HIV-uninfected Participants Research Articles

Pre-frailty predicts cognitive decline at 2-year follow-up in persons living with HIV.

Both HIV disease and frailty syndrome are risk factors for neurocognitive impairment. Longitudinal research among individuals of the general population suggests that frailty predicts future cognitive decline; however, there is limited evidence for these longitudinal relationships among people living with HIV (PLWH). The current study evaluated and compared rates of cognitive decline over 2 years among HIV serostatus and frailty status groups. Participants included 50 PLWH and 60 HIV-uninfected (HIV-) participants who were evaluated at baseline and 2-year follow-up visits. Baseline frailty status (non-frail, pre-frail, and frail) was determined using fried frailty phenotype criteria. Neurocognitive functioning was measured using practice-effect corrected scaled scores derived from a comprehensive neuropsychological battery covering seven cognitive domains. Repeated measures analysis was used to estimate rates of global and domain-specific cognitive change from baseline to 2-year follow-up among each of six HIV/frailty status groups. Among PLWH, the pre-frail group demonstrated consistent declines in global cognitive functioning (B = - 0.029, p = 0.034), processing speed (B = - 0.047, p = 0.031), and motor functioning (B = - 0.048, p = 0.038). Among HIV- participants, pre-frail individuals also declined in global cognitive functioning and processing speed (ps ≤ 0.05). HIV- non-frail participants also declined in the cognitive domains of learning, delayed recall, and motor functioning; however, these declines appeared to be driven by relatively higher baseline scores among this group. Notably, 38% of PLWH changed in frailty status from baseline to follow-up, and those with stable pre-frailty demonstrated higher likelihood for cognitive decline; change in depressive symptoms did not relate to change in frailty status. Current findings highlight pre-frailty as an important clinical syndrome that may be predictive of cognitive decline among PLWH. Interventions to prevent or reduce frailty among vulnerable PLWH are needed to maintain optimal cognitive health.

Demographics and health profile on precursors of non-communicable diseases in adults testing for HIV in Soweto, South Africa: a cross-sectional study

ObjectivesThis cross-sectional study investigated the burden of HIV-non-communicable disease (NCD) precursor comorbidity by age and sex. Policies stress integrated HIV-NCD screenings; however, NCD screening is poorly implemented in South African...

No Evidence of Sexual Risk Compensation Following PrEP Initiation Among Heterosexual HIV Serodiscordant Couples in Kenya and Uganda

Recent studies among men who have sex with men suggest that sexual behaviors associated with risk of sexually transmitted infections increase following initiation of pre-exposure prophylaxis (PrEP) for HIV prevention. We used longitudinal data from HIV-uninfected participants (n = 1013) enrolled in an open-label study of PrEP delivered to Ugandan and Kenyan heterosexual HIV serodiscordant couples to understand the association between PrEP initiation and HIV risk-related sexual behaviors among these couples. In the month following PrEP initiation, the mean number of monthly sex acts within couples decreased from 7.9 to 6.9 (mean difference: − 1.1; 95% CI − 1.5, − 0.7) and the proportion of couples having condomless sex decreased from 65% to 32% (percentage point change: − 33%; 95% CI − 37%, − 30%); these behaviors then remained relatively constant over 2 years. We found no evidence of sexual risk compensation following PrEP initiation within African serodiscordant couples. However, roughly a third of couples continued to engage in condomless sex during follow up, emphasizing the importance of continued PrEP use to sustain HIV protection.

Impact of Counseling Methods on HIV Retesting Uptake in At-Risk Individuals: A Randomized Controlled Study.

Systematic face-to-face pre-HIV test counseling is costly and may discourage clients to present for regular testing. In a randomized, controlled, non-inferiority trial conducted in four facilities providing free-of-charge anonymous HIV testing in Thailand, participants received either: standard counseling according to national guidelines (reference); computer-assisted counseling: interactive counseling on a tablet computer followed by an invitation to ask questions to the counselor; or on-demand counseling: invitation to ask questions to the counselor. Primary endpoint was a HIV retest within 7months after enrolment visit. Following the planned interim analysis, on-demand counseling was discontinued for futility. In the final analysis in 1036 HIV-uninfected at-risk participants, computer-assisted counseling was non-inferior to standard counseling and had similar acceptability and improvements in HIV knowledge and sexual risk behaviors; however, it significantly reduced the time spent by counselors on counseling. Implementation of pre-HIV test computer-assisted counseling may ease the burden on staff involved in HIV testing.

Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection.

Reversing or preventing T-cell exhaustion is an important treatment goal in the context of HIV disease; however, the mechanisms that regulate HIV-specific CD8 T-cell exhaustion are incompletely understood. Since mitochondrial mass (MM), mitochondrial membrane potential (MMP), and cellular reactive oxygen species (ROS) content are altered in exhausted CD8 T cells in other settings, we hypothesized that similar lesions may arise in HIV infection. We sampled cryopreserved peripheral blood mononuclear cells from HIV-uninfected (n = 10) and HIV-infected participants with varying levels and mechanisms of viral control: viremic (VL > 2000 copies/mL; n = 8) or aviremic (VL < 40 copies/mL) due to antiretroviral therapy (n = 11) or natural control (n = 9). We characterized the MM, MMP, and ROS content of bulk CD8 T cells and MHC class I tetramer+ HIV-specific CD8 T cells by flow cytometry. We observed higher MM, MMP, and ROS content across bulk effector-memory CD8 T-cell subsets in HIV-infected compared with HIV-uninfected participants. Among HIV-specific CD8 T cells, these features did not vary by the extent or mechanism of viral control but were significantly altered in cells displaying characteristics associated with exhaustion (eg, high PD-1 expression, low CD127 expression, and impaired proliferative capacity). While we did not find that control of HIV replication in vivo correlates with the CD8 T-cell MM, MMP, or ROS content, we did find that some features of CD8 T-cell exhaustion are associated with alterations in mitochondrial state. Our findings support further studies to probe the relationship between mitochondrial dynamics and CD8 T-cell functionality in HIV infection.

244 HIV Testing History, Testing Interest, and HIV Risk-Taking Behaviors Among Adult Accident and Emergency Department Patients in Belize City

Testing for HIV in emergency departments (EDs) has been advocated for in developed countries to identify those with an undiagnosed HIV infection who might not be tested elsewhere and link them to care. However, the utility of HIV testing in developing country EDs is not yet well established. Belize has the highest HIV prevalence in Central America yet its EDs do not routinely offer HIV testing. At the Karl Heusner Memorial Hospital Authority (KHMHA) Accident and Emergency Department (A&E) in Belize City, we assessed HIV testing need among the adult population based on prevalence of lack of prior HIV testing, reported risk of HIV infection, and interest in being tested in the ED. Between June and August of 2018, we recruited a random sample of KHMHA A&E patients and surveyed them using an audio computer-assisted self-interviewer. Participants were English-speaking, 18-64 years old, not critically ill or injured, not a prison inmate/under arrest, and were able to provide informed consent. HIV positivity, prior testing prevalence, and reasons for no prior HIV testing were summarized. Reported HIV risk behaviors and HIV testing interest in the A&E were compared by prior HIV testing status. Multivariable logistic regression was used to identify factors associated with lack of previous HIV testing. Of 301 KHMHA A&E patients screened for study eligibility, patient-reported HIV prevalence was 6%. Of the 264 HIV-uninfected participants, 26% never had been tested for HIV. Of the 69 not previously HIV tested, 28% reported never having been offered testing. Of the 264 HIV-uninfected participants, 6.1% reported injection drug use and 49.2% report having condomless sex in the past 10 years. Prevalence of condomless sex with casual and exchange partners was similar for those never HIV tested vs. tested previously (casual: 25% vs. 27%, p<0.87; exchange: 7.4% vs. 9.7%, p<0.81). Belief in the importance of HIV testing for all A&E patients was similar for never HIV tested vs. tested previously (90% vs. 90%; p<0.30). Participants with fewer years of formal education (primary school or less as compared to tertiary education) (aOR: 4.75 [95% CI: 1.8, 12.4]) and males (aOR: 2.81 [95% CI: 1.5, 5.3]) were less likely to have been HIV tested (Table). Absence of prior HIV testing, lack of being offered an HIV test previously, and the high prevalence of reported HIV risk behaviors indicate that that patients in this developing country could benefit from an A&E-based HIV testing program. Furthermore, the overwhelming majority of patients are supportive of being tested for HIV in the A&E.

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa

BackgroundLittle is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa.MethodsWe used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health).ResultsAmong 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05–1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89–0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79–9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86–1.48) at age 60.ConclusionsIndependent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus.Trial registrationClinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.

Evaluating the Safety and Immunogenicity of a Prime-boost Vaccine Regimen of GEO-D02 DNA and MVA/HIV62B With and Without B63521^11 gp120 and IHV01 gp120 Env Proteins in Healthy, HIV-uninfected Adult Participants

Evaluating the Safety and Immunogenicity of a Prime-boost Vaccine Regimen of GEO-D02 DNA and MVA/HIV62B With and Without B63521^11 gp120 and IHV01 gp120 Env Proteins in Healthy, HIV-uninfected Adult Participants

A11 Evaluation of phylogenetic inference methods to determine direction of HIV transmission

It has been postulated that the direction of HIV transmission between two individuals can be determined by phylogenetic analysis of HIV sequences. This approach may be problematic, since HIV sequences from newly infected individuals are often more similar to index sequences from samples collected years before transmission, compared to those from samples collected at the time of transmission. We evaluated the accuracy of phylogenetic methods for determining the direction of HIV transmission by analyzing next-generation sequencing (NGS) data from index–partner pairs enrolled in the HIV Prevention Trials Network (HPTN) 052 trial. HIV-infected index and HIV-uninfected partner participants were enrolled as serodiscordant couples; samples were analyzed from couples with index-to-partner HIV transmission that was confirmed by genetic linkage studies. NGS for HIV gp41 (HXB2 coordinates: 7691–8374) was performed using plasma samples from thirty-nine index–partner pairs (seventy-eight samples collected within 3 months of partner seroconversion). Maximum likelihood trees were generated using the entire dataset using FastTree v.2. Topological patterns of HIV from each index–partner pair were analyzed. The analysis included 9,368 consensus sequences and 521,145 total sequence reads for the seventy-eight samples analyzed. In 10 per cent (four out of thirty-nine) of couples, the phylogeny was inconsistent with the known direction of transmission. In 26 per cent (ten out of thirty-nine) of couples, the phylogeny results could not discern directionality. In 64 per cent (twenty-five out of thirty-nine) of couples, the results correctly indicated index-to-partner transmission; in two of these twenty-five cases, only one index sequence was closest to the most recent common ancestor. Phylogenetic analysis of NGS data obtained from samples collected within 3 months of transmission correctly determined the direction of transmission in 64 per cent of the cases analyzed. In 36 per cent of the cases, the phylogenetic topology did not support the known direction of infection, and in one-third of these cases the observed topology was opposite to the known direction of transmission. This demonstrates that phylogenetic topology alone may not be sufficient to accurately determine the direction of HIV transmission.

History of tuberculosis is associated with lower exhaled nitric oxide levels in HIV-infected children.

Objective:HIV disrupts host defense mechanisms and maintains chronic inflammation in the lung. Nitric oxide is a marker of lung inflammation and can be measured in the exhaled air. We investigated the relationship between exhaled nitric oxide (eNO), HIV status and airway abnormalities in perinatally HIV-infected children aged 6–19 years.Design:A cross-sectional study.Methods:HIV-infected individuals on antiretroviral therapy and HIV-uninfected children with no active tuberculosis (TB) or acute respiratory tract infection were recruited from a public hospital in Harare, Zimbabwe. Clinical history was collected and eNO testing and spirometry was performed. The association between eNO and explanatory variables (HIV, FEV1 z-score, CD4+ cell count, viral load, history of TB) was investigated using linear regression analysis adjusted for age, sex and time of eNO testing.Results:In total, 222 HIV-infected and 97 HIV-uninfected participants were included. Among HIV-infected participants, 57 (25.7%) had a history of past TB; 56 (25.2%) had airway obstruction, but no prior TB. HIV status was associated with lower eNO level [mean ratio 0.79 (95% confidence interval, 95% CI 0.65–0.97), P = 0.03]. Within the HIV-infected group, history of past TB was associated with lower eNO levels after controlling for age, sex and time of eNO testing [0.79 (95% CI 0.67–0.94), P = 0.007].Conclusion:HIV infection and history of TB were associated with lower eNO levels. eNO levels may be a marker of HIV and TB-induced alteration in pulmonary physiology; further studies focused on potential causes for lower eNO levels in HIV and TB are warranted.

HIV infection is associated with elevated biomarkers of immune activation in Ugandan adults with pneumonia.

IntroductionPneumonia is an important cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV) infection. How immune activation differs among HIV-infected and HIV-uninfected adults with pneumonia is unknown.MethodsThe Inflammation, Aging, Microbes, and Obstructive Lung Disease (I AM OLD) Cohort is a prospective cohort of adults with pneumonia in Uganda. In this cross-sectional analysis, plasma was collected at pneumonia presentation to measure the following 12 biomarkers: interleukin 6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2), high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, soluble CD27 (sCD27), interferon gamma-inducible protein 10 (IP-10), soluble CD14 (sCD14), soluble CD163 (sCD163), hyaluronan, and intestinal fatty acid binding protein. We asked whether biomarker levels differed between HIV-infected and HIV-uninfected participants, and whether higher levels of these biomarkers were associated with mortality.ResultsOne hundred seventy-three participants were enrolled. Fifty-three percent were HIV-infected. Eight plasma biomarkers—sTNFR-1, sTNFR-2, hsCRP, D-dimer, sCD27, IP-10, sCD14, and hyaluronan—were higher among participants with HIV infection, after adjustment for pneumonia severity. Higher levels of 8 biomarkers—IL-6, sTNFR-1, sTNFR-2, hsCRP, IP-10, sCD14, sCD163, and hyaluronan—were associated with increased 2-month mortality.ConclusionsAs in other clinical contexts, HIV infection is associated with a greater degree of immune activation among Ugandan adults with pneumonia. Some of these are also associated with short-term mortality. Further study is needed to explore whether these biomarkers might predict poor long-term outcomes—such as the development of obstructive lung disease—in patients with HIV who have recovered from pneumonia.

Evaluating the Safety and Immunogenicity of an HIV-1 gp41 MPER-656 Liposome Vaccine in Healthy, HIV-uninfected Adult Participants

Evaluating the Safety and Immunogenicity of an HIV-1 gp41 MPER-656 Liposome Vaccine in Healthy, HIV-uninfected Adult Participants

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants

Elevated Plasma Ceramides Are Associated With Antiretroviral Therapy Use and Progression of Carotid Artery Atherosclerosis in HIV Infection.

Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals. Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up. Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants. In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

Sharing of Injection Drug Preparation Equipment Is Associated With HIV Infection: A Cross-sectional Study.

Background:Sharing needles/syringes and sexual transmission are widely appreciated as means of HIV transmission among persons who inject drugs (PWIDs). London, Canada, is experiencing an outbreak of HIV among PWIDs, despite a large needle/syringe distribution program and low rates of needle/syringe sharing.Objective:To determine whether sharing of injection drug preparation equipment (IDPE) is associated with HIV infection.Methods:Between August 2016 and June 2017, individuals with a history of injection drug use and residence in London were recruited to complete a comprehensive questionnaire and HIV testing.Results:A total of 127 participants were recruited; 8 were excluded because of failure to complete HIV testing. The remaining 35 HIV-infected (cases) and 84 HIV-uninfected (controls) participants were assessed. Regression analysis found that sharing IDPE, without sharing needles/syringes, was strongly associated with HIV infection (adjusted odds ratio: 22.1, 95% confidence interval: 4.51 to 108.6, P < 0.001).Conclusions:Sharing of IDPE is a risk factor for HIV infection among PWIDs, even in the absence of needle/syringe sharing. Harm reduction interventions to reduce HIV transmission associated with this practice are urgently needed.

Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates

Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507-519).

Diet Quality Is Low and Differs by Sex in People with HIV

People with HIV (PWH) are at risk for developing metabolic comorbidities driven, in part, by immune activation/inflammation. Little is known about diet quality, a potential modifiable factor in PWH. This study aimed to explore diet quality in terms of conformance with US dietary guidelines by calculating Healthy Eating Index-2010 (HEI) scores among adults with and without HIV in Boston, MA, and determine associations with HEI and markers of immune activation/inflammation. One-hundred and three HIV-infected [50 women, 53 men; mean±SD age: 47±7 y; body mass index (BMI, in kg/m2): 26±5] and 38 uninfected adults (17 women, 21 men; age: 46±7 y; BMI: 28±4) were included in this cross-sectional analysis. Participants who completed a 4-d food record from which HEI could be calculated were included. HEI was compared between participants with and without HIV, within HIV-infected participants stratified by sex, and by HIV serostatus and sex. In the HIV group, predictors of HEI were determined in multivariable modeling. Univariate associations with diet quality and inflammation/immune markers were assessed. The HEI score was 51.3 in the HIV-infected participants and 57.3 in the HIV-uninfected participants (P=0.052). In the comparison by HIV serostatus and sex, HIV-infected women had significantly lower HEI (49.2) compared with HIV-infected men (55.7) (P=0.005) and HIV-uninfected men (61.8) (P=0.002). Adjusting for potential confounding factors, sex remained an independent predictor of HEI in HIV (P=0.02). In the HIV group, higher log HEI was associated with lower concentration of the immune activation marker sCD14 (P=0.009). Diet quality tended to be lower in HIV-infected individuals compared with HIV-uninfected individuals and was lower among HIV-infected women compared with HIV-infected men, and HIV-uninfected men. There may also be an association with diet quality and sCD14 in PWH. Future prospective studies are needed to confirm these findings and determine whether improving diet quality is a useful strategy to reduce metabolic abnormalities in this population. This study was registered at clinicaltrials.gov as NCT00455793.

Measles Seroprevalence and Vaccine Responses in Human Immunodeficiency Virus-infected Adolescents and Adults: A Systematic Review.

The World Health Organization (WHO) recommends an additional dose of measles-containing vaccine (MCV) for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy following immune reconstitution. We conducted a systematic review to synthesize available evidence regarding measles seroprevalence and measles vaccine immunogenicity, efficacy, and safety in HIV-infected adolescents and adults to provide the evidence base for recommendations on the need for measles vaccination. We conducted searches of 8 databases through 26 September 2017. Identified studies were screened independently by 2 reviewers. The search identified 30 studies meeting inclusion criteria. Across studies, measles seroprevalence among HIV-infected adolescents and adults was high (median, 92%; 27 studies), with no significant difference compared to HIV-uninfected participants (10 studies). In 6 studies that evaluated the immunogenicity of MCVs among seronegative HIV-infected adults, measles seropositivity at end of follow-up ranged from 0% to 56% (median, 39%). No severe adverse events were reported following measles vaccination in HIV-infected patients. Based on similar measles seroprevalence between HIV-infected and HIV-uninfected adolescents and adults, and the low response to vaccination, these studies do not support the need for an additional dose of MCV in HIV-infected adolescents and adults. These findings support WHO guidelines that measles vaccine be administered to potentially susceptible, asymptomatic HIV-infected adults, and may be considered for those with symptomatic HIV infection if not severely immunosuppressed. Measles-susceptible adolescents and adults, regardless of HIV status, may require targeted vaccination efforts to reach critical vaccination thresholds and achieve regional elimination goals.

Reduced Forced Vital Capacity Among Human Immunodeficiency Virus-Infected Middle-Aged Individuals.

Pulmonary function impairments are more common among people living with HIV (PLWH), as are contributing risk behaviors. To understand the effects of human immunodeficiency virus (HIV) infection independent of risk behaviors, pulmonary function was evaluated in lifestyle-comparable HIV-infected and -uninfected AGEhIV cohort participants. Prevalence of obstructive lung disease in 544 HIV-infected and 529 HIV-uninfected participants was determined using spirometry. Logistic regression was used to assess HIV as a determinant of obstructive lung disease. Additional explanatory models were constructed to explain observed differences. The unadjusted obstructive lung disease prevalence was similar in HIV-infected (23.0%) and -uninfected (23.4%) participants. Multivariable logistic regression analysis showed an effect modification whereby obstructive lung disease prevalence among persons with limited smoking experience was notably lower among HIV-infected compared with HIV-uninfected participants. This resulted from a lower forced vital capacity (FVC) in HIV-infected participants but similar 1-second forced expiratory volume (FEV1), especially in those with limited smoking experience. The lower FVC in HIV-infected participants could indicate HIV-related restrictive or fibrotic pulmonary changes. Factors that decrease the FVC could obscure emphysematous changes in the lungs of PLWH when using the FEV1/FVC ratio as single diagnostic measure. NCT01466582.

Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa.

Background:Low adherence can undermine the efficacy of daily oral pre-exposure prophylaxis (PrEP). Mental health conditions, particularly depression, could be associated with low PrEP adherence, especially for women.Setting:We analyzed data from 1013 Kenyan and Ugandan HIV-uninfected participants in the Partners Demonstration Project, an open-label study of PrEP delivered to HIV-uninfected members of serodiscordant couples.Methods:Participants completed quarterly visits over 2 years and were encouraged to use PrEP until their partners living with HIV had ≥6 months of antiretroviral therapy use (when viral suppression was expected). PrEP adherence was measured daily with electronic medication event monitoring system caps and dichotomized into low (<80% of expected bottle openings) and high adherence. Depression was assessed annually using the 16-item Hopkins Symptom Checklist screening tool; scores >1.75 indicate “probable depression.” The association between probable depression and PrEP adherence was assessed separately for men and women using generalized estimating equations and marginal structural models.Results:At enrollment, 39 (11.7% of 334) women and 64 (9.4% of 679) men reported symptoms indicating probable depression, and these proportions decreased during follow-up (P < 0.001 for women and men). Probable depression was significantly associated with low PrEP adherence among women (adjusted risk ratio = 1.77; 95% confidence interval: 1.14 to 2.77; P = 0.01); there was no association between depression and adherence among men (P = 0.50). Marginal structural models and sensitivity analyses confirmed these findings.Conclusions:Depression was relatively uncommon in this population and was an independent risk factor for low PrEP adherence among women. For PrEP programs targeting African women, integration of depression screening may improve PrEP effectiveness.