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Background: In 2007–2012 the Mexican government launched the National HIV program and there was a major change in HIV policies implemented in 2013–2018, when efforts focused on prevention, increase in early diagnosis and timely treatment. Still, late HIV diagnosis is a major concern in Mexico due to its association with the development of AIDS development and mortality. Thus, the objectives of this study were to identify the determinants of late HIV diagnosis (i.e. CD4 count less than 200 cells/mm3) in Mexico from 2008 to 2017 and to evaluate the impact of the 2013–2017 National HIV program. Methods: Using patient level data from the SALVAR database, which includes 64% of the population receiving HIV care in Mexico, an adjusted logistic model was conducted. Main study outcomes were HIV late diagnosis which was defined as CD4 count less than 200 cells/mm3 at diagnosis. Results: The study included 106,830 individuals newly diagnosed with HIV and treated in Mexican public health facilities between 2008 and 2017 (mean age: 33 years old, 80% male). HIV late diagnosis decreased from 45 to 43% (P < 0.001) between 2008 and 2012 and 2013–2017 (i.e. before and after the implementation of the 2013–2017 policy). Multivariable logistic regressions indicated that being diagnosed between 2013 and 2017 (odds ratio [OR] = 0.96 [95% Confidence interval [CI] [0.93, 0.98]) or in health facilities specialized in HIV care (OR = 0.64 [95% CI 0.60, 0.69]) was associated with early diagnosis. Being male, older than 29 years old, diagnosed in Central East, the South region of Mexico or in high-marginalized locality increased the odds of a late diagnosis. Conclusions: The results of this study indicate that the 2013–2017 National HIV program in Mexico has been marginally successful in decreasing the proportion of individuals with late HIV diagnosis in Mexico. We identified several predictors of late diagnosis which could help establishing health policies. The main determinants for late diagnosis were being male, older than 29 years old, and being diagnosed in a Hospital or National Institute. [ABSTRACT FROM AUTHOR]

The article discusses reduction in serious AIDS-related or non-AIDS-related illnesses in early HIV infection by immediate antiretroviral therapy (ART) as compared to deferred ART. Topics discussed include establishing criteria for treatment based delivering HIV care, endorsing treatment regardless of CD4+ count by HIV guidelines and prevention of tuberculosis (TB) by Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis against Tuberculosis in HIV-infected Adults (TEMPRANO) trials.

Background It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. Methods We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P <.05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. Results We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry–funded trials were more likely to be double-blinded (28.1% vs 10.3%; P =.03) and to describe missing data handling (78.5% vs 59.0%; P =.02). The overall risk of bias was low in 96 of 160 studies (60.0%). Conclusions ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence. [ABSTRACT FROM AUTHOR]

Questions: In adults with HIV-1 infection, does immediate antiretroviral therapy (ART) reduce severe illness compared with deferred ART? Does isoniazid preventive therapy (IPT) reduce severe illness compared with no IPT? Methods Design: Randomized, controlled, 2 x 2 factorial trial (TEMPRANO ANRS 12136 trial). ClinicalTrials.gov NCT00495651. Allocation: Concealed.* Blinding: Unblinded.* Follow-up period: 30 months. Setting: 9 centers in Abidjan, Ivory Coast. Patients: 2076 patients ≥ 18 years of age (median age 35 y, 79% women, median CD4+ count 459 to 467 cells/mm[sup 3]) who had HIV-1 infection or dual HIV-1 and HIV-2 infection, CD4+ count < 800 cells/mm[sup 3], and did not meet World Health Organization (WHO) criteria for starting ART. Intervention: ART started immediately (n = 1041) or deferred until WHO criteria for starting ART were reached (n = 1035). Patients were also randomized to IPT, 300 mg/d starting 1 month after randomization and continuing for 6 months (n = 1038), or no IPT (n = 1038). Outcomes: Primary outcome was a composite of all-cause mortality or severe HIV-related illness (AIDS-defining disease, non–AIDS-defining cancer, or non–AIDS-defining invasive bacterial disease). Other outcomes included grade 3 or 4 adverse events (severe or life-threatening events including gastrointestinal, respiratory, cardiovascular, cutaneous, neurologic, or other adverse events, or hematologic or biochemical test abnormalities). Patient follow-up: 85% completed the 30-month visit or died (intention-to-treat analysis). Main results: Immediate ART, with or without IPT, reduced the primary outcome compared with deferred ART, with or without IPT (Table). IPT, with early or deferred ART, reduced the primary outcome compared with no IPT, with early or deferred ART (Table). No interaction was found between treatments and the primary outcome. Immediate ART did not differ from deferred ART and IPT did not differ from no IPT for all-cause mortality (Table). Immediate ART increased grade 3 or 4 adverse events at < 6 months (4.2% vs 1.7%, relative risk increase 154%, 95% CI 46 to 338) and reduced events at 6 to 30 months (2.6% vs 5.6%, relative risk reduction 52%, CI 23 to 69) compared with deferred ART; IPT did not differ from no IPT for grade 3 or 4 adverse events at < 6 months or 6 to 30 months. Conclusion: In adults with HIV-1 infection, immediate vs deferred antiretroviral therapy and isoniazid preventive therapy vs no isoniazid reduced severe illness at 30 months. [ABSTRACT FROM AUTHOR]

Question: In adults with HIV infection and CD4+ count > 500 cells/mm[sup 3], does immediate antiretroviral therapy (ART) reduce serious AIDS-related or non–AIDS-related illnesses compared with deferred ART? Methods Design: Randomized controlled trial (Strategic Timing of Antiretroviral Therapy [START] study). ClinicalTrials.gov NCT00867048. Allocation: Concealed.* Blinding: Blinded* (outcome adjudicators). Follow-up period: Mean 3 years. Setting: 215 centers in 35 countries. Patients: 4685 generally healthy patients ≥ 18 years of age (median age 36 y, 73% men, median CD4+ count 651 cells/mm[sup 3]) who were HIV positive, had 2 CD4+ counts > 500 cells/mm[sup 3]≥ 2 weeks apart ≤ 60 days before enrollment, and had not started ART. Exclusion criteria included pregnancy, breastfeeding, or history of AIDS. Intervention: ART started immediately (n = 2326) or deferred until CD4+ count reached ≤ 350 cells/mm[sup 3] or an AIDS-related event or other condition requiring ART occurred (n = 2359). Outcomes: Primary outcome was a composite of serious AIDS-related events (death due to AIDS or any AIDS-defining event other than nonfatal herpes simples virus infection or esophageal candidiasis) or serious non–AIDS-related events (death not related to AIDS, cardiovascular disease, end-stage renal disease, decompensated liver disease, or non–AIDS-defining cancer other than basal cell or squamous cell skin cancer). Other outcomes included components of the composite outcome, all-cause mortality, grade 4 events (symptomatic, non–AIDS-related, potentially life-threatening events requiring medical intervention), and unscheduled non–AIDS-related hospitalization. Patient follow-up: 95% (intention-to-treat analysis). Main results: Immediate ART reduced serious AIDS-related and non–AIDS-related events compared with deferred ART; groups did not differ for all-cause mortality, grade 4 events, or unscheduled non–AIDS-related hospitalizations (Table). Conclusion: In adults with HIV infection and CD4+ count > 500 cells/mm[sup 3], immediate antiretroviral therapy reduced serious illnesses compared with deferred therapy. [ABSTRACT FROM AUTHOR]

Objective: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle‐aged and older Canadians living with HIV. Design: Cross‐sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort. Methods: The frailty indicator phenotype was adapted from Fried's criteria using self‐report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty. Results: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29–5.03] and arthritis (OR = 2.54, 95% CI: 1.58–4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05–3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty. Conclusions: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV‐related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV. [ABSTRACT FROM AUTHOR]

The article offers information on novel approaches for the development and delivery of tuberculosis (TB) vaccines with a thorough understanding of pathogenicity of Mycobacterium (M) and immunology. Topics covered include the M bovis-based Bacille Calmette-Guérin (BCG) vaccine for infants and the M tuberculosis immunodominant antigen with activator adjutant T helper cell type 1 (Th1). Also discussed are antigen-preventing cells (APCs) and respiratory mucosal (RM) or intradermal vaccination.

Purpose: The purpose of this study is to estimate the extent to which people aging with HIV meet criteria for successful aging as operationalized through HRQL and maintain this status over time. A second objective is to identify factors that place people at promise for continued successful aging, including environmental and resilience factors. Methods: Participants were members of the Positive Brain Health Now (BHN) cohort. People ≥ 50 years (n = 513) were classified as aging successfully if they were at or above norms on 7 or 8 of 8 health-related quality of life domains from the RAND-36. Group-based trajectory analysis, regression tree analysis, a form of machine learning, and logistic regression were applied to identify factors predicting successful aging. Results: 73 (14·2%) met criteria for successful aging at entry and did not change status over time. The most influential factor was loneliness which split the sample into two groups with the prevalence of successful aging 28·4% in the "almost never" lonely compared to 4·6% in the "sometimes/often" lonely group. Other influential factors were feeling safe, social network, motivation, stigma, and socioeconomic status. These factors identified 17 sub-groups with at least 30 members with the proportions classified as aging successfully ranging from 0 to 79·4%. The nine variables important to classifying successful aging had a predictive accuracy of 0.862. Self-reported cognition but not cognitive test performance improved this accuracy to 0.895. The two groups defined by successful aging status did not differ on age, sex or viral load, nadir and current. Conclusion: The results indicate the important role of social determinants of health in successful aging among people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Knowledge of HIV drug resistance informs the choice of regimens and ensures that the most efficacious options are selected. In January 2014, a policy change to routine resistance testing was implemented in Ontario, Canada. The objective of this study was to investigate the policy change impact of routine resistance testing in people with HIV in Ontario, Canada since January 2014. Methods: We used data on people with HIV living in Ontario from administrative databases of the Institute for Clinical Evaluative Sciences (ICES) and Public Health Ontario (PHO), and ran ordinary least squares (OLS) models of interrupted time series to measure the levels and trends of 2-year mortality, 2-year hospitalizations and 2-year emergency department visits before (2005–2013) and after the policy change (2014–2017). Outcomes were collected in biannual periods, generating 18 periods before the intervention and 8 periods after. We included a control series of people who did not receive a resistance test within 3 months of HIV diagnosis. Results: Data included 12,996 people with HIV, of which 8881 (68.3%) were diagnosed between 2005 and 2013, and 4115 (31.7%) were diagnosed between 2014 and 2017. Policy change to routine resistance testing within 3 months of HIV diagnosis led to a decreasing trend in 2-year mortality of 0.8% every six months compared to the control group. No significant differences in hospitalizations or emergency department visits were noted. Interpretation: The policy of routine resistance testing within three months of diagnosis is beneficial at the population level. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To determine prevalence and quality of life impact of lower urinary tract symptoms (LUTS) in women living with HIV (WLWH). Methods: Cross-sectional urinary questionnaires were included in a multicenter national prospective study of the HPV vaccine in WLWH. Demographic and clinical information was abstracted from the parent study. The Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7) were administered. Wilcoxon rank sum, two-sample chi-square or Fisher's exact tests were used as appropriate to compare women with UDI-6 score ≥ 25 to those with lower UDI-6 scores on demographic and HIV-related factors. Significant categorical variables were followed up with logistic regression to estimate odds ratios (OR). Results: One hundred seventy-seven women completed urinary questionnaires (85.5% of cohort). Median age was 44.1 (37.2–50.6). Mean CD4 count was 621 (410–785), and 132 women (74.6%) were virologically suppressed. Median UDI-6 score was 4.2 (0–25). Fifty-one women (28.8%) had a UIQ-7 score > 0. Among those with a UDI-6 score of at least 25, median UIQ-7 was 9.5 (0–47.6). UDI-6 ≥ 25 was significantly associated with increasing age, higher BMI, Canada as country of origin, peri-/postmenopausal status (OR 3.37, 95% CI = 1.71 to 6.75) and being parous (OR 2.92, 95% CI = 1.27 to 7.59) (all p < 0.05). HIV-related factors were not associated with UDI-6 ≥ 25. Conclusions: LUTS were common, but we did not demonstrate a negative impact on quality of life in this sample of WLWH. Large comparative studies are needed to determine whether HIV is a risk factor for bothersome LUTS in women. [ABSTRACT FROM AUTHOR]

Background: People aging with HIV are at risk for loneliness, with stigmatization and economic marginalization added to the health challenges arising from chronic infection. This study provides evidence for the extent, contributors, and consequences of loneliness in people living with HIV, focusing on brain health and quality of life. Setting: Cross-sectional data from 856 middle-aged and older adults living with HIV recruited from 5 urban specialty clinics in Canada were drawn from the inaugural visit of the Positive Brain Health Now cohort study. Methods: Participants completed an extensive assessment of biopsychosocial variables. The prevalence, severity, and quality of life impact of self-reported loneliness were described. Clinical and environmental factors hypothesized as contributing to loneliness, and the consequences of loneliness on health and function were identified using logistic, ordinal, and linear regression. Results: Eighteen percent reported being "quite often" and 46% "sometimes" lonely. Those with more loneliness were younger, less mobile, suffered more financial hardship, and were more likely to use opioids. HIV symptoms, pain, fatigue, low motivation, stigma, and unemployment were related to loneliness. Loneliness increased the odds of cognitive impairment, low mood, stress, and poor physical health. Those who were "quite often" lonely were over 4 times more likely to report poor or very poor quality of life than those who were "almost never" lonely. Conclusion: Loneliness is common in middle-aged and older people living with HIV in Canada. Many of the associated factors are modifiable, offering novel targets for improving brain health, general health, and quality of life in HIV. [ABSTRACT FROM AUTHOR]

Objective: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence.Methods: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015.Results: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%.Conclusion: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer. [ABSTRACT FROM AUTHOR]

HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH. Setting: Multicentre, longitudinal cohort across Canada. Methods: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/ 33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose. Results: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively). Conclusions: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH. [ABSTRACT FROM AUTHOR]

Objective: To estimate the extent to which HIV-related variables, cognition, and other brain health factors interrelate with other HIV-associated symptoms to influence function, health perception, and QOL in older HIV+ men in Canada.Design: Cross-sectional structural equation modelling (SEM) of data from the inaugural visit to the Positive Brain Health Now Cohort.Setting: HIV clinics at 5 Canadian sites.Subjects: 707 men, age ≥ 35 years, HIV+ for at least one year, without clinically diagnosed dementia.Main Outcome Measures: Five latent and 21 observed variables from the World Health Organization's biopsychosocial model for functioning and disability and the Wilson-Cleary Model were analysed. SEM was used to link disease factors to symptoms, impairments, function, health perception, and QOL with a focus on cognition.Results: QOL was explained directly by depression, social role, health perception, social support, and quality of the environment. Measured cognitive performance had direct effects on activity/function and indirect effects on participation, HP and QOL, acting through self-reported cognitive difficulties and meaningful activities.Conclusion: The biopsychosocial model showed good fit, with RMSEA < 0.05. This is the first time the full model has been tested in HIV. All of the domains included in the model are theoretically amenable to intervention and many have evidence-based interventions that could be harnessed to improve QOL. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV) vaccination is safe and efficacious in women without human immunodeficiency virus (HIV). Although good immunogenicity has been observed in women living with HIV (WLWH), efficacy data in this population are needed. Methods We enrolled 420 females aged ≥9 years (range, 9–65) living with HIV. Participants were to receive 3 doses of qHPV vaccine (0/2/6 months). The main endpoint was vaccine failure (ie, incident persistent qHPV infection, cervical intraepithelial neoplasia of grade 2 or higher [CIN2+], or genital warts). We compared these rates to published rates in vaccinated and unvaccinated women without HIV as well as unvaccinated WLWH. Results Among 279 eligible women, median follow-up was 2 years. In the intention-to-treat population, the incidence rate (IR) of persistent qHPV (HPV6/11/16/18) was 2.3 per 100 person-years (/100PY) (95% confidence interval [CI], 1.1–4.1), and IR of genital warts was 2.3/100PY (95% CI, 1.2–4.1). In the per-protocol efficacy population, IR of persistent qHPV was 1.0/100PY (95% CI, 0.3–2.6) and of genital warts was 1.0/100PY (95% CI, 0.3–2.5). No cases of CIN2+ occurred. Reported rates of qHPV-related infection and disease within vaccinated women without HIV, unvaccinated women without HIV, and vaccinated WLWH: 0.1 (95% CI, 0.02–0.03), 1.5 (95% CI, 1.1–2.0), and 1.2 (95% CI, 0.2–3.4) /100PY, respectively. The rate of persistent qHPV among vaccinated WLWH was lower than among unvaccinated WLWH (2.3 vs 6.0/100PY). Conclusions Vaccinated WLWH may be at higher risk for vaccine failure than vaccinated women without HIV. However, overall rates of vaccine failure were low, and rates of persistent qHPV were lower than in unvaccinated WLWH. [ABSTRACT FROM AUTHOR]

Despite some major progress made in developing tuberculosis (TB) vaccine strategies, with a dozen novel vaccines currently in the clinical pipeline, the world is still missing an effective TB vaccine. This questions whether any major breakthroughs can be achieved without making a drastic departure from the current strategy, which creates a state of ‘near-natural immunity’, imitating the natural immunity developed after Mycobacterium tuberculosis ( Mtb ) infection. Here, we argue instead that mounting evidence suggests an effective strategy ought to induce a state of all-around ‘un-natural’ immunity comprising trained innate immunity (TII), tissue-resident memory T cells (T RM ), and anti- Mtb surface antibodies in the lung. Thus, here we summarize the latest information, thinking, and development in the field of TB and vaccines. [ABSTRACT FROM AUTHOR]

Background:  Whether a candidate tuberculosis vaccine induces clinically relevant protective T-cell repertoires in humans will not be known until the completion of costly efficacy clinical trials.Methods:  We have developed an integrated immunologic approach to investigate the clinical relevance of T cells induced by a novel tuberculosis vaccine in a phase 1 trial. This approach consists of screening for likely dominant T-cell epitopes, establishing antigen-specific memory T-cell lines for identifying CD8+ and CD4+ T-cell epitopes, determining the ability of vaccine-induced T cells to inhibit mycobacterial growth in infected cells, and examining the genetic diversity of HLA recognition and the clinical relevance of identified T-cell epitopes.Results:  A single-dose immunization in BCG-primed adults with an adenovirus-based tuberculosis vaccine elicits a repertoire of memory T cells capable of recognizing multiple Ag85A epitopes. These T cells are polyfunctional and cytotoxic and can inhibit mycobacterial growth in infected target cells. Some identified T-cell epitopes are promiscuous and recognizable by the common HLA alleles. These epitopes are clinically relevant to the epitopes identified in people with latent Mycobacterium tuberculosis infection and treated patients with tuberculosis.Conclusions:  These data support further clinical development of this candidate vaccine. Our approach helps fill the gap in clinical tuberculosis vaccine development. [ABSTRACT FROM AUTHOR]

Objective To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24 months. Design Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5 mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24 months. Adverse events were recorded throughout. Results Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38 years (IQR 32–45, range 15–66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL < 40 c/ml) at baseline, with a median CD4 count of 510 cells/mm 3 (376–695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74–3.05 fold higher peak antibody response compared to those without ( p from 0.006 to <0.0001). Conclusions This study is the first to examine the qHPV vaccine in HIV-positive women out to 24 months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination. Clinical trial registration: http://www.isrctn.com/ISRCTN33674451 [ABSTRACT FROM AUTHOR]

Background: Ethnic differences have the potential to confound associations between HIV-1 subtype and immunologic progression. We compared declines in CD4 cell counts during untreated infection for the most prevalent HIV-1 subtypes, focusing on distinguishing between the effects of viral subtype and ethnicity. Methods: We combined data from 4 European and 6 Canadian cohorts, selecting adults in the stable chronic phase of untreated HIV infection. We estimated the change in square root CD4 cell count over time for subtypes and ethnicities using mixed models, adjusting for covariates selected for their potential effect on initial CD4 cell count or its decline. Results: Data from 9772 patients were analyzed, contributing 79 175 measurements of CD4 cell count and 24 157 person-years of follow-up. Overall, there were no appreciable differences in CD4 cell count decline for viral subtypes A, CRF01_AE, CRF02_AG, C and G compared with viral subtype B; whereas the decline in CD4 cell count in patients of African ancestry was considerably slower than in patients of other ethnicity. When ethnic groups were studied separately, there was evidence for slower declines in CD4 cell count in viral subtypes C, and possibly A and G, compared with viral subtype B in patients of African ancestry but not among patients of other ethnicities, suggesting an interaction between subtype and ethnicity. Interpretation: Ethnicity is a major determinant of CD4 cell count decline; viral subtype differences may have existed but were small compared with the effect of ethnicity and were most apparent in patients of African ancestry. In developing countries, slower CD4 cell count declines among individuals of African descent may translate to a longer asymptomatic phase and increase the opportunity for HIV transmission. [ABSTRACT FROM AUTHOR]