CardiOvaScular Mechanisms In Covid-19: methodology of a prospective observational multimodality imaging study (COSMIC-19 study).

BACKGROUND: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. METHODS: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA and 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. DISCUSSION: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION: This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at https://www.isrctn.com/ISRCTN12154994.

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases.

OBJECTIVE: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). BACKGROUND: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. METHODS: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. RESULTS: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. CONCLUSIONS: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Utilization of healthcare services among Chinese migrants in Kenya: a qualitative study.

BACKGROUND: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. METHODS: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. RESULTS: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. CONCLUSIONS: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial.

Importance: The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. Objective: To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and Participants: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. Interventions: Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and Measures: The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. Results: Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and Relevance: In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial Registration: ClinicalTrials.gov Identifier: NCT01298596.

Increased Cervical Human Immunodeficiency Virus (HIV) RNA Shedding Among HIV-Infected Women Randomized to Loop Electrosurgical Excision Procedure Compared to Cryotherapy for Cervical Intraepithelial Neoplasia 2/3.

Background: Treatment of human immunodeficiency virus (HIV)-infected women to prevent cervical cancer may stimulate HIV RNA cervical shedding and risk HIV transmission. Methods: From 2011 to 2014, 400 HIV-infected women diagnosed with cervical intraepithelial neoplasia 2/3 in Kenya were randomized to loop electrosurgical excision procedure (LEEP) or cryotherapy. Cervical samples were collected at baseline and 3 weekly intervals. Samples were tested for HIV RNA using the Gen-Probe Aptima HIV assay with a minimum detection level of 60 copies/swab and analyzed using generalized estimating equations. Results: Women who received LEEP had significantly higher cervical HIV RNA levels than those who received cryotherapy at weeks 2 (adjusted incident rate ratio [aIRR], 1.07; P = .038) and 3 (aIRR, 1.08; P = .046). Within LEEP, significantly higher cervical shedding was found at weeks 2 (2.03 log10 copies/swab; P < .001) and 3 (2.04 log10 copies/swab; P < .001) compared to baseline (1.80 log10 copies/swab). Cervical HIV RNA was significantly higher following LEEP for up to 3 weeks among women on antiretroviral treatment (ART) (0.18 log10 copies/swab increase; P = .003) and in ART-naive women (1.13 log10 copies/swab increase; P < .001) compared to baseline. Within cryotherapy, cervical shedding increased in ART-naive women (0.72 log10 copies/swab increase; P = 0.004) but did not increase in women on ART. Conclusions: Women randomized to LEEP had a larger increase in post-procedural cervical HIV shedding than cryotherapy. Benefits of cervical cancer prevention outweigh the risk of HIV sexual transmission; our findings underscore the importance of risk-reduction counseling. Clinical Trials Registration: NCT01298596.

Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug Resistance.

Healthcare delivery has advanced due to the implementation of point-of-care testing, which is often performed within minutes to hours in minimally equipped laboratories or at home. Technologic advances are leading to point-of-care kits that incorporate nucleic acid-based assays, including polymerase chain reaction, isothermal amplification, ligation, and hybridization reactions. As a limited number of single-nucleotide polymorphisms are associated with clinically significant human immunodeficiency virus (HIV) drug resistance, assays to detect these mutations have been developed. Early versions of these assays have been used in research. This review summarizes the principles underlying each assay and discusses strategic needs for their incorporation into the management of HIV infection.

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical Trials Registration: NCT01898754.

Alcohol use and immune reconstitution among HIV-infected patients on antiretroviral therapy in Nairobi, Kenya.

Studies on the effects of alcohol use on HIV disease progression have been contradictory, with at least one study finding a positive effect of low alcohol consumption on CD4 count. In addition, most such studies have taken place in the developed West. We investigated the association between alcohol use and immune reconstitution through CD4 count response among HIV-infected individuals on antiretroviral therapy (ART) at an urban sub-Saharan African clinic. This was a retrospective cohort study of treatment-naïve HIV-infected adults initiating ART in Nairobi, Kenya and followed for 12 months between January 2009 and December 2012. At enrollment, a standardized questionnaire was used to collect data on sociodemographic variables and alcohol consumption. CD4 count was measured every six months. Linear regression models assessed the association between CD4 count and alcohol consumption, categorized as abstinent, moderate, or hazardous. Overall, 854 participants were included, 522 of which were women, with 85 (25.6%) men and 50 (9.6%) women reporting any alcohol use, and 8 (2.4%) men and 7 (1.3%) women reporting hazardous drinking. At baseline, alcohol use was associated with higher education and socioeconomic status. Median CD4 count was higher among alcohol users compared to those who abstained at baseline and at 6 and 12 months post-ART initiation, although this was only significant at 6 months. There were no differences in adherence between abstainers and drinkers. While overall alcohol use was significantly associated with higher CD4 counts, moderate and hazardous use treated separately were not. We conclude that, while alcohol use was associated with higher CD4 counts at 12 months post-ART, the mechanism for this association is unclear but may reflect unmeasured socioeconomic or nutritional differences. Additional research is required on the specific drinking patterns of this population and the types of alcoholic beverages consumed to clarify this relationship.

Cost-effectiveness of cervical cancer screening and preventative cryotherapy at an HIV treatment clinic in Kenya.

OBJECTIVE: This study evaluated the potential cost-effectiveness of cervical cancer screening in HIV treatment clinics in Nairobi, Kenya. METHODS: A Markov model was used to project health outcomes and costs of cervical cancer screening and cryotherapy at an HIV clinic in Kenya using cryotherapy without screening, visual inspection with acetic acid (VIA), Papanicolaou smear (Pap), and testing for human papillomavirus (HPV). Direct and indirect medical and non-medical costs were examined from societal and clinic perspectives. RESULTS: Costs of cryotherapy, VIA, Pap, and HPV for women with CD4 200-500 cells/mL were $99, $196, $219, and $223 from a societal perspective and $19, $94, $124, and $113 from a clinic perspective, with 17.3, 17.1, 17.1, and 17.1 years of life expectancy, respectively. Women at higher CD4 counts (>500 cells/mL) given cryotherapy VIA, Pap, and HPV resulted in better life expectancies (19.9+ years) and lower cost (societal: $49, $99, $115, and $102; clinic: $13, $51, $71, and $56). VIA was less expensive than HPV unless HPV screening could be reduced to a single visit. CONCLUSIONS: Preventative cryotherapy was the least expensive strategy and resulted in highest projected life expectancy, while VIA was most cost-effective unless HPV could be reduced to a single visit.

Experiences and perceptions of online continuing professional development among clinicians in sub-Saharan Africa.

BACKGROUND: Limitations in healthcare worker (HCW) capacity compound the burden of dual TB and HIV epidemics in sub-Saharan Africa. To fill gaps in knowledge and skills, effective continuing profession development (CPD) initiatives are needed to support practicing HCWs reach high standards of care. e-learning opportunities can bring expert knowledge to HCWs in the field and provide a flexible learning option adaptable to local settings. Few studies provide insight into HCW experiences with online CPD in the developing country context. METHODS: An online survey using both close-ended and free response was conducted to HCWs in sub-Saharan Africa who completed the University of Washington (UW) School of Medicine online graduate course, "Clinical Management of HIV." Associations between respondent characteristics (age, gender, rural/urban, job title) and learning preferences, course barriers, and facilitators with an emphasis on online courses were examined using chi-square. Covariates significant at the p < 0.05 were analyzed using multivariable logistic regression. Responses to open-ended comments were analyzed using simplified grounded theory. RESULTS: Of 2,299 former students, 464 (20%) HCWs completed surveys from 13 countries: about half were women. Physicians (33%), nurses (27%), and clinical officers (30%) responded mostly from urban areas (67%) and public institutions (69%). Sixty-two percent accessed the online course from work, noting that slow (55%) or limited (41%) internet as well as lack of time (53%) were barriers to course completion. Women (p < 0.001) and HCWs under age 40 (p = 0.007) were more likely to prefer learning through mentorship than men or older HCWs. Respondents favored group discussion (46%), case studies (42%), and self-paced Internet/computer-based learning (39%) and clinical mentorship (37%) when asked to choose 3 preferred learning modalities. Free-response comments offered additional positive insights into the appeal of online courses by noting the knowledge gains, the flexibility of format, a desire for recognition of course completion, and a request for additional online coursework. CONCLUSIONS: Online CPD opportunities were accepted across a diverse group of HCWs from sub-Saharan Africa and should be expanded to provide more flexible opportunities for self-initiated learning; however, these need to be responsive to the limited resources of those who seek these courses.

Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya.

HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear.

Endoscope-Assisted Greater Occipital Nerve Decompression for Migraines, Occipital Neuralgia, and New Daily Persistent Headaches.

SUMMARY: In the occipital trigger site for migraine, the greater occipital nerve (GON) is thought to be irritated by surrounding structures, including the semispinalis capitis muscle and occipital artery (OA), producing headaches in the back of the neck. Thus, standard decompression involves removal of surrounding tissue and dissection away from the vessel. The authors noticed a consistent pattern between the GON and OA more distally: the OA approaching laterally and diving under the GON, the OA looping back over the GON and intertwining with the medial branch of the GON, and lastly the OA traveling parallel to the GON. The technique described uses a modified endoscopic approach with a counter incision, endoscopic assistance, and radical artery lysis to address distal sites in addition to the standard release. At the counter incision, distal intertwining between vessel and nerve was released. A high-definition endoscope was used to address dynamic compression points more proximally, including hidden areas where the vessel dives under the GON, as well as to facilitate cautery and removal of the vessel. Without the use of an endoscope and counterincision, it is difficult to achieve complete decompression of the nerve distally without injury to the proximal body of the nerve.

Performance of screening tools for cervical neoplasia among women in low- and middle-income countries: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the performance of visual inspection with acetic acid (VIA) testing, visual inspection with Lugol's iodine (VILI), primary HPV testing, and conventional Pap smear in detecting CIN2+ among non-pregnant women aged 30-65 in LMICs between 1990 and 2020. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Low- and middle-income countries, non-pregnant women aged 30-65. METHODS: CENTRAL (Cochrane Library), CINAHL, Embase, Global Health, PubMed, and Web of Science databases were systematically searched to identify studies evaluating the performance of cervical cancer screening methods in LMICs. A diagnostic test accuracy meta-analysis was conducted to evaluate the performance of 4 screening methods in detecting CIN2+ relative to biopsy or cytology reference standards. Pooled statistics for sensitivity, specificity, diagnostic odds ratios, and summary receiver operating characteristic curves were determined for each method. Subgroup analyses were performed to examine whether there was variation in performance based on different reference standards for defining CIN2+, specifically: colposcopy-directed biopsy, biopsy alone, colposcopy alone, or liquid-based cytology. RESULTS: Eighteen studies were identified through systematic review. Twelve studies were included in meta-analysis; 11 were cross-sectional and 1 was a randomized controlled clinical trial. The remaining six of the eighteen studies were inclided in a narrative syntehsis. Pooled estimates for sensitivity for VIA, VILI, primary HPV testing, and conventional Pap smear were 72.3%, 64.5%, 79.5%, and 60.2%, respectively; pooled estimates for specificity were 74.5%, 68.5%, 72.6%, and 97.4%, respectively; the diagnostic odds ratios were 7.31, 3.73, 10.42, 69.48, respectively; and the area under the summary receiver operating characteristic curves were 0.766, 0.647, 0.959, and 0.818, respectively. Performance of the screening method varied based on the reference standard used; pooled estimates using either colposcopy-directed biopsy or biopsy alone as the reference standard generally reported lower estimates; pooled estimates using either colposcopy alone or liquid-based cytology as references reported higher estimates. CONCLUSIONS AND IMPLICATIONS: This meta-analysis found primary HPV testing to be the highest performing cervical cancer screening method in accurately identifying or excluding CIN2+. Further evaluation of performance at different CIN thresholds is warranted.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

Background: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. Methods: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Results: Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). Conclusion: In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Increased incidence of symptomatic peripheral neuropathy among adults receiving stavudine- versus zidovudine-based antiretroviral regimens in Kenya.

The incidence of peripheral neuropathy (PN) among adults initiating antiretroviral therapy (ART) containing stavudine (d4T) versus zidovudine (ZDV) is not well described. We compared 1-year incidence between d4T- and ZDV-based regimens in adults initiating ART in a programmatic setting in Kenya. Of 1,848 adults on ART, 1,579 (85 %) initiated d4T-based and 269 (15 %) initiated ZDV-based regimens. One-year incidence of symptomatic PN per 100 person-years was 21.9 (n=236) among d4T users and 6.9 (n=7) among ZDV users (P=0.0002). D4T was associated with 2.7 greater risk of PN than ZDV (adjusted hazard ratio, 2.7, P=0.009). In settings with continued d4T use, such as Africa, the effects of d4T on PN compared to ZDV should be considered when choosing ART regimens.

Cardiovascular risk factors and markers of myocardial injury and inflammation in people living with HIV in Nairobi, Kenya: a pilot cross-sectional study.

OBJECTIVES: To determine the prevalence of cardiovascular disease (CVD) risk factors and explore associations with high-sensitivity cardiac troponin I (hscTnI) and high-sensitivity C-reactive protein (hsCRP) in people living with HIV (PLHIV) in Kenya. DESIGN: Pilot cross-sectional study. SETTING: Data were collected from community HIV clinics across two sites in Nairobi, Kenya, from July 2019 to May 2020. PARTICIPANTS: Convenience sample of 200 PLHIV (≥30 years with no prior history of CVD). OUTCOME MEASURES: Prevalence of cardiovascular risk factors and its association with hsTnI and hsCRP levels. RESULTS: Across 200 PLHIV (median age 46 years, IQR 38-53; 61% women), the prevalence of hypercholesterolaemia (total cholesterol >6.1 mmol/L) and hypertension were 19% (n=30/199) and 30% (n=60/200), respectively. Smoking and diabetes prevalence was 3% (n=5/200) and 4% (n=7/200). HscTnI was below the limit of quantification (<2.5 ng/L) in 65% (n=109/169). High (>3 mg/L), intermediate (1-3 mg/L) and low (<1 mg/L) hsCRP levels were found in 38% (n=75/198), 33% (n=65/198) and 29% (n=58/198), respectively. Framingham laboratory-based risk scores classified 83% of PLHIV at low risk with 12% and 5% at intermediate and high risk, respectively. Older age (adjusted OR (aOR) per year increase 1.05, 95% CI 1.01 to 1.08) and systolic blood pressure (140-159 mm Hg (aOR 2.96; 95% CI 1.09 to 7.90) and >160 mm Hg (aOR 4.68, 95% CI 1.55 to 14) compared with <140 mm Hg) were associated with hscTnI levels. No associations were observed between hsCRP and CVD risk factors. CONCLUSION: The majority of PLHIV-using traditional risk estimation systems-have a low estimated CVD risk likely reflecting a younger aged population predominantly consisting of women. Hypertension and hypercholesterolaemia were common while smoking and diabetes rates remained low. While hscTnI values were associated with increasing age and raised blood pressure, no associations between hsCRP levels and traditional cardiovascular risk factors were observed.

Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy.

OBJECTIVES: Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART). DESIGN: Prospective observational study. METHODS: Participants' pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1-9%) or high-frequency drug-resistant variants (10-100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters. RESULTS: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants. CONCLUSION: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants' frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.