Active Antiretroviral Therapy Research Articles

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. PROSPERO (CRD42021255508).

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Adverse Drug Reactions in HIV/AIDS Patients on Highly Active Antiretro Viral Therapy: A Review of Prevalence

Antiretroviral therapy (ART) is associated with a variety of side effects, ranging from mild intolerance to lifethreatening side effects. Short-term adverse reactions include nausea, vomiting, diarrhea, rash, hypersensitivity reactions, urticarial reactions, erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome, infection liver toxicity, drowsiness and vivid dreams. Long-term side effects include lipodystrophy, lipoatrophy, dyslipidemia, diabetes, and skin, nail, and hair abnormalities. When starting ART, HIV-infected patients may frequently experience a variety of side effects such as rash, hair loss, hypersensitivity syndrome reactions, urticaria or erythema multiforme, Stevens-Johnson syndrome, known as manifested by a short-term course of side effects. A large number of patients have abnormal blood sugar and lipid profiles when using all groups of ARV drugs despite their relatively young age; Hyperlipidemia has been associated with HIV PI use and is more common and more severe than hyperlipidemia in HAART-naïve patients. Dyslipidemia, hyperglycemia, and lipodystrophy are cardiovascular risk factors in these patients. Hypertension is associated with established risk factors and is common in HIV-infected individuals. However, long-term use of HAART/ARV is necessary to control HIV infection. Keywords: prevalence, adverse drug reaction, HIV, AIDS, HAART

Viral suppression rate at operation triple zero (Otz) and regular art follow-Up programs and associated factors among adolescent clients of Addis Ababa Ethiopia: a comparative cross-sectional study

Background- Viral suppression is the main goal of currently available treatment and it is used as a primary indicator of successful treatment for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). This ensures a reduction in AIDS-associated morbidity and mortality and decreases the risk of both vertical and horizontal viral transmission. This study aimed to investigate the magnitude of viral suppression and its associated factors among adolescents, comparing the operation triple zero (OTZ) program to regular antiretroviral therapy (ART) follow-up programs.Methods- The research consisted of a comparative cross-sectional study, which included a total sample size of 446 adolescents on Active Antiretroviral Therapy (ART) — 223 enrolled in OTZ, and 223 in regular ART from public hospitals. Sociodemographic data were obtained using a self-administered semi-structured questionnaire, and clinical data were extracted from medical records. To examine the prevalence of viral suppression (VS) the latest status was used and multivariate logistic regression analysis was performed to identify factors associated with VS.Results- Overall, the adolescent viral suppression was 88.3%, with 92.4% in the OTZ group and 84.3% in the regular ART group. Among OTZ participants, the factors that significantly reduced the odds of viral suppression were having a history of admission in the last year, alcohol use, biological mother not alive, cigarette smoking, social discrimination, and current medication regimen TDF/3TC/EFZ. Among those in regular ART, factors associated with a lesser chance of viral suppression were alcohol use, social discrimination, unscheduled appointments, and current medication regimen TDF/3TC/EFZ when compared to their counterparts. When we compared the two programs, OTZ had a 26.1 times greater chance of suppressing HIV viral load (AOR = 26.1, 95% CI: 3.499–133.9; P = 0.041).Conclusion- The overall VS was 88.3%, while viral suppression is better achieved through the OTZ program than through regular ART services. Alcohol use, biological mother not alive, cigarette smoking, social discrimination, and current medication regimen TDF/3TC/EFZ were identified to be factors associated with viral nonsuppression. Therefore, it is advisable to implement the OTZ program in all HIV care centers and focus on factors reducing viral suppression.

Assessment of regional body composition, physical function and sarcopenia among peruvian women aging with HIV: A cross-sectional study.

Management of chronic conditions and optimization of overall health has become a primary global health concern in the care of people living with HIV in the era of highly active antiretroviral therapy (ART), particularly in lower-and-middle income countries where infrastructure for chronic disease management may be fragmented. Alterations in body composition can reflect important changes in musculoskeletal health, particularly among populations at risk for developing fat and muscle redistribution syndromes, such as women with HIV on ART. Given the lack of data on this topic in Latin America and the Caribbean, we designed an exploratory study to measure these outcomes in a population of women aging with HIV in Peru. We conducted a cross-sectional study among Peruvian women with and without HIV aged ≥40 years. Dual X-ray absorptiometry was used to measure trunk and limb lean mass (LM) and fat mass (FM). Physical performance was assessed with the Short Physical Performance Battery (SPPB) and physical strength with a dynamometer. Sarcopenia was assessed based upon EWGSOP criteria. We used linear regression to model associations between body composition, sarcopenia and physical performance scores. 104 women with HIV and 212 women without HIV were enrolled (mean age 52.4±8.2 vs. 56.4±8.8 years, p≤0.001). Among women with HIV, mean years since diagnosis was 11.8±6 and all were on ART. Mean SPPB score was 9.9 vs 10.8 (p<0.001) between both groups. Sarcopenia spectrum was found in 25.9% and 23.1%, respectively. In the multivariable regression analysis, trunk FM and older age were negatively correlated with physical performance among women with HIV. Severe sarcopenia was found among a greater proportion of those with HIV (3.8% vs. 0.9%, p = 0.84), however this finding was not statistically significant. Women with HIV had significantly lower SPPB scores compared to women without HIV, and trunk FM and upper limb LM were independent predictors for the SPPB and Grip Strength tests, respectively. Larger, prospective studies are needed in Latin America & the Caribbean to identify individuals at high risk for sarcopenia and declines in physical function, and to inform prevention guidelines.

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients.

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

Pharmacokinetic Model of Tenofovir and Emtricitabine and Their Intracellular Metabolites in Patients in the ANRS 134-COPHAR 3 Trial Using Dose Records.

Tenofovir (TFV) and emtricitabine (FTC) are part of the recommended highly active antiretroviral therapy (ART). Both molecules show a large interindividual pharmacokinetic (PK) variability. Here, we modeled the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV diphosphate [TFV-DP] and FTC triphosphate [FTC-TP]) collected after 4 and 24 weeks of treatment in 34 patients from the ANRS 134-COPHAR 3 trial. These patients received daily (QD) atazanavir (300 mg), ritonavir (100 mg), and a fixed-dose combination of coformulated TFV disoproxil fumarate (300 mg) and FTC (200 mg). Dosing history was collected using a medication event monitoring system. A three-compartment model with absorption delay (Tlag) was selected to describe the PK of, respectively, TFV/TFV-DP and FTC/FTC-TP. TFV and FTC apparent clearances, 114 L/h (relative standard error [RSE] = 8%) and 18.1 L/h (RSE = 5%), respectively, were found to decrease with age. However, no significant association was found with the polymorphisms ABCC2 rs717620, ABCC4 rs1751034, and ABCB1 rs1045642. The model allows prediction of TFV-DP and FTC-TP concentrations at steady state with alternative regimens.

Independent Effects of HIV and Antiretroviral Therapy on the Oral Microbiome Identified by Multivariate Analyses.

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched HIV- subjects) showed a significant effect on both the bacteriome and mycobiome (P < 0.024) after controlling for other clinical variables (permutational multivariate analysis of variance [PERMANOVA] of Bray-Curtis dissimilarity). Cross-sectional analyses evaluating the effects of ART (HIV+ ART+ versus HIV+ ART- subjects) revealed a significant effect on the mycobiome (P < 0.007) but not the bacteriome. In parallel longitudinal analyses, ART (before versus after the initiation of ART) had a significant effect on the bacteriome, but not the mycobiome, of HIV+ and HIV- PrEP subjects (P < 0.005 and P < 0.016, respectively). These analyses also revealed significant differences in the oral microbiome and several clinical variables between HIV- PrEP subjects (pre-PrEP) and the HIV-matched HIV- group (P < 0.001). At the species level, a small number of differences in both bacterial and fungal taxa were identified within the effects of HIV and/or ART. We conclude that the effects of HIV and ART on the oral microbiome are similar to those of the clinical variables but collectively are modest overall. IMPORTANCE The oral microbiome can be an important predictor of health and disease. For persons living with HIV (PLWH), HIV and highly active antiretroviral therapy (ART) may have a significant influence on their oral microbiome. We previously reported a significant effect of HIV with ART on both the bacteriome and mycobiome. It was unclear whether ART added to or masked further effects of HIV on the oral microbiome. Hence, it was important to evaluate the effects of HIV and ART independently. For this, multivariate cross-sectional and longitudinal oral microbiome analyses (bacteriome and mycobiome) were conducted within the cohort, including HIV+ ART+ subjects and HIV+ and HIV- (preexposure prophylaxis [PrEP]) subjects before and after the initiation of ART. While we report independent significant effects of HIV and ART on the oral microbiome, we conclude that their influence is similar to that of the clinical variables but collectively modest overall.

Impaired response of memory Treg to high density lipoproteins is associated with intermediate/high cardiovascular disease risk in persons with HIV.

Cardiovascular disease (CVD) is a leading cause of enhanced morbidity and mortality in persons with HIV (PWH) in the era of highly active antiretroviral therapy (AART). However, the underlying mechanisms are not fully understood. Regulatory T cells (Treg), notably the highly suppressive memory subset, have been shown to limit CVD. Importantly, memory Treg cell numbers remain low in many treated PWH. High density lipoproteins (HDL) also protect from CVD, and we previously found that Treg-HDL interactions reduce oxidative stress in these cells. Here, we evaluated Treg-HDL interactions in PWH and whether they were operative in those higher CVD risk. To do that, we recruited a cohort of PWH with intermediate/high CVD risk (median ASCVD risk score of 13.2%, n=15) or low/borderline risk (median ASCVD risk score of 3.6%, n=14), as well as a group of statins treated PWH with intermediate/high CVD risk (median ASCVD risk score of 12.7%, n=14). We evaluated Treg frequency, phenotype and response to HDL. PWH with Int/High CVD risk had a significantly lower number of memory Treg, but memory Treg were more activated and displayed an inflammatory phenotype, versus those with Low/BL CVD risk. In untreated patients, Treg absolute numbers were negatively correlated with ASCVD score. Although HDL decreased oxidative stress in memory Treg in all subjects, memory Treg from PWH with Int/High CVD risk were significantly less responsive to HDL than those from PWH with Low/BL CVD risk. The level of oxidative stress in memory Treg positively correlated with ASCVD scores. In contrast, plasma HDL from PWH, regardless of CVD risk, retained their anti-oxidative properties, suggesting that the defect in memory Treg response to HDL is intrinsic. Statin treatment partially ameliorated the memory Treg defect. In conclusion, the defective HDL-Treg interactions may contribute to the inflammation-induced increased CVD risk observed in many AART-treated PWH.

Prevalence of anemia among HIV-infected individuals and the associated factors: A single-center, retrospective review of 513 cases

Background: Although a major public health problem around the world, the prevalence of anemia and the associated factors in HIV-infected individuals remains understudied in the Indian context. Objectives: The objective was to assess the prevalence of anemia and the associated factors among HIV-infected individuals. Methods: The records of 513 HIV-affected individuals (M: F: 244:269) aged 12 to 84 years (mean ± SD: 37.5 ± 12.1) were reviewed retrospectively for the presence of anemia and the associated factors. The anemia was defined and severity was graded per the WHO guidelines. Results: Anemia of variable severity was present in 77.7% of the individuals. The female sex(OR: 2.09; Cl: 95%; CI: 1.41–3.10; p &lt; 0.05), CD4+ count ≤ 200 cells/microliter (OR: 2.36; Cl: 95%; CI: 1.59–3.52; p &lt; 0.0001), WBC count &lt; 4000 cells/mm3 (OR: 3.29; Cl: 95%; CI: 0.97–11.14; p &lt; 0.04), platelet count &lt; 100,000 cells/dL (OR: 0.50; Cl: 95%; CI: 0.31–0.81; p &lt; 0.05), before ART (OR: 3.78; Cl: 95%; CI: 2.91–4.91; p &lt; 0.0001), and tuberculosis treatment (OR: 5.88; Cl: 95%; CI: 1.38–25.04; p &lt; 0.05) were factors significantly associated with anemia. The mean duration of highly active antiretroviral therapy (ART) was 3.15 years, with 395 (77%) individuals being on treatment for ≤ five years. ART significantly improved hemoglobin levels (p &lt; 0.0001). Conclusion: Anemia of variable severity remains a significant co-morbidity among HIV-infected individuals, especially females, prior to the initiation of ART, and those with a low CD4+ count or thrombocytopenia and on anti-tuberculosis treatment. The fact that this was a single-center study, its small number of subjects, the retrospective design, and no information on red blood cell indices and the viral load were its important limitations. Key words: AIDS; anemia; ART; CD4+ count; HAART; HIV; India

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

The virological consequences of low-level viraemia

With highly active antiretroviral therapy (ART), people living with HIV can achieve and maintain viral suppression below a detectable level, preventing transmission of HIV and AIDS-related mortality.1,2 However, persistent low-level viraemia (usually defined as plasma HIV-RNA between 50 copies per mL to below the threshold for virological failure) occurs among some people living with HIV receiving ART.3–5 Despite its occurrence, the clinical significance and management of low-level viraemia remains unclear,3,5,6 particularly with dolutegravir-based ART regimen.

Exploring the barriers to the antiretroviral therapy adherence among people living with HIV in Bangladesh: A qualitative approach.

IntroductionSince the evolution of highly active antiretroviral therapy (ART), a near-perfect ART adherence level (>95%) is needed to control viral suppression. Non-adherence to treatment may lead to acquired immunodeficiency syndrome (AIDS) and drug resistance. Though the Bangladesh government provides free treatment and counselling services to people living with human immunodeficiency virus (PLHIV), only 22% of the identified PLHIV continue treatment. Therefore, this study aims to explore the barriers that obstruct the Bangladeshi PLHIV to ensure ART adherence.MethodsWe conducted a qualitative study in Dhaka, Bangladesh, and recruited the sensitive study population following non-probability, mainly purposive sampling from a community-based registered organization for PLHIV. We conducted the in-depth interview using a semi-structured guideline with 15 consented respondents. We transcribed the audio-recorded interviews in the local language (Bangla) and then translated those into English for data analysis. During the data extraction process, the lead and corresponding authors independently extracted raw data to generate different themes and sub-themes and invited other authors to contribute when they could not solve any discrepancies.ResultsThe study identified three significant categories of barriers at the individual, community, and institutional levels that negatively interfered with ART adherence. The most dominant barriers were discrimination and rejection related to stigma, as almost all participants mentioned these barriers. Stigmatizing attitudes and the discriminatory act of the community people and healthcare providers critically affected their treatment adherence. Other leading barriers were improper inventory management of ART-related medicines and CD4 tests and lack of proper counselling. In addition, we found that a positive approach toward life and family support motivated some respondents to overcome the barriers.ConclusionsWe recommended strengthening Bangladesh’s HIV/AIDS prevention, treatment, and management program with a special focus on the improvement of the supply chain of ART-related medicines and CD4 tests and ensuring proper counselling. In addition, we recommended strengthening the behaviour change communication and IEC activities at a large scale to destigmatize health facilities and community levels.

Development and validation of a risk prediction model for lost to follow-up among adults on active antiretroviral therapy in Ethiopia: a retrospective follow-up study

BackgroundOver 420,000 people have initiated life-saving antiretroviral therapy (ART) in Ethiopia; however, lost-to-follow-up (LTFU) rates continues to be high. A clinical decision tool is needed to identify patients at higher risk for LTFU to provide individualized risk prediction to intervention. Therefore, this study aimed to develop and validate a statistical risk prediction tool that predicts the probability of LTFU among adult clients on ART.MethodsA retrospective follow-up study was conducted among 432 clients on ART in Gondar Town, northwest, Ethiopia. Prognostic determinates included in the analysis were determined by multivariable logistic regression. The area under the receiver operating characteristic (AUROC) and calibration plot were used to assess the model discriminative ability and predictive accuracy, respectively. Individual risk prediction for LTFU was determined using both regression formula and score chart rule. Youden index value was used to determine the cut-point for risk classification. The clinical utility of the model was evaluated using decision curve analysis (DCA).ResultsThe incidence of LTFU was 11.19 (95% CI 8.95–13.99) per 100-persons years of observation. Potential prognostic determinants for LTFU were rural residence, not using prophylaxis (either cotrimoxazole or Isoniazid or both), patient on appointment spacing model (ASM), poor drug adherence level, normal Body mass index (BMI), and high viral load (viral copies > 1000 copies/ml). The AUROC was 85.9% (95% CI 82.0–89.6) for the prediction model and the risk score was 81.0% (95% CI 76.7–85.3) which was a good discrimination probability. The maximum sensitivity and specificity of the probability of LTFU using the prediction model were 72.07% and 83.49%, respectively. The calibration plot of the model was good (p-value = 0.350). The DCA indicated that the model provides a higher net benefit following patients based on the risk prediction tool.ConclusionThe incidence of LTFU among clients on ART in Gondar town was high (> 3%). The risk prediction model presents an accurate and easily applicable prognostic prediction tool for clients on ART. A prospective follow-up study and external validation of the model is warranted before using the model.

LIVER TRANSPLANTATION IN HIV PATIENTS: A CASE SERIES FROM THE NORTHEAST REGION OF BRAZIL.

The emergence of potent combined highly active antiretroviral therapy (ART) in 1996 changed the natural history of HIV infection, with a significant reduction in mortality due to opportunistic infections but increased morbidity due to chronic cardiovascular, hepatic, and renal diseases. In May 2016, a reference center for liver transplantation in the Northeast of Brazil performed the first liver transplantations (LT) in HIV patients, with five others until 2021. The criteria for selection of LT were good adherence and absence of resistance to ART, HIV viral load maximum suppression, T-CD4+ lymphocyte count of more than 100 cells/mm3, and absence of opportunistic infections in the last 6 months. Six liver transplants were performed between May 2016 and May 2021, five men, with a mean age of 53.2 years, and one was a diabetic patient. All patients had access to grafts with short cold ischemia with a mean time of 5 hours and 39 minutes. The 4-month survival rate was 100%, with a range time of follow-up of 4-63 months (mean time of 31 months). The mean pre-transplant T-CD4+ lymphocyte count was 436 cells/mm3. The mean length of hospital stay after transplantation was 16.8 days. One patient presented precocious vena cava thrombosis; another had stenosis of cavocaval anastomosis leading to refractory ascites, renal failure and post-transplant graft dysfunction, and another presented stenosis of choledochal anastomosis. Immunosuppression and prophylaxis were used according to standard protocols, and there were no differences in the profile of infections or rejection after liver transplantation. This case series documents good survival and usual transplant procedures for confirmed HIV cases.

Grave’s Disease as A Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV Patients Who are Later Diagnosed with Cervical Cancer: A Case Report

Grave’s Disease (GD) after giving Active Antiretroviral Therapy (ART) to HIV patients is one of the manifestations of Immune Reconstruction Inflammatory Syndrome (IRIS). Complaints and clinical symptoms of Grave’s IRIS usually appear in 8-33 months since the use of ART. A 40-year-old woman was diagnosed with HIV with comorbid pulmonary tuberculosis (TB) infection. The patient regularly took ART and had finished taking TB drugs for 6 months, and the pulmonary TB was declared cured. However, the patient began to complain and showed clinical symptoms of hyperthyroidism. After receiving anti-thyroid medication, the patient has no complaints related to thyroid disease. Six months later, the patient experienced frequent vaginal bleeding. After being evaluated by the Obstetrics and Gynecology section, the patient was diagnosed with cervical cancer. Abnormality of thyroid function test in HIV patients was common, but only 1-2% of HIV patients showed signs of thyroid disorder. However, few cases still show GD as a manifestation of IRIS in HIV patients receiving ART. Dysregulation of the immune system in IRIS-HIV condition and long-standing inflammatory response of HIV (innate and adaptive immune cells involvement, MCH class I &amp; MCH class II expression, TGFβ effect, immune-modulating drugs effect, and effect of reactive oxygen species) promote progression of cancer. Keywords: Grave Disease, IRIS, Cancer, HIV

Inflammatory and immune markers in HIV-infected older adults on long-term antiretroviral therapy: Persistent elevation of sCD14 and of proinflammatory effector memory T cells.

HIV‐positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared with individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV‐positive subjects. Here, we tested whether the immune correlates of aging, including cell numbers and phenotypes, inflammatory status, and control of human cytomegalovirus (hCMV) in HIV‐positive subjects on long‐term successful ART (HIV+) may reveal increased “immunological age” compared with HIV‐negative, age‐matched cohort (HIV−) in participants between 50 and 69 years of age. Specifically, we expected that younger HIV+ subjects may immunologically resemble older individuals without HIV. We found no evidence to support this hypothesis. While T cells from HIV+ participants displayed differential expression in several differentiation and/or inhibitory/exhaustion markers in different T cell subpopulations, aging by a decade did not pronounce these changes. Similarly, while the HIV+ participants exhibited higher T cell responses and elevated inflammatory marker levels in plasma, indicative of chronic inflammation, this trait was not age‐sensitive. We did find differences in immune control of hCMV, and, more importantly, a sustained elevation of sCD14 and of proinflammatory CD4 and CD8 T cell responses across age groups, pointing towards uncontrolled inflammation as a factor in reduced healthspan in successfully treated older HIV+ patients.

Leiomyosarcoma of the Inferior Vena Cava and Vascular Reconstruction

A 52-years-old female patient infected with human immunodeficiency virus (HIV) presented to the emergency with 20-days intermittent and diffuse abdominal pain radiating to the lower back. The patient had a past medical history of hypertension, noninsulin dependent diabetes mellitus (NIDDM), and HIV with active antiretroviral therapy (HAART) and normal CD4 count of 934 and an undetectable viral load. No alteration was found in physical examination. The patient had a good performance status and no alteration in laboratory exams.

Maternal and health care workers\u2019 perspectives on exclusive breastfeeding in the context of maternal HIV infection, in Busia county, western Kenya: a mixed methods cross-sectional survey

BackgroundWorld Health Organization recommends exclusive breastfeeding (EBF) for 6 months with maternal active antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT) of HIV. However, EBF in low resource settings remains low. We explored perspectives of EBF by HIV-infected mothers and health care workers in Busia County with a high prevalence of HIV to understand factors influencing the practice.MethodsA mixed methods cross-sectional survey using concurrent quantitative and qualitative data collection methods was conducted at PMTCT clinics. Data on socio-demography, young infant feeding practices, maternal and infant health was collected between February 2013 and August 2015 from 371 purposively sampled HIV-infected mother-infant dyads using a semi-structured questionnaire. Focus group discussions with mothers, in-depth interviews and passive observation of health care workers during interaction with mothers were conducted. Significance of difference between mothers practicing EBF or not was tested by Chi-square and Fisher’s exact tests setting significance level at 5%. Qualitative data was coded and content analyzed to generate themes.ResultsThree hundred and forty-nine (94%) mothers practiced EBF. Maternal comprehension of EBF to PMTCT of HIV influenced choice and practice of EBF (P value = 0.019 and < 0.001 respectively). Health care workers emphasized adherence to ART and offered nutritional supplementation during EBF. Health care workers’ nutritional counseling in the context of maternal HIV was poor. Mentor mothers shared their experiences with mothers and offered live case demonstrations of their successfully EBF, healthy and HIV-uninfected children. The main threats to EBF were teenage motherhood, low maternal education and working during EBF.ConclusionsEBF among HIV-infected mothers in Busia County, Kenya was high. Health education and counselling by health care workers, maternal comprehension of ART adherence to PMTCT of HIV, nutritional supplementation and mentor mothers’ peer counseling using live case demonstrations of HIV-uninfected EBF children promoted and sustained practice of EBF for 6 months. Teenage motherhood, low maternal education and having to work threatened EBF,

Dolutegravir plus lamivudine versus efavirenz\xa0plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection

BackgroundConcerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China.MethodsThis prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm.ResultsBetween September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05).ConclusionsDTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients.Clinical Trial Registration ChiCTR1900027640 (22/November/2019).