0.001). Rates of laparoscopic surgery increased over time (17.7%–48.1%, p < 0.001).ConclusionsIncreased utilization of laparoscopy in veterans undergoing elective surgery for diverticular disease coincided with fewer complications and a shorter length-of-stay. These trends mirror outcomes reported in non-veterans.