Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to ...antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
At present, the majority of patients who have initiated their first antiretroviral therapy have received a combination comprising a nonnucleoside and two nucleoside analogues. The use of ...nonnucleosides as first-line therapy has been favored for their more convenient dosing, with less pill numbers, and the possibility of co-formulation with nucleoside analogues. Although protease inhibitors are also considered to be a preferred standard, they have been less frequently used as first regimen of choice because of their adverse effects in the short to medium term. The introduction of darunavir and atazanavir as new protease inhibitors boosted with ritonavir has resulted in a significant change in this area. These drugs show a lower incidence of adverse effects, allow once-a-day administration, and have a high barrier to resistance that prevents the selection of resistance mutations in case of virologic failure. On this basis, it is likely that over the next few years these drugs will become a standard of care, gaining acceptance and being used more frequently as preferred first-line regimen.
Abstract
Background
To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged ...45–60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS).
Methods
Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression.
Results
Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45–50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38–6.55 and 2.63; 1.44–4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13–4.14) and urogenital symptoms (2.54; 1.42–4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74–13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups.
Conclusions
Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.
Abstract
Thanks to advances in the field over the years, HIV/AIDS has now become a manageable chronic condition. Nevertheless, a new set of HIV-associated complications has emerged, related in part ...to the accelerated ageing observed in people living with HIV/AIDS, the cumulative toxicities from exposure to antiretroviral drugs over decades and emerging comorbidities. As a result, HIV/AIDS can still have a negative impact on patients’ quality of life (QoL). In this scenario, it is reasonable to believe that the concept of therapeutic success, traditionally associated with CD4 cell count restoration and HIV RNA plasma viral load suppression and the absence of drug resistances, needs to be redefined to include other factors that reach beyond antiretroviral efficacy. With this in mind, a group of experts initiated and coordinated the RET Project, and this group, using the available evidence and their clinical experience in the field, has proposed new criteria to redefine treatment success in HIV, arranged into five main concepts: rapid initiation, efficacy, simplicity, safety, and QoL. An extensive review of the literature was performed for each category, and results were discussed by a total of 32 clinicians with experience in HIV/AIDS (4 coordinators + 28 additional experts). This article summarizes the conclusions of these experts and presents the most updated overview on the five topics, along with a discussion of the experts’ main concerns, conclusions and/or recommendations on the most controversial issues.
Objectives
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV‐infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir ...(ATV) inhibits UDP‐glucuronosyl‐transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)‐ vs. efavirenz (EFV)‐based first‐line antiretroviral therapy (ART).
Methods
A multicentre, prospective cohort study of HIV‐infected patients who started first‐line ART with either ATV/r or EFV was conducted. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2), myeloperoxidase (MPO) and oxidized low‐density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders.
Results
After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp‐PLA2 estimated difference −16.3; 95% confidence interval (CI) −31.4, −1.25; P = 0.03 and a significantly smaller increase in OxLDL (estimated difference −21.8; 95% CI −38.0, −5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI −14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated.
Conclusions
When compared with EFV, ATV/r‐based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4
recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential ...impact in patients with very low CD4
T-cells count. We aimed to analyze the association between
rs6897932 polymorphism and CD4
T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4
T-cells count <200 cells/mm
. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4
T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy-Weinberg equilibrium (
= 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4
T-cells recovery (arithmetic mean ratio; AMR = 1.16;
= 0.016), higher CD4
T-cells increase (AMR = 1.19;
= 0.004), and higher CD4
T-cells count at the end of follow-up (AMR = 1.13;
= 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4
T-cells at the end of follow-up ≥500 CD4
cells/mm
(OR = 2.44;
= 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of ≥ 400 CD4
cells/mm
lost statistical significance (
= 0.052).
rs6897932 CT/TT genotype was related to a better CD4
T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4
T-cells count <200 cells/mm
.
The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR ...repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain β (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval CI, 17%–33%) than in the controls (7.2%, 95% CI, 2.3%–12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.
A modified vaccinia Ankara-based HIV-1 vaccine clade B (MVA-B) has been tested for safety and immunogenicity in low-risk human immunodeficiency virus (HIV)-uninfected individuals and as a therapeutic ...vaccine in HIV-1-infected individuals on combined antiretroviral therapy (cART). As a therapeutic vaccine, MVA-B was safe and broadly immunogenic; however, patients still showed a viral rebound upon treatment interruption. Monocytes are an important part of the viral reservoir and several studies suggest that they are partly responsible for the chronic inflammation observed in cART-treated HIV-infected people. The CD300 family of receptors has an important role in several diseases, including viral infections. Monocytes express CD300a, c, e, and f molecules and lipopolysaccharide (LPS) and other stimuli regulate their expression. However, the expression and function of CD300 receptors on monocytes in HIV infection is still unknown. In this work, we investigated for the first time the expression of CD300 molecules and the cytokine production in response to LPS on monocytes from HIV-1-infected patients before and after vaccination with MVA-B. Our results showed that CD300 receptors expression on monocytes from HIV-1-infected patients correlates with markers of HIV infection progression and immune inflammation. Specifically, we observed a positive correlation between the expression of CD300e and CD300f receptors on monocytes with the number of CD4+ T cells of HIV-1-infected patients before vaccination. We also saw a positive correlation between the expression of the inhibitory receptor CD300f and the expression of CD163 on monocytes from HIV-1-infected individuals before and after vaccination. In addition, monocytes exhibited a higher cytokine production in response to LPS after vaccination, almost at the same levels of monocytes from healthy donors. Furthermore, we also described a correlation in the expression of CD300e and CD300f receptors with TNF-α production in response to LPS, only in monocytes of HIV-1-infected patients before vaccination. Altogether, our results describe the impact of HIV-1 and of the MVA-B vaccine in cytokine production and monocytes phenotype.
Since SAR-COV-2 infection emerged and spread worldwide, little is known about its impact on people living with human immunodeficiency virus (HIV). We performed a single-center retrospective study to ...describe the potential particularities and risk factors for respiratory failure (RF) in that population. This single-center retrospective study included patients infected with HIV, whose current follow-up is run in this center, above18 years of age, with diagnosis of SARS-CoV-2 infection between March 5, 2020 and April 15, 2021. We collected data regarding HIV immunological and virological status, main epidemiological characteristics, as well as those conditions considered to potentially influence in SARS-CoV-2 evolution; and clinical, microbiological, radiological, respiratory status, and survival concerning coronavirus disease 2019 (COVID-19). We compared all that, for patients with and without RF and performed a logistic regression for suspected risk factors for RF. One hundred seventy-seven HIV patients were diagnosed from COVID-19 (mean age 53.8 years, 81.3% male). At diagnosis, 95.5% were receiving ART and 91.3% had undetectable viral load, with median CD4 count of 569 cells/μL. One hundred thirty-eight patients (78.4%) had symptoms, 44 (25%) developed RF and 53 (31%) developed bilateral pneumonia. The most commonly used treatments were: steroids (26.7%) and hydroxychloroquine (13.1%). When comparing patients with and without RF, we found statistically significant differences for 20 of the analyzed variables such as age (
< .001) and CD4 (
0.002), and route of HIV transmission by intravenous drug users IVDU (
0.002) were determined. In multivariate analysis, age odds ratio (OR) 1.095 and CD4 count less than 350 cells/μL (OR 3.36) emerged as risk factor for RF. People living with HIV whose CD4 count is <350 cells are at higher risk of developing RF when infected by SARS-CoV-2.
Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of ...morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.
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