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1.
World J Gastroenterol ; 30(26): 3261-3263, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39086637

ABSTRACT

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.


Subject(s)
Antiviral Agents , Hepatitis B virus , Hepatitis B, Chronic , Tenofovir , Humans , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , Tenofovir/adverse effects , Hepatitis B virus/drug effects , Treatment Outcome , Virus Replication/drug effects , Adenine/analogs & derivatives , Adenine/therapeutic use , Adenine/adverse effects , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/adverse effects
2.
J Int AIDS Soc ; 27(7): e26268, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38978403

ABSTRACT

INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.


Subject(s)
Blood Pressure , HIV Infections , Hypertension , Tenofovir , Weight Gain , Humans , Male , Female , South Africa , HIV Infections/drug therapy , Adult , Middle Aged , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Weight Gain/drug effects , Hypertension/drug therapy , Blood Pressure/drug effects , Blood Pressure/physiology , Pyridones/therapeutic use , Piperazines/therapeutic use , Oxazines/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Glomerular Filtration Rate/drug effects , Alanine/therapeutic use , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects
3.
Lancet HIV ; 11(8): e508-e521, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39008999

ABSTRACT

BACKGROUND: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up. METHODS: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (ß2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide. INTERPRETATION: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities. FUNDING: Gilead Sciences.


Subject(s)
Adenine , Alanine , Anti-HIV Agents , Emtricitabine , HIV Infections , HIV-1 , Pre-Exposure Prophylaxis , Tenofovir , Humans , HIV Infections/drug therapy , HIV Infections/virology , HIV Infections/prevention & control , Male , Tenofovir/administration & dosage , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Female , Pre-Exposure Prophylaxis/methods , Emtricitabine/administration & dosage , Emtricitabine/adverse effects , Emtricitabine/therapeutic use , HIV-1/drug effects , HIV-1/genetics , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Alanine/administration & dosage , Adenine/analogs & derivatives , Adenine/administration & dosage , Adenine/adverse effects , Adenine/therapeutic use , Drug Resistance, Viral , Middle Aged , Viral Load/drug effects , Young Adult , RNA, Viral/blood , Europe/epidemiology
4.
Ann Endocrinol (Paris) ; 85(3): 255-258, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38871510

ABSTRACT

HIV infection has been controlled only since the introduction of triple therapy in 1996, combining, as antiretroviral agents, two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI). However, among the NRTIs, the thymidine analogues stavudine and zidovudine led to lipoatrophy, either generalized or associated with visceral fat hypertrophy and buffalo hump. These molecules also increased insulin resistance and the prevalence of diabetes. They were replaced by other NRTIs or non-NRTIs (NNRTIs) that were considered to be free of adipose tissue (AT) toxicity. More recently, the NRTI tenofovir disoproxyfumarate (TDF) and the NNRTI efavirenz have been associated with inhibition of fat gain but not with clear lipoatrophy. Otherwise, the use of PIs led to a phenotype of trunk fat hypertrophy associated with cardiometabolic complications. To avoid their adverse effects, PIs have recently been replaced by a new class of antiretrovirals, the integrase inhibitors (INSTIs), which are well tolerated and effective in controlling HIV. However, this class has been associated with global weight gain, which may be important and concerning for some people living with HIV (PWH). Also, in the NRTI class, TDF has often been replaced by tenofovir alafenamide (TAF) due to bone and renal toxicities, and TAF has been associated with global fat gain. The cardiometabolic consequences of INTIs and TAF are primarily related to the associated weight gain. In the global obesogenic worldwide context, PWH are gaining weight as well in relation to poor health life conditions. Taking in charge obesity uses the same strategies as those used in the general population.


Subject(s)
Adipose Tissue , HIV Infections , Humans , HIV Infections/drug therapy , Adipose Tissue/drug effects , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/therapeutic use , HIV-Associated Lipodystrophy Syndrome/chemically induced , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Tenofovir/therapeutic use , Tenofovir/adverse effects
5.
J Obstet Gynaecol ; 44(1): 2361445, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38832538

ABSTRACT

BACKGROUND: Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin. METHODS: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery. RESULTS: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively. CONCLUSIONS: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.


Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m2 for the second and third trimesters respectively. Using the Cockcroft­Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m2 for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.


Subject(s)
Creatinine , Humans , Female , Pregnancy , Reference Values , Adult , Creatinine/blood , Kidney Function Tests/methods , South Africa , Kidney/physiopathology , Young Adult , HIV Infections/drug therapy , Tenofovir/adverse effects , Anti-HIV Agents/adverse effects
6.
AIDS ; 38(9): 1442-1445, 2024 07 15.
Article in English | MEDLINE | ID: mdl-38932750

ABSTRACT

Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT.


Subject(s)
Adenine , Alanine , Anti-HIV Agents , Fanconi Syndrome , HIV Infections , Tenofovir , Humans , Tenofovir/adverse effects , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , Alanine/adverse effects , Alanine/therapeutic use , Male , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/complications , Adenine/analogs & derivatives , Adenine/adverse effects , Adenine/therapeutic use , Female , Fanconi Syndrome/chemically induced , Adult , Middle Aged
7.
PLoS One ; 19(6): e0303442, 2024.
Article in English | MEDLINE | ID: mdl-38885284

ABSTRACT

BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.


Subject(s)
Alpha-Globulins , Biomarkers , HIV Infections , Tenofovir , beta 2-Microglobulin , Humans , Male , beta 2-Microglobulin/urine , Alpha-Globulins/urine , Tenofovir/therapeutic use , Tenofovir/adverse effects , HIV Infections/drug therapy , HIV Infections/urine , HIV Infections/complications , Biomarkers/urine , Middle Aged , Adult , Retrospective Studies , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Acute Kidney Injury/urine , Acute Kidney Injury/chemically induced , Acute Kidney Injury/etiology
8.
Lancet Gastroenterol Hepatol ; 9(8): 718-733, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38901444

ABSTRACT

BACKGROUND: Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. METHODS: This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFRCG) 15-59 mL/min] or end-stage renal disease [eGFRCG <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. FINDINGS: 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR -2·8 to 4·5) in cohort 1 and -2·4 mL/min (-11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and -0·25% (3·91) and 0·28% (3·25) in part B. INTERPRETATION: Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. FUNDING: Gilead Sciences.


Subject(s)
Adenine , Alanine , Antiviral Agents , Hepatitis B, Chronic , Tenofovir , Humans , Male , Female , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Middle Aged , Alanine/therapeutic use , Alanine/adverse effects , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Adult , Adenine/analogs & derivatives , Adenine/therapeutic use , Adenine/adverse effects , Drug Substitution , Aged , Treatment Outcome , Glomerular Filtration Rate/drug effects
9.
J Med Virol ; 96(7): e29760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38940453

ABSTRACT

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.


Subject(s)
Antiviral Agents , Cardiovascular Diseases , Hepatitis B, Chronic , Tenofovir , Humans , Male , Hepatitis B, Chronic/drug therapy , Female , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Middle Aged , Adult , Republic of Korea/epidemiology , Dyslipidemias/chemically induced , Dyslipidemias/epidemiology , Cohort Studies , Guanine/analogs & derivatives , Guanine/therapeutic use , Guanine/adverse effects , Alanine
10.
Lancet HIV ; 11(6): e380-e388, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740027

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , Emtricitabine , HIV Infections , HIV-2 , Ritonavir , Tenofovir , Humans , HIV Infections/drug therapy , Adult , Male , Female , HIV-2/drug effects , Tenofovir/therapeutic use , Tenofovir/adverse effects , Pilot Projects , CD4 Lymphocyte Count , Emtricitabine/therapeutic use , Emtricitabine/administration & dosage , Emtricitabine/adverse effects , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Anti-HIV Agents/administration & dosage , Treatment Outcome , Ritonavir/therapeutic use , Ritonavir/administration & dosage , Ritonavir/adverse effects , Lopinavir/therapeutic use , Lopinavir/adverse effects , Lopinavir/administration & dosage , Raltegravir Potassium/therapeutic use , Raltegravir Potassium/adverse effects , Raltegravir Potassium/administration & dosage , Lamivudine/therapeutic use , Lamivudine/administration & dosage , Lamivudine/adverse effects , Viral Load/drug effects , Antiretroviral Therapy, Highly Active , Middle Aged , Zidovudine/therapeutic use , Zidovudine/adverse effects , Zidovudine/administration & dosage , Drug Therapy, Combination , HIV-1/drug effects
11.
Medicine (Baltimore) ; 103(20): e37953, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758884

ABSTRACT

To explore the therapeutic effectiveness of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on the treatment for chronic hepatitis B (CHB). Retrospectively analyzing 241 cases of chronic hepatitis B patients admitted to our hospital from January 2020 to December 2021, they were divided into a TAF group of 180 cases and a TDF group of 61 cases. The liver function, serum virus markers, clinical efficacy, adverse reactions and cost-effectiveness ratio (CER) analysis of 2 groups were compared. Two groups of patients had no statistically significant difference in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) before treatment. After treatment, the levels of ALT, AST and TBIL were lower than before treatment in both groups (P < .05), but the inter-group difference was not statistically significant (P > .05). After treatment, Hepatitis B surface antigen (HBsAg) conversion rate and Hepatitis B virus DNA (HBV-DNA) conversion rate in the 2 groups had no statistically significant difference. After treatment, the difference in total clinical cure rate between the 2 groups has no statistical significance (P > .05), adverse reactions rate of TAF group was lower than that of TDF group (P < .05). The drug cost median of TAF group was higher than that of TDF (P < .05), but Cost-effectiveness analysis showed the CER of TAF group was similar of TDF group. TAF or TDF therapy can both improve liver function and promote recovery in patients with CHB, achieving the goal of treatment. TAF have more cost but have similar CER to TDF. Moreover, TAF therapy has a higher safety profile.


Subject(s)
Antiviral Agents , Hepatitis B, Chronic , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Male , Female , Retrospective Studies , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Adult , Middle Aged , Treatment Outcome , Cost-Benefit Analysis , Alanine/therapeutic use , DNA, Viral/blood , Alanine Transaminase/blood , Hepatitis B Surface Antigens/blood
12.
Pak J Pharm Sci ; 37(2): 367-375, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767104

ABSTRACT

The efficacy of 400mg efavirenz (EFV) once daily is reported to be similar to that of 600mg EFV. However, EFV-related toxic and side effects of 400mg EFV are significantly reduced. Here, the feasibility of reducing EFV to 400mg once a day in HIV-infected/AIDS patients was evaluated. Fifty patients were included. Patients were given 3TC+TDF+400mg EFV (n=25) or 3TC+TDF+600mg EFV (n=25). The proportion of patients with HIV RNA < 40 copies/mL and the adverse events served as the primary and secondary outcomes, respectively. HIV inhibition rates of the 3TC+TDF+400mg EFV group and 3TC+TDF+600mg EFV group were both 56.52% at week 24 and respectively 100%, 91.3% at week 48. During 48 weeks, 27 cases of adverse events were reported in the 3TC+TDF+400mg EFV group, lower than those in the 3TC+TDF+600mg EFV group, which had 39 cases. Compared with the 3TC+TDF+400mg EFV group, the incidence of transaminase, dizziness, hyperlipidemia and rashes all increased in the 3TC+TDF+600mg EFV group (P>0.05). No serious adverse events of the central nervous system occurred. The incidence of depression, sleep disturbance, and vertigo were similar (P>0.05). The efficacy of 400mg EFV is comparable to 600mg EFV. However, patients receiving 400mg EFV have fewer adverse events.


Subject(s)
Alkynes , Anti-HIV Agents , Benzoxazines , Cyclopropanes , HIV Infections , Humans , Benzoxazines/adverse effects , Benzoxazines/administration & dosage , Benzoxazines/therapeutic use , Cyclopropanes/administration & dosage , Male , Female , Adult , Anti-HIV Agents/adverse effects , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Middle Aged , Treatment Outcome , Lamivudine/administration & dosage , Lamivudine/adverse effects , Lamivudine/therapeutic use , Tenofovir/adverse effects , Tenofovir/administration & dosage , Tenofovir/therapeutic use , Drug Therapy, Combination , Viral Load/drug effects , RNA, Viral , Acquired Immunodeficiency Syndrome/drug therapy
13.
Biosci Trends ; 18(2): 141-152, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38658364

ABSTRACT

Antiretroviral therapy (ART) has significantly enhanced the outlook for people with HIV(PWH), yet certain ART medications can adversely affect the renal function of these patients. Of particular concern is the nephrotoxicity associated with tenofovir disoproxil fumarate (TDF). Compared to TDF, tenofovir alafenamide (TAF), another prodrug of tenofovir (TFV), results in lower TFV plasma levels, thereby alleviating the TFV-associated mitochondrial toxicity on proximal renal tubular cells. Currently, numerous clinical trials and real-world studies have demonstrated the favorable renal safety profile of ART regimens incorporating TAF for PWH. This paper seeks to consolidate the available evidence regarding the renal safety of TAF-based regimens in PWH, encompassing both the general PWH and those with renal impairment or predisposing factors, in order to offer recommendations and insights for TAF clinical application.


Subject(s)
Adenine , Alanine , Anti-HIV Agents , HIV Infections , Tenofovir , Humans , Tenofovir/adverse effects , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , HIV Infections/drug therapy , Alanine/adverse effects , Alanine/therapeutic use , Alanine/analogs & derivatives , Adenine/analogs & derivatives , Adenine/adverse effects , Adenine/therapeutic use , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Kidney/drug effects
14.
Lancet HIV ; 11(5): e300-e308, 2024 May.
Article in English | MEDLINE | ID: mdl-38621393

ABSTRACT

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.


Subject(s)
Adenine , Alanine , Amides , Anti-HIV Agents , Emtricitabine , HIV Infections , Heterocyclic Compounds, 3-Ring , Heterocyclic Compounds, 4 or More Rings , Piperazines , Pyridones , Tenofovir , Tenofovir/analogs & derivatives , Humans , Emtricitabine/pharmacokinetics , Emtricitabine/administration & dosage , Emtricitabine/therapeutic use , Emtricitabine/adverse effects , HIV Infections/drug therapy , HIV Infections/virology , Tenofovir/pharmacokinetics , Tenofovir/administration & dosage , Tenofovir/adverse effects , Tenofovir/therapeutic use , Child , Male , Female , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/adverse effects , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Child, Preschool , Alanine/pharmacokinetics , Alanine/adverse effects , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Heterocyclic Compounds, 4 or More Rings/adverse effects , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Amides/pharmacokinetics , Adolescent , Pyridones/pharmacokinetics , Pyridones/adverse effects , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Piperazines/adverse effects , Piperazines/pharmacokinetics , Adenine/analogs & derivatives , Adenine/pharmacokinetics , Adenine/adverse effects , Adenine/administration & dosage , Adenine/therapeutic use , Thailand , United States , South Africa , Drug Combinations , Uganda , Viral Load/drug effects
15.
Nurs Clin North Am ; 59(2): 189-200, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38670689

ABSTRACT

Integrase inhibitors and tenofovir alafenamide have become a mainstay in modern antiretroviral therapy; more recently, they have been implicated as causing increased weight gain beyond what may be expected with the "return to health" phenomenon. Some patients, namely those assigned female at birth, of the black race, or with lower baseline CD4 counts, may be more likely to experience weight gain. This review outlines existing evidence linking the agents to excessive weight as well as ongoing efforts to combat these effects.


Subject(s)
HIV Infections , Weight Gain , Humans , HIV Infections/drug therapy , Weight Gain/drug effects , Female , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Tenofovir/therapeutic use , Tenofovir/adverse effects , Male , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects
16.
Lancet HIV ; 11(5): e321-e332, 2024 May.
Article in English | MEDLINE | ID: mdl-38621392

ABSTRACT

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.


Subject(s)
Body Mass Index , Dyslipidemias , HIV Infections , Hypertension , Tenofovir , Tenofovir/analogs & derivatives , Humans , Female , Male , HIV Infections/drug therapy , Tenofovir/adverse effects , Tenofovir/therapeutic use , Hypertension/epidemiology , Hypertension/chemically induced , Prospective Studies , Dyslipidemias/chemically induced , Dyslipidemias/epidemiology , Middle Aged , Adult , HIV Integrase Inhibitors/adverse effects , HIV Integrase Inhibitors/therapeutic use , Alanine/adverse effects , Australia/epidemiology , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Weight Gain/drug effects , Europe/epidemiology , Risk Factors , Drug Therapy, Combination/adverse effects
17.
HIV Med ; 25(7): 826-839, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38520085

ABSTRACT

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.


Subject(s)
Alkynes , Benzoxazines , Cyclopropanes , HIV Infections , Heterocyclic Compounds, 3-Ring , Oxazines , Pyridones , Weight Gain , Humans , Male , Female , Weight Gain/drug effects , HIV Infections/drug therapy , Adult , South Africa , Retrospective Studies , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Oxazines/therapeutic use , Benzoxazines/therapeutic use , Benzoxazines/adverse effects , Benzoxazines/administration & dosage , Middle Aged , Piperazines , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Longitudinal Studies , Body Mass Index , Lamivudine/therapeutic use , Lamivudine/adverse effects , Lamivudine/administration & dosage , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/administration & dosage , Emtricitabine/therapeutic use , Emtricitabine/administration & dosage
19.
Indian Pediatr ; 61(4): 337-342, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38449277

ABSTRACT

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.


Subject(s)
Anti-HIV Agents , HIV Infections , Child , Humans , Adolescent , Tenofovir/adverse effects , Creatinine/pharmacology , Creatinine/therapeutic use , Anti-HIV Agents/adverse effects , Prospective Studies , Uric Acid/pharmacology , Uric Acid/therapeutic use , HIV Infections/drug therapy , Proteinuria , Glomerular Filtration Rate , Phosphates/therapeutic use , Glucose/pharmacology , Glucose/therapeutic use
20.
J Int AIDS Soc ; 27(3): e26223, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38444118

ABSTRACT

INTRODUCTION: Tenofovir-based oral pre-exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user-controlled long-acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90-day TFV ring. METHODS: Between January and June 2019, Microbicide Trials Network (MTN)-038 enrolled 49 HIV-negative participants into a phase 1, randomized (2:1) trial comparing a 90-day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV-diphosphate (TFV-DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self-report. RESULTS: Mean age was 29.5; 46 identified as cisgender-female and three gender non-conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV-DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low (<0.1 g) residual TFV. Residual TFV did not differ by socio-demographics, sexual activity, Nugent Score or vaginal microbiota. Most participants reported being fully adherent to ring use: 85% and 81% in the TFV and placebo arms, respectively (p = 1.00). A majority of participants reported liking the ring (median 8 on a 10-point Likert scale) and reported a high likelihood of using the ring in the future, if effective (median 9). CONCLUSIONS: The 90-day TFV ring was well-tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use.


Subject(s)
HIV Infections , Tenofovir , Adult , Female , Humans , Adenine , Herpesvirus 2, Human , HIV Infections/drug therapy , HIV Infections/prevention & control , Microbiota , Tenofovir/adverse effects , Tenofovir/pharmacokinetics , United States
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