Antiretroviral Therapy For HIV Infection Research Articles

Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting "block and lock" treatment strategies.

Current antiretroviral therapy for HIV-1 infection does not represent a cure for infection as viral rebound inevitably occurs following discontinuation of treatment. The "block and lock" therapeutic strategy is intended to enforce proviral latency and durably suppress viremic reemergence in the absence of other intervention. The transcription-associated cyclin-dependent protein kinases (tCDKs) are required for expression from the 5´ HIV-1 long-terminal repeat, but the therapeutic potential of inhibiting these kinases for enforcing HIV-1 latency has not been characterized. Here, we expanded previous observations to directly compare the effect of highly selective small molecule inhibitors of CDK7 (YKL-5-124), CDK9 (LDC000067), and CDK8/19 (Senexin A), and found each of these prevented HIV-1 provirus expression at concentrations that did not cause cell toxicity. Inhibition of CDK7 caused cell cycle arrest, whereas CDK9 and CDK8/19 inhibitors did not, and could be continuously administered to establish proviral latency. Upon discontinuation of drug administration, HIV immediately rebounded in cells that had been treated with the CDK9 inhibitor, while proviral latency persisted for several days in cells that had been treated with CDK8/19 inhibitors. These results identify the mediator kinases CDK8/CDK19 as potential "block and lock" targets for therapeutic suppression of HIV-1 provirus expression.

Enriching Data Science and Health Care Education: Application and Impact of Synthetic Data Sets Through the Health Gym Project.

Large-scale medical data sets are vital for hands-on education in health data science but are often inaccessible due to privacy concerns. Addressing this gap, we developed the Health Gym project, a free and open-source platform designed to generate synthetic health data sets applicable to various areas of data science education, including machine learning, data visualization, and traditional statistical models. Initially, we generated 3 synthetic data sets for sepsis, acute hypotension, and antiretroviral therapy for HIV infection. This paper discusses the educational applications of Health Gym's synthetic data sets. We illustrate this through their use in postgraduate health data science courses delivered by the University of New South Wales, Australia, and a Datathon event, involving academics, students, clinicians, and local health district professionals. We also include adaptable worked examples using our synthetic data sets, designed to enrich hands-on tutorial and workshop experiences. Although we highlight the potential of these data sets in advancing data science education and health care artificial intelligence, we also emphasize the need for continued research into the inherent limitations of synthetic data.

An evaluation of Mp1p antigen screening for talaromycosis in HIV-infected antiretroviral therapy-naïve population in Guangdong, China.

Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis. We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People's Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/μl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977-0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/μl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/μl was superior to that in those with higher CD4+ counts. Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed.

Hypertension in people living with HIV on combined antiretroviral therapy in rural Tanzania.

Exposure to anti-retroviral therapy in HIV infection has been associated with hypertension, but whether and to what extent HIV-related factors and anti-retroviral treatment contribute to hypertension is not well defined; in addition, data are particularly scarce in Sub-Saharan Africa. Aim of the study was to investigate prevalence and awareness of hypertension in a cohort of people living with HIV (PLWHIV) on anti-retroviral therapy in rural Tanzania, and to identify possible predictors of hypertension. A cross-sectional study on hypertension in PLWHIV was conducted at Tosamaganga District Hospital, Iringa Region, Tanzania. Subjects on anti-retroviral therapy, age 26-80 years and with monthly attendance to the HIV clinic, were considered eligible. A total number of 242 patients were included in the analysis. Sixty-two subjects (26%) had hypertension, the majority (77%) of them not aware of the condition and/or not on treatment. Older age, higher BMI and lower baseline T-CD4 count were predictors of hypertension at multivariate analysis. The results of the study suggest that hypertension screening should become part of ordinary care of PLWHIV in Tanzania, particularly in subjects with more severe immunosuppression. Leveraging already existing HIV services could be an option to prevent the burden of non-AIDS complication and related deaths.

Fee for home delivery and monitoring of antiretroviral therapy for HIV infection compared with standard clinic-based services in South Africa: a randomised controlled trial

Home delivery and monitoring of antiretroviral therapy (ART) is convenient, overcomes logistical barriers, and could increase individual ART adherence and viral suppression. With client payment and sufficient health benefits, this strategy could be scalable. The aim of the Deliver Health Study was to test the acceptability and efficacy of a user fee for home ART monitoring and delivery. We conducted a randomised trial, the Deliver Health Study, of a fee for home delivery of ART compared with free clinic ART delivery in South Africa. People with HIV who were 18 years or older and clinically stable (including CD4 count >100 cells per μL and WHO HIV stage 1-3) were randomly assigned to: (1) fee for home delivery and monitoring of ART, including community ART initiation if needed; or (2) clinic-based ART (standard of care). The one-time fee for home delivery (ZAR 30, 60, and 90; equivalent to US$2, 4, 6) was tiered on the basis of participant income. The primary outcomes were recorded fee payment and acceptability assessed via questionnaire. The key virological secondary outcome was viral suppression with the difference between study groups assessed through robust Poisson regression including participants with viral load measured at exit (modified intention-to-treat analysis). This trial is registered on ClinicalTrials.gov (NCT04027153) and is complete, with analyses ongoing. From Oct 7, 2019, to Jan 30, 2020, 162 participants were enrolled; 82 were randomly assigned to the fee for home delivery group and 80 to the clinic-based group, with similar characteristics at baseline. Overall, 87 (54%) participants were men, 101 (62%) were on ART, and 98 (60%) were unemployed. In the home delivery group, 40 (49%), 33 (40%), and nine (11%) participants qualified for the ZAR 30, 60, and 90 fee, respectively. Median follow-up was 47 weeks (IQR 43-50) with 96% retention. 80 (98%) participants paid the user fee, with high acceptability and willingness to pay. In the modified intention-to-treat analysis of 155 (96%) participants who completed follow-up, fee for home delivery and monitoring statistically significantly increased viral suppression from 74% to 88% overall (RR 1·21, 95% CI 1·02-1·42); and from 64% to 84% among men (1·31, 1·01-1·71). Among South African adults with HIV, a fee for home delivery and monitoring of ART significantly increased viral suppression compared with clinic-based ART. Clients' paying a fee for home delivery and monitoring of ART was highly acceptable in the context of low income and high unemployment, and improved health outcomes as a result. Home ART delivery and monitoring, potentially with a user fee to offset costs, should be evaluated as a differentiated service delivery strategy to increase access to care. National Institutes of Mental Health.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME CAUSED BY TWO SPECIES OF NONTUBERCULOUS MYCOBACTERIA PRESENTING AS MEDIASTINAL LYMPHADENOPATHY

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME CAUSED BY TWO SPECIES OF NONTUBERCULOUS MYCOBACTERIA PRESENTING AS MEDIASTINAL LYMPHADENOPATHY

Health-related quality of life of children and adolescents living with HIV in Lagos, Nigeria: a cross-sectional study.

Introductionadolescents living with HIV [ALHIV] face the dual challenges of adolescence and coping with HIV infection. This study aims to evaluate health-related quality of life [HRQoL] of children and adolescents aged 8 - 18 years living with HIV in an HIV treatment centre in Lagos, Nigeria.Methodswe conducted a cross-sectional study among children and adolescents living with HIV and receiving antiretroviral therapy. HRQoL was assessed using the Paediatric Quality of Life Inventory [PedQoL™]. Socio-demographic data and HIV related clinical and laboratory characteristics were also obtained and tested based on HRQoL scores in order to determine if there were possible associations.Resultsthe study included 113 participants with a mean age of 14 (± 2.9) years. There was male predominance, with a male: female sex ratio of 1.1: 1. The mean duration of ART was 102.9 (±36.9) months and CD4 lymphocyte count was and 741.2 (±335.7) cell/mm3. The majority of participants (62%) were also virally suppressed. Based on self-reported data, the mean physical, psychosocial and total HRQoL scores were 85.0 [± 22.4], 78.5 [±17.5] and 81.6 [±18.4] respectively. Adolescents aged 13-18 years had significantly higher scores than children aged 8-12 years. Male patients who had been on ART for ≥60 months were also significantly associated with higher HRQoL scores (OR=5.46 [CI= 2.24-13.29], p = 0.0009) and OR= 4.80, [CI= 1.58 - 14.56] p = 0.0032).Conclusionthe majority of participants in the study had good HRQoL scores, attesting to the success of highly active antiretroviral therapy for HIV infection and the ease of access and availability to a comprehensive care.

Initiation of Rapid Antiretroviral Therapy in HIV Infection

Initiation of Rapid Antiretroviral Therapy in HIV Infection

COVID-19 in People Living with HIV

PurposeThe current COVID-19 pandemic affects all strata of the population. Particular interest is the study of the course of this pathology in people with comorbidity.The purpose of our research is to study the features of the course of a COVID-19 people living with HIV (PLHIV).Methods & MaterialsWe conducted a retrospective analysis of the epidemiological, clinical and laboratory data of 121 patients with HIV infection treated for COVID-19 in 2020. Among PLHIVS, 87.6% were treated with antiretroviral therapy for HIV infection an average of 5.8 years.ResultsIt was found that 45.5% were women and 54.5% were men. The average age was 41 years old (IQR: 20-78 years). The greatest number of cases was observed among both men and women in the age category of 30-49 years (74.2% and 72.7%, respectively). In the studied group, in 63.4%, in addition to HIV infection, patients suffered from other concomitant diseases, the most frequent of which were chronic lung diseases (22.3%), hypertension (18.2%), metabolic disorders (13.2%). In all cases, the COVID-19 disease occurred with a clinical manifestation. The most common symptoms were fever (76.0%), cough (63.6%) and sore throat (56.2%), loss of taste and smell was detected in 49.6% of cases. In 48.8%, COVID-19 in PLHIV was mild. In 88.1%, the duration of the disease did not exceed 14 days. Moderate forms were noted in 40.5% of cases. 10.7% of cases have severe form of COVID-19. The fatal outcomes were recorded in 8 patients, while in the group of patients receiving antiretroviral therapy, the mortality rate was 3.8%, and in the group without antiretroviral therapy therapy - 26.7%.ConclusionWe estimated that the proportion of deaths in patients with HIV infection is higher than in the general population (2.2%). PLHIV are a vulnerable group in relation to the risk of death from COVID-19.

Erythropoietin and iron for anemia in HIV-infected patients undergoing maintenance hemodialysis in China: a cross-sectional study

BackgroundAnemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China.MethodsThis cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann–Whitney U test, and chi-square statistics were applied in SPSS.ResultsThe Hgb of HIV-HD and HD groups were 105.70 (95.93–112.08) g/L and 112.00 (93.00–126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38–589.75) ng/ml and 272.70 (205.00–434.00) ng/ml in HIV-HD and HD groups respectively.ConclusionsA higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.

POS-625 ERYTHROPOIETIN AND IRON FOR ANEMIA IN HIV-INFECTED PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS IN CHINA

Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China. This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4+ T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann-Whitney U test, and chi-square statistics were applied in SPSS. The Hgb of HIV-HD and HD groups were 105.70 (95.93-112.08) g/L and 112.00 (93.00-126.00) g/L respectively (P=0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55±115.47 U/kg/week) compared to the HIV-negative HD group (161.86±110.31 U/kg/week) (P=0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P=0.003). The ferritin levels were 316.50 (117.38-589.75) ng/ml and 272.70 (205.00-434.00) ng/ml in HIV-HD and HD groups respectively. A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.

Levels and correlates of physical activity and capacity among HIV-infected compared to HIV-uninfected individuals.

IntroductionIn the HIV-infected individuals, physical activity improves physical strength, quality of life and reduces the risk of developing non-communicable diseases. In Sub-Saharan Africa, HIV-infected patients report being less active compared to HIV-uninfected individuals. We assessed the levels and correlates of objectively measured physical activity and capacity among HIV-infected antiretroviral therapy (ART)-naive individuals compared to HIV-uninfected individuals in Mwanza, Tanzania.MethodWe conducted a cross-sectional study among newly diagnosed HIV-infected ART-naive individuals and HIV-uninfected individuals frequency-matched for age and sex. Socio-demographic data, anthropometrics, CD4 counts, haemoglobin level, and C-reactive protein (CRP) were collected. Physical activity energy expenditure (PAEE) was assessed as measure of physical activity whereas sleeping heart rate (SHR) and grip strength were assessed as measures of physical capacity. Multivariable linear regression was used to assess the correlates associated with physical activity and capacity.ResultsA total of 272 HIV-infected and 119 HIV-uninfected individuals, mean age 39 years and 60% women participated in the study. Compared to HIV-uninfected individuals, HIV-infected had poorer physical activity and capacity: lower PAEE (-7.3 kj/kg/day, 95% CI: -11.2, -3.3), elevated SHR (7.7 beats/min, 95%CI: 10.1, 5.3) and reduced grip strength (-4.7 kg, 95%CI: -6.8, -2.8). In HIV-infected individuals, low body mass index, moderate-severe anaemia, low CD4 counts and high CRP were associated with lower physical activity and capacity. In HIV-uninfected individuals, abdominal obesity and moderate anaemia were associated with lower physical activity and capacity.ConclusionHIV-infected participants had lower levels of physical activity and capacity than HIV-uninfected participants. Correlates of physical activity and capacity differed by HIV status. Management of HIV and related conditions needs to be provided effectively in health care facilities. Interventions promoting physical activity in these populations will be of importance to improve their health and reduce the risk of non-communicable diseases.

Renal function and associated mortality risk in adults commencing HIV antiretroviral therapy in Zimbabwe.

People with HIV (PWH) in sub-Saharan Africa appear to have a higher incidence of renal disease than other global regions but data are limited. This renal impairment may be associated with an increased mortality risk. To define the prevalence of renal disease and explore its association with mortality risk in a cohort from Zimbabwe commencing antiretroviral therapy (ART) for HIV infection. A retrospective study of all patients aged at least 18 years, commenced on ART for HIV infection at the Newlands Clinic in Harare, Zimbabwe between January 2007 and September 2019 was conducted. Data were extracted from electronic medical records. Patients with no baseline creatinine measurement were excluded. Baseline characteristics were assessed as potential predictors for mortality by Cox proportional hazard regression. Three thousand and thirty-nine patients were eligible for inclusion. Most were female (62.1%), with a median age of 36 years (IQR 30-43). At baseline, 7.3% had an estimated glomerular filtration rate (eGFR) 90 ml/min per 1.73 m2 or less and 11.4% had proteinuria. Over a median follow-up period of 4.6 years (IQR 2.5-6.9), the mortality rate was 8.7%. One half of deaths (49.2%) occurred within the first year. In multivariable analysis, a baseline eGFR between 60 and 90 ml/min per 1.73 m2 [hazard ratio 2.22, 95% confidence interval (CI) 1.46-3.33, P < 0.001] and proteinuria (hazard ratio 2.10, 95% CI 1.35-3.27, P < 0.001) were associated with increased mortality risk. Baseline renal impairment was common. Both a reduced eGFR or proteinuria were independently associated with a doubling of mortality risk. These should serve as markers in the clinical setting of at-risk patients.

The analysis of the availability of fixed-dose combinations in antiretroviral therapy for HIV infection in the Russian Federation

To analyze the features of drugs provision for special groups of treatment-nave HIV-infected patients initiating antiretroviral treatment with fixed dose combination (FDC) for once-daily single-tablet regimen, in Russian healthcare setting. We studied the regulatory legal documents governing the provision of antiretroviral drugs in Russia and analyzed the Russian Program of State Guarantees to determine the inclusion of the investigated FDCs in the lists of regional benefits, as well as regional and federal procurement of these drugs in 2020 and 2021. We compared costs of first line therapy for special groups using FDCs regimens per year in case of regional purchases or centralized purchases. It was show that doravirin/tenofovir/lamivudine was the least expensive in 2020 and in 2021 among new FDCs form drugs. Worth 325.8 and 323.9 thousand rubles. per patient per year. The most expensive was bictegravir/tenofovir alafenamide/emtricitabine (401.6 and 439.9 thousand rubles, respectively). In case of Ministry of Health centralized purchases, the costs of new FDCs (doravirin/tenofovir/lamivudine and bictegravir/tenofovir alafenamide/emtricitabine), included in Vital and Essential drug list (VEDL) in 2022, will amount to 151,2 and 191.4 thousand rubles respectively, which is 52.9% and 40.4% lower than the cost per course of rilpivirine/tenofovir/emtricitabine. The inclusion of new effective and economical FDCs the whole scheme in one tablet once-daily in VEDL, expands the possibilities of simplify and effective first-line therapy for special groups of HIV-infected patients, as well as reduce the financial burden on the Program of State Guarantees budget and increases treatment coverage. All of this corresponds to the goals of the State Strategy to Combat the Spread of HIV in Russian Federation.

Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection

BackgroundBlood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD.MethodsWe determined BBB integrity by measuring cerebrospinal fluid (CSF)/plasma albumin ratios in archived CSF samples prior to and after initiation of ART in longitudinally-followed neuroasymptomatic HIV-1-infected individuals and patients with HAD. We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of β2-micoglobulin, neopterin, and neurofilament light chain protein (NfL).ResultsWe included 159 HIV-infected participants; 82 neuroasymptomatic individuals and 77 with HAD. All neuroasymptomatic individuals (82/82), and 10/77 individuals with HAD, were longitudinally followed with a median (interquartile range, IQR) follow-up of 758 (230–1752) days for the neuroasymptomatic individuals, and a median (IQR) follow-up of 241 (50–994) days for the individuals with HAD. Twelve percent (10/82) of the neuroasymptomatic individuals and 80% (8/10) of the longitudinally-followed individuals with HAD had elevated albumin ratios at baseline. At the last follow-up, 9% (7/82) of the neuroasymptomatic individuals and 20% (2/10) of the individuals with HAD had elevated albumin ratios. ART significantly decreased albumin ratios in both neuroasymptomatic individuals and in patients with HAD.ConclusionThese findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.

Prevalence and factors associated with fertility desire among people living with HIV: A systematic review and meta-analysis.

BackgroundThe fertility desire of people living with HIV (PLHIV) has been rising in the past decade. However, there are many studies among which the association remains controversial between the fertility desire of HIV-infected persons and antiretroviral therapy (ART), sex, marital status, and educational level.MethodsWe performed a literature search of these meta-analyses in PubMed, the Cochrane Library, Web of Science and ScienceDirect in November 2019. We also reviewed references of eligible studies to complement the search. We used pooled odds ratios (ORs) and 95% confidence intervals (CIs) with a random-effects model and a fixed-effects model to estimate the association between fertility desire among PLHIV and ART, sex, age, marital status, educational level, and number of children. Subgroups with I square values (I2) and sensitivity analyses were performed to assess the heterogeneity and the stability of the overall ORs, respectively. We evaluated publication bias using Egger’s test and a visual inspection of the symmetry in funnel plots.ResultsIn these meta-analyses 50 articles were included with 22,367 subjects. The pooled prevalence of fertility desire among PLHIV was estimated to be 42.04%. The pooled analyses showed that the fertility desire of PLHIV is associated with ART (OR = 1.11, 95% CI:1.00–1.23, P = 0.043), sex (OR = 1.51, 95% CI:1.10–2.09), age (OR = 2.65, 95% CI:2.24–3.14), marital status (OR = 1.34, 95% CI:1.08–1.66), educational level (OR = 0.85, 95% CI:0.73–1.00, P = 0.047) and the number of children (OR = 3.99, 95% CI:3.06–5.20). PLHIV who are on ART, are male, are younger than 30, are married/cohabiting, have received a secondary education or above, and are childless have a higher prevalence of fertility desire. The two factors of age and the number of children, in particular demonstrated a strong significant association with fertility desire. We found moderate heterogeneity in the meta-analyses of age and educational level and high heterogeneity in the meta-analyses of sex, marital status and number of children. Publication bias was detected in the meta-analyses of the association of fertility with sex and educational level.ConclusionThis study demonstrates that the prevalence of fertility desire among HIV-infected people is 42.04%, and the fertility desire among PLHIV is associated with ART experience, sex, age, marital status, the number of children, and educational level. Since a majority of PLHIV are of reproductive age, it is necessary to support PLHIV in terms of their needs regarding reproductive decision-making. Through counseling and reproductive health care, further measures to prevent the horizontal and vertical transmission of HIV should be taken.

Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma.

Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5–100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson’s correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment.

Autoantibodies Among HIV-1 Infected Individuals and the Effect of Anti-Retroviral Therapy (ART) on It.

Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 were 4%, 1% and 3% among ART naïve, treated and controls, respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre, respectively (p<0.05). ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.

Plasma Lipidomic Profiles and Risk of Diabetes: 2 Prospective Cohorts of HIV-Infected and HIV-Uninfected Individuals.

Antiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection. We profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35 to 55 years from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years). We identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (P < 0.05 after FDR correction). After adjustment for multiple covariates, cholesteryl ester (CE) (22:4), lysophosphatidylcholine (LPC) (18:2), phosphatidylcholine (PC) (36:4), phosphatidylcholine plasmalogen (34:3), and phosphatidylethanolamine (PE) (38:2) were associated with decreased risk of diabetes (HRs = 0.70 to 0.82 per SD increment), while diacylglycerol (32:0), LPC (14:0), PC (38:3), PE (36:1), and triacylglycerol (50:1) were associated with increased risk of diabetes (HRs = 1.26 to 1.56 per SD increment). HIV serostatus did not modify any lipid-diabetes associations; however, most of these lipid species were positively associated with HIV and/or ART use, including 3 diabetes-decreased ( CE [22:4], LPC [18:2], PE [38:2]) and all 5 diabetes-increased lipid species. This study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.

Occult hepatitis B virus infection in a Kenyan cohort of HIV infected anti-retroviral therapy naïve adults.

Occult hepatitis B virus (HBV) infection (OBI) is a phase of HBV infection characterised by the presence of HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg). OBI is of concern in the HIV-infected due to high prevalence and risk of HBV reactivation. The prevalence and clinico-demographic characteristics of OBI in anti-retroviral therapy (ART) naïve HIV infected adults in Kenya is unknown. A cross sectional study carried was out at three sites in Kenya. HIV infected ART naïve adults were enrolled and demographic data collected. Blood samples were assayed for HBsAg, HBV DNA, alanine aminotransferase, aspartate aminotransferase, antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). Data on CD4 count, HIV viral load and platelet count were obtained from medical records. Of 208 patients, 199 (95.7%) did not report HBV vaccination, 196 (94.2%) were HBsAg negative, 119 (57.2%) had no HBV markers, 58 (27.9%) had previous HBV infection (anti-HBc positive) and 11 (5.3%) had OBI. All 11 (100%) OBI patients were anti-HBc positive. OBI patients comprised 19.0% of HBsAg negative, anti-HBc positive patients. There was no difference in clinico-demographic characteristics between the overt HBV, OBI and HBV negative patients. This was the first study on OBI in ART naïve HIV infected adults in Kenya. The lower OBI prevalence compared to other sub-Saharan African countries could be attributed to lower HBV exposure. Most patients were HBV unexposed and unimmunized, outlining the need to implement guideline recommended immunization strategies.