Distinct Inflammatory Phenotypes are associated with subclinical and clinical Cardiovascular disease in People living with HIV.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with HIV (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in two independent cohorts of PWH. We identified three distinct inflammatory clusters present in both cohorts that associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

TB prevalence in Zimbabwe: a national cross-sectional survey, 2014.

BACKGROUND: We conducted the first national TB prevalence survey to provide accurate estimates of bacteriologically confirmed pulmonary TB disease among adults aged ≥15 years in 2014.METHODS: A TB symptoms screen and chest X-ray (CXR) were used to identify presumptive TB cases who submitted two sputum samples for smear microscopy, liquid and solid culture. Bacteriological confirmation included acid-fast bacilli smear positivity confirmed using Xpert® MTB/RIF and/or culture. Prevalence estimates were calculated using random effects logistic regression with multiple imputations and inverse probability weighting.RESULTS: Of 43,478 eligible participants, 33,736 (78%) were screened; of these 5,820 (17%) presumptive cases were identified. There were 107 (1.9%) bacteriologically confirmed TB cases, of which 23 (21%) were smear-positive. The adjusted prevalences of smear-positive and bacteriologically confirmed TB disease were respectively 82/100,000 population (95% CI 47-118/100,000) and 344/100,000 (95% CI 268-420/100,000), with an overall all-ages, all-forms TB prevalence of 275/100,000 population (95% CI 217-334/100,000). TB prevalence was higher in males, and age groups 35-44 and ≥65 years. CXR identified 93/107 (87%) cases vs. 39/107 (36%) using the symptom screen.CONCLUSION: Zimbabwe TB disease prevalence has decreased relative to prior estimates, possibly due to increased antiretroviral therapy coverage and successful national TB control strategies. Continued investments in TB diagnostics for improved case detection are required.

The HIV Care Cascade and sub-analysis of those linked to but not retained in care: the experience from a tertiary HIV referral service in Dublin Ireland.

BACKGROUND: The HIV Care Cascade model can be used to measure how clinical services align with United Nations' (UN) HIV treatment targets. Previous models have highlighted sequential losses at each step of the Cascade with a significant proportion being not retained in care (NRIC). OBJECTIVE: We aimed to assess the feasibility of meeting the UN targets and assess factors associated with, and calculate the true proportion of those, NRIC. METHODS: All people living with HIV who were linked to our service, one of three specialist HIV care providers in Dublin Ireland, from its establishment in 1993 to 1 December 2014, were included in the cohort and were categorized as linked to care, retained in care (RIC), on antiretroviral therapy (on ART), virally suppressed (HIV RNA <40copies/ml), and NRIC. An analysis of those NRIC was performed to categorize their current status through direct/indirect contact. RESULTS: Of 1000 patients linked to care, 78.7% (n = 787) were RIC, of whom 91.5% (n = 720) were on ART, with 89.9% (n = 644) virally suppressed. Those RIC were more likely older (p = 0.006) and non-IVDU (p < 0.001). Of 213 (21.3%) NRIC, 56 (26.3%) emigrated, 27 (12.7%) transferred care, 15 (7.0%) stopped attending but were contactable, 38 (17.8%) died, and 77 (36.1%) were lost to follow-up. After revision, 10.5% of the cohort was confirmed as NRIC, with 6 of 15 defined as "stopped attending" re-linked to care following direct contact. CONCLUSIONS: Our HIV Care Cascade model demonstrates that the true numbers of patients NRIC may be significantly lower than previously estimated and once RIC, treatment goals approaching the United Nations Programme on HIV and AIDS targets are possible with 91.5% on treatment and almost 90% of those on treatment virally suppressed. That 40% reengaged following direct contact suggests benefit through regular monitoring and direct contact based on the HIV Care Cascade model.

Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions.

OBJECTIVES: Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first-line ritonavir-boosted, protease-inhibitor (PI/r)-containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir-boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r. METHODS: In a retrospective assessment of HIV-infected patients initiating ATV/r-containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation. RESULTS: A total of 202 patients [median age 33 years (interquartile range (IQR) 29-40 years); 52% female; median CD4 count 184 cells/µL (IQR 107-280 cells/µL); median HIV RNA 4.6 log10 HIV-1 RNA copies/mL (IQR 3.2-5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10-52) weeks on ART, with a median (IQR) UTrI duration of 10 (3-31) weeks. Fifty-four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3-9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3-4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re-suppressed on ATV/r reinitiation. CONCLUSIONS: In this PI-treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r-treated patients prior to ART reinitiation after UTrI.