The risk of dyslipidemia on PLHIV associated with different antiretroviral regimens in Huzhou.

BACKGROUND: Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia. METHOD: PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia. RESULT: The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28-3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50-3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10-3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF. CONCLUSION: The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease.

Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial.

BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per µL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING: ANRS MIE.

Comparison of safety and effectiveness of antiretroviral therapy regimens among pregnant women living with HIV at preconception or during pregnancy: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. RESULTS: We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). CONCLUSIONS: Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

BACKGROUND: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. METHODS: The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. RESULTS: A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. CONCLUSIONS: In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.

BACKGROUND: WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited. METHODS: We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg. RESULTS: Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (p = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2). CONCLUSION: Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.

Risk Factors Of Anaemia Among Zidovudine-Based Regimen In Patients With Hiv Infection- A Cohort Study.

BACKGROUND: Anaemia in patients with HIV infection is commonly multifactorial in origin. Nutritional deficiencies and the presence of opportunistic infections as well as HIV infection itself can cause anaemia. HIV medications like zidovudine can also cause anaemia in patients with HIV infection. This study aimed to study the prevalence and risk factors of anaemia in patients with HIV infection on a zidovudine-based HAART regimen. METHODS: This hospital-based prospective cohort study was done at the ART (anti-retroviral therapy) centre. All adult patients with HIV attending the ART centre were included in the study. After obtaining written informed consent, the patient's demographic data, risk factors, WHO staging, and body mass index (BMI) were noted. Study population was divided into two groups as patients with or without anaemia and compared using appropriate statistical tests. RESULTS: Out of the 202 patients with HIV infection on a zidovudine-based regimen, 52 patients (25.7%) developed anaemia. Anaemia was common in stage 3 or stage 4 of WHO staging (OR-9.94, CI-3.89-25.36) and in patients with low CD4 counts (OR-0.988, CI-0. 982-0.995). Patients with anaemia had significant opportunistic infections. CONCLUSIONS: Anaemia is common in patients with HIV on zidovudine-based HAART regimen, which is seen as early as less than 8 weeks. WHO staging, and CD4 count were the primary risk factors for anaemia, which a change of treatment regimen and supportive measures can reverse.

REVERSIBILITY OF LIPOATROPHY IN HIV-INFECTED PATIENTS TAKING ANTIRETROVIRAL THERAPY: A COHORT STUDY WITH ULTRASOUND ASSESSMENT.

The aim of this study was to characterize and compare changes in subcutaneous fat in the malar, brachial and crural region in a cohort of HIV-infected patients taking antiretroviral therapy. This prospective longitudinal study included 77 patients who were selected from the initial cohort evaluated in 2007 and 2008. We examined reversibility of lipoatrophy measured by ultrasound over at least five-year period and factors related to its reversibility. All 46 patients who used stavudine switched from stavudine to another combination. Of 58 patients on zidovudine, 16 (28%) were on a zidovudine based regimen at the second follow up. There was evidence for subcutaneous fat increase in the malar area (p<0.001) and no increase in the brachial and crural areas. Patients who were smokers and had poor adherence to the Mediterranean diet had a thinner malar area at the follow up measurement (p=0.030) and smaller increase in subcutaneous malar fat compared to others (p=0.040). Our study suggested that modest increase of subcutaneous fat in malar area coincided with stopping stavudine and fewer usage of zidovudine. Lifestyle with non-adherence to the Mediterranean diet and smoking were associated with a smaller increase in subcutaneous malar fat.

Progression of non-anemic macrocytosis to anemia in HIV-positive persons receiving zidovudine-containing regimens in a resource-limited setting.

BACKGROUND: Non-anemic macrocytosis is frequently observed among HIV-positive persons treated with zidovudine in resource-limited settings. Although zidovudine-associated anemia is well recognized, the probability and predictors of progression from non-anemic macrocytosis to anemia are still unknown. METHODS: A retrospective cohort study was conducted among HIV-positive persons receiving zidovudine-containing antiretroviral therapy (ART) with non-anemic macrocytosis. Kaplan-Meier and Cox regression analyses were used to determine the probability and predictive factors of progression from non-anemic macrocytosis to anemia, respectively. RESULTS: Of 318 HIV-positive persons, 59.4% were male; mean age was 44.3 years. The median follow-up duration was 5.8 years. The probabilities of progression to anemia at 1, 3 and 4 years were estimated at 9.4, 17.3 and 21.3%, respectively. Almost all anemia was mild asymptomatic. Duration of zidovudine use [hazard ratio (HR) = 1.141; 95% confidence interval (CI),1.036-1.256; p = .007], CD4 count prior to start zidovudine [HR = 0.991; 95%CI,0.982-0.999; p = .038], and hematocrit level at development of macrocytosis [HR = 0.683; 95%CI,0.541-0.861; p = .001] were significant factors to predict progression to anemia. CONCLUSION: Non-anemic macrocytosis in HIV-positive persons receiving zidovudine-containing ART can progress to anemia. Longer duration of zidovudine use, lower CD4 cell counts at ART initiation, and lower hematocrit level at development of macrocytosis are predictive factors for progression to anemia.

Risk factors of severe hepatotoxicity among HIV-1 infected individuals initiated on highly active antiretroviral therapy in the Northwest Region of Cameroon.

BACKGROUND: Hepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation. METHODS: A total of 100 drug-naive patients aged between 18 and 61 years were recruited. They were put on Tenofovir/Lamivudine/Efavirenz [TDF/3TC/EFV] (64), Zidovudine/ Lamivudine/Efavirenz [AZT/3TC/EFV] (22), and Zidovudine/Lamivudine/Nevirapine AZT/3TC/NVP (14) and monitored for 6months and blood samples drawn.Alanine aminotransferases (ALT), aspartate aminotransferases (AST), and alkaline phosphatase (ALP) wereanalyzed by enzymatic methods and used to classify levels of hepatotoxicity. RESULTS: A total of 37(37%) and 49(49%) patients presented with hepatotoxicity while 15% and 28% had severe hepatotoxicity at 4 and 24 weeks respectively. Serum levels of all enzymes increased significantly (p = 0.001) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly greater in patients < 30years (p = 0.02), males(p = 0.04), low BMI (p = 0.02), low monthly income (p = 0.01) earners, and patients on AZT + 3TC + NVP regimen (p = 0.01). While multivariate analysis at p < 0.09 showed that age 30-40 years, low BMI, low monthly income, and the use of AZT + 3TC + NVP regimen were independent risk factors. CONCLUSIONS: Low BMI, age group of 30-40years, low monthly income, and the use of AZT + 3TC + NVP regimen identified as risk factors for the development of severe hepatotoxicity should be considered as an important strategy by clinicians in preventing the hepatotoxicity.

Adverse perinatal outcomes associated with HAART and monotherapy.

OBJECTIVES: Assess adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving HAART or zidovudine (ZDV) monotherapy, compared with antiretroviral therapy (ART)-naive WLHIV and HIV-negative women. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between 1 January 1980 and 20 April 2020. We included studies reporting on the association of pregnant WLHIV receiving HAART or ZDV monotherapy with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB (sPTB), low birth weight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted. RESULTS: Sixty-one cohort studies assessing 409 781 pregnant women were included. WLHIV receiving ZDV monotherapy were associated with a decreased risk of PTB [relative risk 0.70, 95% confidence interval (CI) 0.62-0.79] and LBW (0.77, 0.67-0.88), and comparable risk of SGA, compared with ART-naive WLHIV. WLHIV receiving ZDV monotherapy had a comparable risk of PTB and LBW, and an increased risk of SGA (1.16, 1.04-1.30) compared with HIV-negative women. In contrast, WLHIV receiving HAART were associated with a comparable risk of PTB and LBW, and increased risk of SGA (1.38, 1.09-1.75), compared with ART-naive WLHIV. WLHIV receiving HAART were associated with an increased risk of PTB (1.55, 1.38-1.74), sPTB (2.09, 1.48-2.96), LBW (1.79, 1.51-2.13), term LBW (1.88, 1.23-2.85), SGA (1.80,1.34-2.40), and VSGA (1.22, 1.10-1.34) compared with HIV-negative women. CONCLUSION: Pregnant WLHIV receiving HAART have an increased risk of a wide range of perinatal outcomes compared with HIV-negative women.

Zidovudine inhibits telomere elongation, increases the transposable element LINE-1 copy number and compromises mouse embryo development.

PURPOSE: Millions of pregnant, HIV-infected women take reverse transcriptase inhibitors, such as zidovudine (azidothymidine or AZT), during pregnancy. Reverse transcription plays important roles in early development, including regulation of telomere length (TL) and activity of transposable elements (TE). So we evaluated the effects of AZT on embryo development, TL, and copy number of an active TE, Long Interspersed Nuclear Element 1 (LINE-1), during early development in a murine model. DESIGN: Experimental study. METHODS: In vivo fertilized mouse zygotes from B6C3F1/B6D2F1 mice were cultured for 48 h in KSOM with no AZT (n = 45), AZT 1 µM (n = 46) or AZT 10 µM (n = 48). TL was measured by single-cell quantitative PCR (SC-pqPCR) and LINE-1 copy number by qPCR. The percentage of morulas at 48 h, TL and LINE-1 copy number were compared among groups. RESULTS: Exposure to AZT 1 µM or 10 µM significantly impairs early embryo development. TL elongates from oocyte to control embryos. TL in AZT 1 µM embryos is shorter than in control embryos. LINE-1 copy number is significantly lower in oocytes than control embryos. AZT 1 µM increases LINE-1 copy number compared to oocytes controls, and AZT 10 µM embryos. CONCLUSION: AZT at concentrations approaching those used to prevent perinatal HIV transmission compromises mouse embryo development, prevents telomere elongation and increases LINE-1 copy number after 48 h treatment. The impact of these effects on the trajectory of aging of children exposed to AZT early during development deserves further investigation.

Magnitude and associated factors of anemia among AZT based HAART experienced adult HIV patients at University of Gondar Comprehensive Specialized Referral Hospital, Northwest, Ethiopia, 2019: a retrospective cohort study.

BACKGROUND: Anemia is the most common hematologic abnormalities in AIDS patients usually associated with disease progression and poor clinical outcomes. Zidovudine (AZT), which is one of the nucleoside reverse transcriptase inhibitor drug families of the first line antiretroviral therapy regimen for HIV/AIDS patients, causes anemia due to early long-term of higher-dose therapy. This study was aimed to assess the magnitude and associated factors of anemia among AZT containing HAART experienced adult HIV/ADIS patients at University of Gondar Comprehensive Specialized Referral Hospital, northwest, Ethiopia, 2019. METHODS: A retrospective cohort study was conducted among a total of 320 adult AZT based HAART experienced HIV/AIDS patients from January 2016 to December 2018. Systematic random sampling technique was used to select the patients' charts. All required data for this study were extracted from patients' medical charts. Data were coded, cleared and entered into Epi Info version 3.5.3, and transformed to SPSS version 20 for analysis. Descriptive statistics, bivariable and multivariable logistic regression models were fitted to identify associated factors of anemia and P-value < 0.05 was considered as statistically significance. RESULTS: A total of 320 adult AZT based HAART experienced HIV/AIDS patients' charts were assessed. Of the total patients, 198 (61.9%) were females and 133 (41.6%) were within the age range of 35-45 years. More than half, 237(76.9%) of the patients were from the urban area and 186 (58.1%) were on WHO clinical stage III at the baseline. The prevalence of anemia was 50% (95% CI 44.7-55.0%), 44.1% (95% CI 38.4-50.0%), 35.6% (95% CI 30.3-40.6%), 40% (95% CI 34.4-45.6%), 40.6% (95% CI 35.0-46.3) and 39.1% (95% CI 33.4-44.1%) at baseline, 6 months, 12 months, 18 months, 24 months and 30 months of follow-up period, respectively. The overall prevalence of anemia was 41.6%. Anemia had significant association with WHO clinical stage and base line Hgb values. CONCLUSIONS: A significant number of participants were anemic in this study. WHO clinical stage and baseline Hgb value were the contributing factors for anemia among these patients. Therefore, anemia needs an immediate intervention on associated factor to improve the anemic status and living condition of HIV patient.

Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa.

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.

Adverse Reactions to Antiretrovirals in Cuban Patients Living with HIV/AIDS.

INTRODUCTION: Disease and deaths from HIV/AIDS have decreased since antiretroviral treatment was introduced in 1996. Since 2005, as treatment availability has increased worldwide, deaths from HIV/AIDS have declined 48%. As of November 2019, 26,952 cases have been reported in Cuba, of which 5159 (19.1%) are deceased. The country has experienced a reduction in mortality rates since 2002, when antiretroviral treatment became available. Although there are clearly benefits to treatment, it is important to understand antiretroviral safety profiles as their toxicity may lower treatment adherence. OBJECTIVE: Describe adverse reactions attributable to antiretrovirals used in Cuban patients living with HIV/AIDS. METHODS: I studied notifications of adverse reactions to antiretrovirals used in Cuban patients with HIV/AIDS from January 2003 to December 2017. The sample consisted of 352 notifications in the National Pharmacovigilance Database regarding adverse reactions attributed to antiretrovirals. The variables considered were sex, notification year, antiretroviral drug, and number, type, frequency and severity of adverse reactions, whether or not they were preventable, and the reasons for categorizing them as they were. RESULTS: Antiretrovirals reported an average adverse reaction rate of 2.1 per million population per year, representing 24.2% of adverse reactions produced by the antiviral drug group in that period. Adult males represented 75% (264/352) of patients who had adverse reactions to antiretrovirals. Most adverse reactions were in response to nevirapine (29.0%; 102/352) and zidovudine (26.7%; 94/352). The most frequent reactions were hypersensitivity (24.4%; 86/352), digestive disorders (15.9%; 56/352) and anemia (15.6%; 55/352). Reactions were common (62.5%; 220/352) and moderate in severity (70.4%; 248/352). Preventable reactions made up 52.6% (185/352) of adverse reactions. Of preventable reactions, 68.1% (126/185) were associated with drug interactions and 16.2% (30/185) with improper dosage or prescription errors. CONCLUSIONS: Adverse reactions to antiretrovirals in Cuban patients are common and moderate in severity. The drug with the most notifications was nevirapine, and the most common adverse reaction was hypersensitivity. More than half of adverse reactions are considered preventable, and their main causes are prescription errors.

Influence of maternal use of tenofovir disoproxil fumarate or zidovudine in Vietnamese pregnant women with HIV on infant growth, renal function, and bone health.

Tenofovir disoproxil fumarate (TDF) is still widely prescribed for human immunodeficiency virus (HIV)-infected pregnant women, despite its renal and bone toxicity. Although TDF-exposed infants often show transient growth impairment, it is not clear whether maternal TDF causes infantile rickets via maternal/fetal renal dysfunction in Asian populations. This prospective observational study was conducted in Vietnam and involved pregnant HIV-infected women treated with TDF-based regimen (TDF group) or zidovudine-based regimen (AZT-group). At birth, 3, 12, and 18 months of age, and included body length, weight, head circumference, serum alkaline phosphatase (ALP), creatinine, calcium, phosphorus, urine-ß2-microglobulin (U-BMG), percentage of tubular reabsorption of phosphate (%TRP), and radiographic wrist score for rickets. Age-adjusted multivariate linear regression analysis evaluated the association of TDF/AZT use during pregnancy with fetal renal function and bone health. The study included 63 mother-infant pairs (TDF group = 53, AZT group = 10). In the mothers, detectable U-BMG (>252 µg/L) was observed more frequently in the TDF- than AZT group (89 vs 50%, p<0.001), but other renal/bone parameters were similar. In infants, maternal TDF use was not associated with growth impairment, renal dysfunction, or abnormal bone findings, but with a slightly higher ALP levels (p = 0.019). However, shorter length was associated with maternal AZT (p = 0.021), and worse radiographic scores were associated with LPV/r (p = 0.024). In Vietnamese population, TDF usage during pregnancy was not associated with infant transient rickets, growth impairment, or renal dysfunction, despite mild maternal tubular impairment. Maternal AZT and LPV/r influenced infant growth and bone health, though further studies are needed to confirm this finding.

In-utero exposure to zidovudine-containing antiretroviral therapy and clonal hematopoiesis in HIV-exposed uninfected newborns.

OBJECTIVE: Zidovudine (ZDV) has been extensively used in pregnant women to prevent vertical transmission of HIV but few studies have evaluated potential mutagenic effects of ZDV during fetal development. DESIGN: Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were ZDV-exposed and 91 antiretroviral therapy (ART)-unexposed and matched for potential confounding factors. METHODS: Utilizing high depth sequencing and genotyping arrays, we comprehensively examined blood samples collected during the first week after birth for potential clonal hematopoiesis associated with fetal ZDV exposure, including clonal single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural copy number or copy neutral alterations. RESULTS: We observed no statistically significant difference in the number of SNVs and indels per person in ZDV-exposed children (adjusted ratio [95% confidence interval, CI] for expected number of mutations = 0.79 [0.50--1.22], P = 0.3), and no difference in the number of large structural alterations. Mutations in common clonal hematopoiesis driver genes were not found in the study population. Mutational signature analyses on SNVs detected no novel signatures unique to the ZDV-exposed children and the mutational profiles were similar between the two groups. CONCLUSION: Our results suggest that clonal hematopoiesis at levels detectable in our study is not strongly influenced by in-utero ZDV exposure; however, additional follow-up studies are needed to further evaluate the safety and potential long-term impacts of in-utero ZDV exposure in HEU children as well as better investigate genomic aberrations occurring late in pregnancy.

The association between HIV tri-therapy with the development of Type-2 Diabetes Mellitus in a rural South African District: A case-control study.

BACKGROUND: Combination antiretroviral drugs (cARVs) prolong patients' lives but are unfortunately thought to increase complications related to metabolic disorders including type-2 Diabetes Mellitus (DM). We sought to confirm the association of cARVs with type-2 DM and ascertain the extent of this association in a rural South African setting. METHODS: A case-control study of 177 (33.33%) cases with HIV/AIDS and type-2 DM were selected and compared with 354 (66.67%) non-DM HIV/AIDS unmatched controls from a rural district of South Africa's third most populous province (Eastern Cape). Cases were identified from community health centres using the district health information system, and controls were identified using simple random sampling from the same health facilities. Odds Ratios (OR), together with 95% confidence intervals, were calculated for all the univariable and multivariable logistic analyses. RESULTS: This study found that cARVs significantly increased the occurrence of type-2 DM among HIV patients. Patients on protease inhibitors (PIs) were at least 21 times significantly (p<0.0001) more likely to be diabetic than those on the fixed dose combination (FDC); those on stavudine (D4T) and zidovudine (AZT) were 2.45 times and 9.44 times respectively more likely to be diabetic than those on FDC (p<0.05). The odds of diabetes increased by more than three-folds for those who had been on antiretroviral drugs for more than 6 years (p<0.005). CONCLUSION: This study has been able to establish the association between cARVs and type-2 DM. It therefore proposes consideration of the usage of AZT, D4T, lopivavir and ritonavir for the treatment of HIV. The study further proposes more prospective research to test these findings further.

Correlation between plasma glucose and hemoglobin A1c in HIV-infected individuals receiving zidovudine and non-zidovudine containing antiretroviral therapy regimens.

BACKGROUND: Hemoglobin A1c (HbA1c) has been used for the diagnosis of diabetes and glycemic monitoring. However, using HbA1c for glycemia estimation has some fallacies in anemic persons. Zidovudine (AZT) treatment is associated with anemia and/or increased mean corpuscular volume (MCV). OBJECTIVE: This study aimed to compare the correlation between HbA1c and plasma glucose in HIV-infected individuals who were receiving AZT and non-AZT containing regimens. METHODS: A cross-sectional study was conducted in 150 HIV-infected individuals. We evaluated the correlation of paired fasting plasma glucose (FPG), random plasma glucose (RPG), mean plasma glucose (MPG) and HbA1c values by using Pearson correlation. Multivariate linear regression was used to determine the associated factors of HbA1c. RESULTS: The mean age was 49.0 ± 10.5 years, and 60.0% were male. Thirteen patients (8.7%) had diabetes and 14 patients (9.3%) had anemia. There were significant correlations between HbA1c and plasma glucose (FPG, RPG, and MPG; p < 0.05, all). The correlation between HbA1c and MPG in patients receiving AZT [HbA1c = 3.18 + 0.02MPG; R2=0.44] and not receiving AZT [HbA1c = 3.76 + 0.02MPG; R2=0.43] indicated that HbA1c in patients receiving AZT was 0.58% underestimated. Multivariate linear regression analysis showed that hematocrit [ß 0.192; 95% confidence interval (CI) 0.003, 0.690; p = 0.032] and MCV [ß -0.195; 95% CI -0.326, -0.002; p = 0.047] were associated with HbA1c levels. CONCLUSIONS: HbA1c underestimates glycemia in HIV-infected individuals receiving AZT containing regimens. Factors associated with decreased HbA1c levels in HIV-infected individuals included decreased hematocrit and increased MCV. In HIV-infected individuals receiving AZT, using HbA1c for diabetes diagnosis or glycemia monitoring should be cautiously interpreted.

Increased risk of dizziness in human immunodeficiency virus-infected patients taking zidovudine and efavirenz combination: a Brazilian cohort study.

OBJECTIVES: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine. METHODS: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled. A retrospective analysis of official medical records was accomplished to collect clinical data regarding NPAE occurrence and severity. Univariate statistic and statistical model based on survival analyses were performed. KEY FINDINGS: One hundred sixty-two patients were included, of these seventy-seven (47.5%) had NPAE reported, such as dizziness (more frequent), depression and insomnia. Univariate statistical analysis demonstrated that the combined use of efavirenz with zidovudine increased the NPAE risk (OR: 2.5; P-value: 0.008), mainly dizziness risk (OR: 3.5; P-value: 0.009) and survival analysis showed that such combination is associated with dizziness occurrence faster (HR: 2.9; P-value: 0.02). CONCLUSIONS: The results may contribute to clarify the dizziness occurrence dynamics in therapy with efavirenz and zidovudine by identifying susceptibilities and assisting in the choice of combined antiretroviral therapy.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.