HIV-uninfected People Research Articles

Higher prevalence of kidney function impairment among older people living with HIV in Uganda.

People living with HIV (PLWH) are at risk of kidney function impairment due to HIV-related inflammation, antiretroviral therapy (ART), diabetes mellitus, and hypertension. Older persons may experience a higher burden of chronic kidney disease (CKD) as kidney function declines with increasing age. There is a paucity of data comparing the prevalence of kidney function impairment in older PLWH to that in HIV-uninfected people in sub-Saharan Africa. We conducted a cross-sectional study among people aged ≥ 60 years living with and without HIV in Kampala, Uganda who were matched 1:1 by community location. We collected data on sociodemographics, comorbidities, and HIV-related clinical characteristics. We defined kidney function impairment as an estimated glomerular filtration rate(eGFR) < 60mls/min/1.73m2 with or without proteinuria. We constructed multivariable logistic regression models to study associations between participant characteristics and kidney function impairment. We enrolled 278 people (median age 66 years); 50% were PLWH, and 51.8% were female. Overall, the prevalence of kidney function impairment was 23.0% (95% CI:18.4%-28.4%); 33.1% (95% CI: 25.7%-41.4%) versus 12.9% (95% CI: 8.3%-19.7%) among people living with and without HIV (p-value < 0.01). The prevalence of proteinuria among PLWH versus people without HIV was 43.9% (95% CI:35.8%-52.3%) versus 19.4% (95% CI:13.6%-26.9%) p-value < 0.01. Living with HIV (OR = 3.89(95% CI: 2.04-7.41), p-value < 0.01), older age (OR = 1.13, (95% CI:1.07-1.20), p-value < 0.01), female sex (OR = 1.95, (95% CI:1.06-3.62), p-value = 0.03) and a prior diagnosis of hypertension (OR = 2.19(95% CI:1.02-4.67), p-value = 0.04) were significantly associated with kidney function impairment. HIV infection is strongly associated with kidney function impairment among older PLWH. Prioritizing routine measurements of kidney function and proteinuria in older PLWH will enable early detection and institution of measures to reduce the progression of kidney disease.

Evaluation of immune status and selected sirtuins in people living with HIV after fully vaccinating for COVID-19

The introduction of protective vaccination against COVID-19 was a turning point in the fight against the pandemic. Expectations also concerned the effectiveness of vaccines in inducing a strong immune response against the SARS-CoV-2 virus and the length of post-vaccination immunity. This topic seems to be especially important in the case of immunocompromised people such as those living with HIV (PLWH). The aim of the study was to examine the concentration of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus’spike protein as a marker of humoral response and the concentration of interferon-gamma (IFN-γ) as an indicator of cellular response in PLWH undergoing combination antiretroviral therapy (cART) and uninfected people (control group) several months after the COVID-19 booster. Concentrations of selected enzymes from the group of sirtuins (SIRT1,-3,-6) that participate in the course of HIV infection were also examined. Concentrations of IgG and IFN-γ were statistically significantly lower in PLWH compared to the control group. Correlations between IgG and IFN-γ concentrations were found both in PLWH and in the control group. Only the concentration of SIRT-6 was significantly lower in PLWH compared to the control group. Vaccination for COVID-19 enabled good long-term humoral and cellular immunity in both HIV positive and uninfected people. The CD4/CD8 ratio and T CD8+ T lymphocytes count played a role in the long-term immune response to booster vaccination. The introduction of optimal cART stabilized the immune status of PLWH and had a positive effect on the humoral and cellular response against infection SARS-CoV- 2.

Acceptability of the Dapivirine Vaginal Ring and Oral Truvada Among African Users in Late-Stage of Pregnancy

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people.

IL-6, D-DIMER AND HIGH-SENSITIVITY C-REACTIVE PROTEIN IN HIV INFECTION – PRELIMINARY STUDY

Combined antiretroviral therapy (cART) provides HIV-infected people life expectancy comparable with HIV-uninfected people and turns the disease into a manageable chronic condition necessitating the need for innovative inflammatory markers. Our purpose was to determine the correlation between IL-6, D-dimer and high-sensitivity C-reactive protein (hsCRP) levels among HIV-infected and the presence of chronic inflammation during general and immunological aging and drug exposure. Material and methods: Comparative prospective study was conducted at 37 HIV-positive persons from the Center for Monitoring and Treatment of HIV-positive Patients at the Clinic for Infectious Diseases, UMBAL “Dr. G. Stranski” – Pleven (target group) and 18 HIV-negative individuals from outpatient practice (control group), aged ≥18 years. Results: The median age of seropositive persons was 40 years (24÷70 years), of the control group – 51 years (29÷72 years); 78% of the target group and 61% of the controls are men. The average duration of ART is 4 years (1÷9 years). The study of specified biomarkers in the target group found increased IL-6 in 8.11% of patients (mean 3.67±1.86 pg/mL; range 1.5÷8.62; 95% CI 3.11-5.02), increased D-dimer in 8.11% (mean 0.37±0.28 µg/mL; 0.21÷1.96; 95% CI 0.3691-0.37459) and increased hsCRP in 10.81% (mean 2.10±1.99 µg/mL; 0.19÷7.0; 95% CI 1.89-2.31). In the control group IL-6 was not increased (mean 2.75±1.67 pg/mL; 1.5÷6.91), D-dimer was increased in 16.67% (mean 0.37±0.17 µg/mL; 0.09÷0.8) and increased hsCRP – in 5.56% (mean 1.76±1.75 µg/mL; 0.19÷5.66). Il-6 was significantly higher in the target group. Conclusion: The implementation of sensitive biomarkers is crucial in the general diagnostic-therapeutic approach in aging with HIV.

Immune Responses in Lung Granulomas during Mtb/HIV Co-Infection: Implications for Pathogenesis and Therapy.

HIV and TB are the cause of significant worldwide mortality and pose a grave danger to the global public health. TB is the leading cause of death in HIV-infected persons, with one in four deaths attributable to TB. While the majority of healthy individuals infected with M. tuberculosis (Mtb) are able to control the infection, co-infection with HIV increases the risk of TB infection progressing to TB disease by over 20-fold. While antiretroviral therapy (ART), the cornerstone of HIV care, decreases the incidence of TB in HIV-uninfected people, this remains 4- to 7-fold higher after ART in HIV-co-infected individuals in TB-endemic settings, regardless of the duration of therapy. Thus, the immune control of Mtb infection in Mtb/HIV-co-infected individuals is not fully restored by ART. We do not fully understand the reasons why Mtb/HIV-co-infected individuals maintain a high susceptibility to the reactivation of LTBI, despite an effective viral control by ART. A deep understanding of the molecular mechanisms that govern HIV-induced reactivation of TB is essential to develop improved treatments and vaccines for the Mtb/HIV-co-infected population. We discuss potential strategies for the mitigation of the observed chronic immune activation in combination with both anti-TB and anti-retroviral approaches.

HIV-associated lung disease.

Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People living with HIV are at increased risk of both acute and chronic lung diseases. Although the use of effective antiretroviral therapy has diminished the burden of infectious lung disease, people living with HIV experience growing morbidity and mortality from chronic lung diseases. A key risk factor for HIV-associated lung disease is cigarette smoking, which is more prevalent in people living with HIV than in uninfected people. Other risk factors include older age, history of bacterial pneumonia, Pneumocystis pneumonia, pulmonary tuberculosis and immunosuppression. Mechanistic investigations support roles for aberrant innate and adaptive immunity, local and systemic inflammation, oxidative stress, altered lung and gut microbiota, and environmental exposures such as biomass fuel burning in the development of HIV-associated lung disease. Assessment, prevention and treatment strategies are largely extrapolated from data from HIV-uninfected people. Smoking cessation is essential. Data on the long-term consequences of HIV-associated lung disease are limited. Efforts to continue quantifying the effects of HIV infection on the lung, especially in low-income and middle-income countries, are essential to advance our knowledge and optimize respiratory care in people living with HIV.

Placenta analysis of Hofbauer cell profile according to the class of antiretroviral therapy used during pregnancy in people living with HIV

IntroductionThe use of antiretroviral therapy drastically reduces vertical transmission of Human Immunodeficiency Virus. However, recent studies demonstrate associations between ART use during pregnancy and placental inflammation, particularly within protease inhibitor (PI)-based regimens. We sought to characterize placental macrophages, namely Hofbauer cells, according to the class of ART used during pregnancy. MethodsUsing immunofluorescence and immunohistochemistry, placentas from 79 pregnant people living with HIV (PPLWH) and 29 HIV-uninfected people were analyzed to quantify the numbers and frequencies of leukocytes (CD45+) and Hofbauer cells (CD68+ and/or CD163+). PPLWH were stratified into three groups based on class of ART: non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, integrase strand-transfer inhibitor (INSTI)-based, and PI-based regimens. ResultsPlacentas of PPLWH contained significantly more leukocytes and Hofbauer cells than controls. Multivariable analyses revealed that this increase in immune cells was associated with a predominantly CD163+ profile in all ART subgroups compared to the HIV-negative group. This was characterized by an increase in total CD163+ cells in the PI and INSTI subgroups, and a higher frequency of CD163+ cells and CD163+/CD68+ ratio in the NNRTI and PI subgroups. DiscussionPlacentas of PPLWH treated with any ART regimen during their entire pregnancy displayed a selection for CD163+ cells compared to the HIV-negative group, regardless of class of ART, suggesting that class of ART does not intrinsically affect selection of CD163+ and CD68+ Hofbauer cells. Further investigations into the role of Hofbauer cells in ART-associated placental inflammation are warranted to identify the mechanisms behind their potential involvement in maternal-fetal tolerance maintenance.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Prevalence of dental caries and associated risk factors among People Living with HIV/AIDS and HIV uninfected adults at an HIV clinic in Kigali, Rwanda.

Dental caries is among the most frequent oral conditions in People Living with HIV/AIDS (PLWHA). There is a lack of baseline information on dental caries prevalence and associated risk factors among PLWHA in comparison to HIV uninfected people in Rwanda. This study was conducted to determine the prevalence of dental caries and associated risk factors among PLWHA and HIV uninfected adults at an HIV clinic of Kigali Teaching Hospital (CHUK) in Kigali, Rwanda. A comparative cross-sectional study was conducted among 200 PLWHA and 200 HIV uninfected adults aged 18 years and above attending an HIV clinic of CHUK. An oral examination was performed by a calibrated examiner. Dental caries were assessed using the WHO Decayed (D), Missing (M), and Filled Teeth (F) index (DMFT). Descriptive statistics, Chi-square, t-tests, and multiple binary logistic regression were used to analyze data. Overall, a higher prevalence (50.5%) of PLWHA had experienced dental caries (DMFT>0) compared to HIV uninfected counterparts (40.5%) (p = 0.045). The prevalence of Decayed teeth (D) was also higher (23.5%) among PLWHA compared to HIV uninfected persons (13.6%) (p = 0.011). The Mean(SD) DMFT scores among PLWHA and HIV uninfected participants were 2.28 (3.68) and 1.29 (2.21) respectively (p = 0.001). After performing multiple binary logistic regression analysis, the predictors of dental caries in PLWHA were being female (OR = 2.33; 95%CI = 1.14-4.75), frequent dental visits (OR = 4.50; 95% CI = 1.46-13.86) and detectable RNA viral load (OR = 4.50; 95% CI = 1.46-13.86). In HIV uninfected participants, the middle age range (36-45 years), and frequent dental visits were significantly associated with dental caries (OR = 6.61; 95%CI = 2.14-20.37) and (OR = 3.42; 95%CI: 1.337-8.760) respectively. The prevalence of dental caries was higher in PLWHA than in HIV uninfected counterparts. The reported higher prevalence of caries in PLWHA was associated with being female, detectable viral load, and frequent dental visits. Therefore, there is a need for effective oral health interventions specific to PLWHA in Rwanda to raise awareness of the risk of dental caries and provide preventive oral health services among this population. To ensure timely oral health care amongPLWHA, there is a need for an effort from policymakers and other stakeholders to integrate oral health care services within the HIV treatment program in Rwanda.

Efficacy of COVID-19 Vaccination in People Living with HIV: A Public Health Fundamental Tool for the Protection of Patients and the Correct Management of Infection.

HIV/AIDS is considered a risk factor for increased mortality due to COVID-19. For this reason, it is essential to include this population in vaccination campaigns. Studies found that antibodies are lower in HIV+ patients than in healthy individuals. The aim of this study was to assess the immune response in a cohort of people living with HIV/AIDS (PLWH) vaccinated with COVID-19 vaccination in order to evaluate the role played by the HIV infection in the efficacy of this vaccine. We carried out a cross-sectional study in the period April-September 2021, involving a cohort of PLWH and a cohort of HIV-uninfected people as the control group. The efficacy of vaccination was high in both groups despite a slight and not significant difference between them. However, important differences were found according to the intensity of the immune response. Specifically, while in the HIV+ group almost a quarter of people had a low response, it is important to remark that the control group had only a high or intermediate response after vaccination. Our results suggest the high efficacy of the mRNA COVID-19 vaccine in PLWH and the importance to vaccinate against COVID-19 in these patients in order to increase their protection.

Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV.

BackgroundIncreased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marker for CVD in the general population.MethodsWe cross-sectionally analyzed plasma of 95 PLWH on ART and 52 controls. We measured GDF-15, fibroblast growth factor-21 (FGF-21), glucagon-like peptide-2 (GLP-2), soluble urokinase plasminogen activator receptor (suPAR), CRP, and anti-CMV and anti-EBV IgG levels. All participants had no clinical CVD and underwent coronary CT angiography with the 3D reconstruction of coronary artery atherosclerotic plaques. Total plaque volume (TPV) and low attenuation plaque volume (LAPV, defined as density <30 Hounsfield Units) were calculated (mm3).ResultsIn both PLWH and controls, GDF-15 levels were increased in participants with presence of coronary plaque vs. without (p = 0.04 and p < 0.001, respectively) and correlated with TPV (r = 0.27, p = 0.009 and r = 0.62, p < 0.001, respectively) and LAPV (r = 0.28, p = 0.008, r = 0.60, p < 0.001, respectively). However, in a multivariate model, GDF-15 was independently associated with LAPV in controls only (adjusted OR 35.1, p = 0.04) and not in PLWH, mainly due to confounding by smoking. Other markers were not independently associated with plaque volume, except for anti-EBV IgGs in controls (adjusted OR 3.51, p = 0.02).ConclusionIn PLWH, GDF-15 and smoking seemed to synergistically contribute to coronary plaque volume. Conversely, increased GDF-15 levels were associated with the presence of coronary artery plaques in people without HIV, independently of CV risk factors.

SARS-CoV-2 Infection and Vaccination Coverage among Fragile Populations in a Local Health Area of Northern Italy.

Italy was dramatically hit by the COVID-19 pandemic, and the province of Brescia was one of the epicenters of the outbreak. Furthermore, Brescia has one of the highest incidences of people living with HIV (PLWH) and a substantial presence of migrants. We conducted a retrospective cohort study involving all citizens connected to the Brescia Health Protection Agency, assessing the SARS-CoV-2 burden, COVID-19 prevalence, and vaccination coverage. A total of 1,004,210 persons were included, 3817 PLWH and 134,492 foreigners. SARS-CoV-2 infection, hospitalizations and death were more frequent among Italians than foreigners. SARS-CoV-2 infections and deaths were more frequent in HIV-uninfected people than in PLWH. PLWH and foreigners were less likely to have a SARS-CoV-2 diagnosis compared to HIV-negative patients. Migrants were more likely to be hospitalized but had a lower risk of death compared to HIV-negative patients. Regarding vaccination, 89.1% of the population received at least one dose of vaccine, while 70.4% of the Italian citizens and 36.3% of the foreigner subjects received three doses of vaccine. Foreigners showed a lower risk of being diagnosed with SARS-CoV-2 but a higher risk of complications. HIV infection was not associated with a higher risk of SARS-CoV-2 severe manifestations compared to the general population. COVID-19 vaccine hesitancy was not different between PLWH and HIV uninfected people, but foreigners were more hesitant.

EPIDEMIOLOGICAL STUDY INVESTIGATING THE INCIDENCE RATE OF CVD AT VARIOUS HIV STAGES

Objective: To determine cardiovascular disease in different stages of HIV/AIDS and its associated risk factors in HIV-infected individuals. Methods: A prospective, observational study conducted with cardiovascular diseases at baseline. The data included information includes data on HIV infection at various stages, echocardiography, demographic values, cumulative incidence and statistical significance. Results: The relative risk of cardiovascular disease was found to be 1.61 [95% confidence interval (CI) 1.43–1.81] among people living with HIV (PLHIV) without antiretroviral therapy (ART) compared with HIV-uninfected people and the relative risk was identified as 2.00 (95% CI 1.70–2.37) among PLHIV on ART compared with HIV-uninfected people. There was a positive correlation between low CD4 count and echocardiographic abnormalities. Other occurrences such as cardiomyopathy, pericardial effusion, and pulmonary hypertension were also noted. Conclusion: In conclusion, it is clear that cardiovascular complications are highly seen in HIV-infected patients and these complications are increasing with the increase of the stages of HIV. PLHIV exhibit multiple known risk factors for cardiovascular disease.

Antiretroviral Drug Transporters and Metabolic Enzymes in Circulating Monocytes and Monocyte-Derived Macrophages of ART-Treated People Living With HIV and HIV-Uninfected Individuals.

Membrane-associated drug transport proteins and drug metabolic enzymes could regulate intracellular antiretroviral (ARV) drug concentrations in HIV-1 target cells such as myeloid cells. We investigated the expression of these transporters and enzymes in monocyte subsets and monocyte-derived macrophages (MDMs) isolated from peripheral blood mononuclear cells (PBMCs) of HIV-uninfected individuals (HIV-negative) and people living with HIV receiving viral suppressive antiretroviral therapy (ART; HIV+ART) and examined plasma and intracellular ARV concentrations. Monocytes were isolated from PBMCs of 12 HIV-negative and 12 HIV+ART donors and differentiated into MDMs. The mRNA and protein expression of drug transporters and metabolic enzymes were analyzed by quantitative real-time polymerase chain reaction and flow cytometry, respectively. ARV drug concentrations were quantified in plasma, PBMCs, monocytes, and MDMs by LC-MS/MS. The mRNA expression of relevant ARV transporters or metabolic enzymes, ABCB1/P-gp, ABCG2/BCRP, ABCC1/MRP1, ABCC4/MRP4, SLC22A1/OCT1, SLC29A2/ENT2, CYP2B6, CYP2D6, and UGT1A1, was demonstrated in monocytes and MDMs of 2 to 4 HIV-negative donors. P-gp, BCRP, and MRP1 proteins were differentially expressed in classical, intermediate, and nonclassical monocytes and MDMs of both HIV+ART and HIV-negative donors. Intracellular concentrations of ARVs known to be substrates of these transporters and metabolic enzymes were detected in monocytes of HIV+ART donors but were undetectable in MDMs. In this study, we demonstrated the expression of drug transporters and metabolic enzymes in monocytes and MDMs of HIV-negative and HIV+ART individuals, which could potentially limit intracellular concentrations of ARVs and contribute to residual HIV replication. Further work is needed to assess the role of these transporters in the penetration of ARVs in tissue macrophages.

Insight of PrEP and Testing STI Puzzle

Pre Exposure Prophylaxis (PrEP) is the use of Anti Retroviral (ARV) drugs by HIV-uninfected people to block the acquisition of HIV before exposure to HIV. There are concerns that PrEP introduction and scale up may pose risks, such as sexual behavior change in specific populations, and have an impact on the budget in already constrained health systems. Therefore, public health measures for the prevention of HIV and other STIs need to be enhanced, such as the prioritization of PrEP, coupled with more effective STI screening and treatment. Integration of STI and PrEP programmes can be viewed bi-directionally (not only integrating STI services into PrEP services but also considering STI clients as people also at risk for HIV and therefore potentially eligible for PrEP). This approach fosters synergies and efficiencies from a public health perspective. However, there are many challenges to programmatic integration, including siloed funding streams and programmes, the availability and costs of expanded etiological STI testing, and gaps in capacity and training for STI management. Keywords : PrEP, STI, services

Human immunodeficiency virus, diabetes mellitus and thyroid abnormalities: Should we be screening?

BackgroundDiabetes mellitus (DM) and human immunodeficiency virus (HIV) are associated with thyroid abnormalities. Scarce literature exists on the prevalence of thyroid abnormalities in people living with HIV (PLWH) and DM (PLWHD). Guidelines vary regarding thyroid-stimulating hormone (TSH) screening in PLWH and/or DM.ObjectivesThis study describes thyroid abnormalities in PLWHD and HIV-uninfected people living with DM (PLWD).MethodThis was a cross-sectional analysis of demographic, clinical and biochemical data including TSH results of first-visit patients to the Edendale Hospital diabetes clinic between January 2016 and December 2017.ResultsA total of 915 patients were enrolled: 165 PLWHD and 750 PLWD. Overall prevalence of thyroid disorders in PLWD was 8.53% (64/750). The occurrence of ‘total’ thyroid disorders and of ‘subclinical-hypothyroidism’ (SCH) was higher in PLWHD than PLWD (23.03% vs. 8.53% and 20.61% vs. 4%, p < 0.001; respectively). People living with HIV and diabetes with thyroid disorders had lower CD4 counts than PLWHD without thyroid disorders (376.08 ± 333.30 vs. 509 ± 341.7 cells/mm3; p = 0.004). Subclinical-hypothyroidism was more common in patients on antiretroviral therapy [ART] (27/136 [19.85%] vs. 4/27 [14.81%], p < 0.001). A significant number of PLWHD acquired HIV before the onset of DM (107/165 [64.85%] vs. 58/165 [35.15%], p < 0.001). Patients on ART were more likely to develop DM, OR 2.66 (95% CI 1.11–6.38).ConclusionOur study showed an increased prevalence of thyroid disorders (especially SCH) in PLWD and a higher prevalence in PLWHD. Young, overweight, female PLWHD were at risk of SCH. People living with HIV and DM on ART demonstrated an increased prevalence of thyroid dysfunction and poor lipaemic control. The introduction of combined communicable–non-communicable disease clinics might provide an integrated patient screening option.

HIV serostatus, inflammatory biomarkers and the frailty phenotype among older people in rural KwaZulu-Natal, South Africa

Objective: We compared the prevalence of frailty by HIV serostatus and related biomarkers to the modified frailty phenotype among older individuals in a rural population in South Africa. Methods: Questionnaire data were from a cohort of people living with HIV (PWH) on antiretroviral therapy (ART) and HIV-uninfected people aged 50 years and older sampled from the Africa Health Research Institute Demographic Health and Surveillance area in northern KwaZulu-Natal. The prevalence of frailty was compared using five categories: (1) physical activity; (2) mobility; (3) fatigue; (4) gait speed; and (5) grip strength, and assessed for demographic, clinical, and inflammatory correlates of frailty. Results: Among 614 individuals in the study, 384 (62.5%) were women. The median age at study enrolment was 64 years [Interquartile range (IQR) (58.6–72.0)]. 292 (47.6%) were PWH. 499 (81%) were classified as either pre-frail or frail. 43 (7%) were frail and HIV positive, 185 (30%) were pre-frail and HIV positive, 57 were frail and HIV negative and 214 (35%) were pre-frail and HIV negative. Frailty was similar for HIV negative and PWH (17.7% vs 14.7%, p = 0.72). Women were more likely to be frail (18.3% vs 13.04%, p = 0.16). The prevalence of frailty increased with age for both HIV groups. In the multivariable analysis, the odds of being frail were higher in those aged 70 years and above than those aged between 50 and 59 years (p < 0.001). Females were less likely to be pre-frail than males (p < 0.001). There was no association between any of the inflammatory biomarkers and frailty and pre-frailty. Conclusion: In this population, the prevalence of frailty is similar for PWH and people without HIV, but higher for women than men. These data suggest that the odds of developing frailty is similar for PWH over the age of 50 years, who survive into older age, as for people without HIV.

Long-term Persistence of Oral HPV Over 7 Years of Follow-up.

BackgroundHuman papillomavirus–related oropharyngeal cancer (HPV-OPC) incidence is increasing, but the natural history of the precursor—oral HPV—has not been well described.MethodsThis observational cohort study of people living with HIV and at-risk HIV uninfected people evaluated participants semiannually using 30-second oral rinse and gargle specimens over 7 years. Initially, 447 participants were followed for 4 years as part of the Persistent Oral Papillomavirus Study, and a subset of 128 who showed persistent infections at the last Persistent Oral Papillomavirus Study visit had an additional visit, as part of the Men and Women Understanding Throat HPV Study, on average 2.5 years later. Extracted DNA from oral rinse and gargle specimens was amplified using polymerase chain reaction and type specification of 13 oncogenic HPV types. Risk factors for oncogenic oral HPV clearance were evaluated using Cox models.ResultsThe majority of oncogenic oral HPV infections cleared quickly, with a median time to clearance of 1.4 years (interquartile range = 0.5-3.9 years). After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV-16 viral load was statistically significantly associated with clearance (per 10-fold decrease in copy number: adjusted hazard ratio [aHR] = 2.51, 95% confidence interval [CI] = 1.20 to 5.26; P = .01). Adjusted analyses showed that oncogenic oral HPV clearance was lower among prevalent than incident-detected infections (aHR = 0.44, 95% CI = 0.35 to 0.55), among men than women (aHR = 0.74, 95% CI = 0.60 to 0.91), for older participants (aHR per 10 years increasing age = 0.81, 95% CI = 0.74 to 0.89), and among people living with HIV (aHR = 0.76, 95% CI = 0.60 to 0.95). One participant who had oral HPV-16 consistently detected at 10 study visits over 4.5 years was subsequently diagnosed with HPV-OPC.ConclusionsThis prospective study of oncogenic oral HPV infection is the longest and largest quantification of oral HPV-16 infections to date.

Molecular imaging of cardiovascular inflammation and infection in people living with HIV infection

Widespread use of effective antiretroviral therapy (ART) in people living with human immunodeficiency virus (PLHIV) infection has changed the prognosis of the disease from a fatal and debilitating one to a chronic manageable illness. ART leads to immune restoration, but immune functional levels seen in HIV-uninfected people are never achieved. The dynamics of immune suppression, chronic immune activation, and immune senescence predispose PLHIV to certain inflammatory and infectious conditions of the cardiovascular system. Atherosclerotic cardiovascular disease is a chronic inflammatory condition that is a rising cause of mortality and morbidity among PLHIV. Certain risk factors prevalent among PLHIV, such as intravenous drug abuse, use of ART, and susceptibility, to tuberculous disease even at near-normal immune functional levels predispose them to inflammation and infections of the different components of the heart including the pericardium, epicardium, and endocardium. Molecular imaging using radionuclide techniques has been shown to have excellent clinical utility in the evaluation of inflammation and infection. The strengths of molecular imaging techniques lie in their sensitivity for early disease detection before morphological changes occur and in therapy response assessment before significant reparative changes have occurred. Molecular imaging techniques are now becoming more widespread in clinical application with increasing availability and utilization in developing countries where the most significant burden of HIV infection is felt. This review aimed to present an update on the evidence supporting the role of molecular imaging modalities with radionuclide techniques for imaging of cardiovascular inflammation and infection focusing on atherosclerotic cardiovascular disease, pericarditis, myocarditis, and endocarditis in PLHIV.

Novel Insights in the Management of Dyslipidemia in Patients With HIV Infection

In recent years, cardiovascular diseases (CVD) have become a leading cause of death in patient with HIV infection, despite a reduction of total mortality in this population. Patients with HIV who are receiving antiretroviral therapy (ART) have approximately 1.5–2 times higher risk for cardiovascular events than HIV-uninfected people. Dyslipidemia is a major risk factor for CVD and is more prevalent in patients with HIV infection. In the present review, we summarize the current concepts in the management of dyslipidemia in patients with HIV infection. Several studies evaluated the safety and effectiveness of statins in the management of dyslipidemia in patients with HIV infections. However, most studies are small and short term and none evaluated the effects of statins on cardiovascular morbidity. There are also very limited data on the role of other lipid-lowering agents in these patients. Moreover, the effect of switching ART on the lipid profile and on viral suppression is also unclear. Management of dyslipidemia in patients with HIV infection is complicated by the increased risk for pharmacokinetic interactions between lipid-lowering agents and ART as well as by the adverse metabolic effects of most classes of ART. However, given the increased cardiovascular risk of this population, lipid-lowering treatment, primarily with statins, should be considered and appears to be equally effective as in non-HIV infected subjects.