Combination Of Tenofovir Research Articles

Combined bictegravir, emtricitabine and tenofovir alafenamide for treating people with HIV: a plain language summary of the BICSTaR study up to 1year.

This is a summary of an article about an ongoing study called the BICSTaR study.The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test.People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment.Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year. Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an 'undetectable viral load' and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly.Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1year. B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects.

Impact of Dolutegravir-based Regimen on Tolerance and Virologic Suppression, Compared to Non-dolutegravir Regimen among PLHIV in Southern Senegal

Background: In 2020, Senegal began a transition to a Dolutgravir-based treatment as a first-line regimen in all new ART initiators in accordance with WHO recommendations. Aims: To determine the virological suppression and the tolerance on patients under a dolutegravir-based regimen by comparison with patients on a regimen without dolutegravir after at least 6 months of treatment. Materials and Methods: A cross-sectional study based on retrospective data (from January 2nd, 2017 to June 30th; 2022) involving 469 patients, 219 people were initiated with Dolutegravir regimen ART between Jan 2nd, 2020, and June 30th, 2022, and 250 patients treated using the old protocol (non-dolutegravir regimen). Patients who had received both the old protocol then switched to a DTG based regimen were excluded from the study. A single questionnaire was used to collect data. Sociodemographic, clinical and virological parameters and the last control of the virological load were analyzed with Stata 16 software. Descriptive statistics and univaried analysis were also carried-out. Results: In the dolutegravir regimen ART group, 161 (73, 52%) of 219 were women and 58 (26.48) were men. The median participant age was 43·0 years (IQR 33·0–53·0) and the median time on ART was 28·0 months (23·0–36·0). The dolutegravir-based regimen combined tenofovir, lamivudine and dolutegravir. 15 (6, 85 %) were receiving tuberculosis treatment at the time of ART initiation. The proportion of patients screened at an advanced clinical stage of AIDS (WHO stage 3 or 4) were 63, 47%. People initiated on dolutegravir were more likely to be retained in care at 12 months (100% vs. 95.20%; p=0.075) and having viral suppression (96.80%vs. 96.40% ; p=0,810) compared with those initiated on non-dolutegravir-based regimens but the difference was not statistically significant. Fewer patients presented side effects due to triple therapy in the dolutegravir-based regimen group compared to the non-dolutegravir group (2.74% vs. 3.20%; p=0.77). In the dolutegravir based regimen the side effects were mainly vomiting, insomnia, and dizziness. The mean gain weight was 6,7± 8,2 kilograms. For the non-dolutegravir regimen group, 195 (78.00%) were women. The median participants age was 43·0 years (IQR 34·0–53·0) and the median time on ART was 55·0 years (48·0–65·0) months. 18 (7, 20%) were receiving tuberculosis treatment at time of ART initiation. The therapeutic protocol combined TDF, lamivudine, Efavirenz in 225 cases (90%). A percentage of 59.20% patients were screened at an advanced clinical stage of AIDS (WHO Stage 3 and 4). In this group the side effects were mainly nausea and insomnia and the mean gain weight was 7,2 ± 6,2 kilograms. Conclusion: The results of our study show a high rate of viral suppression, and good tolerance of the dolutegravir-based regimen in a decentralized setting.

Prevalence of residual replication in HIV-1 patients on Tenofovir, Lamuvidine and Dolutegravir (TLD) treatment followed at Al-Nadjma Multipurpose Center from 2021 to 2023

Objective: The objective of this study is to determine the prevalence of residual replication in HIV-1-infected patients receiving TLD from 2021 to 2023 followed at the Polyvalent Al-Nadjma center. Material and method: This was a retrospective and prospective study with an analytical aim which took place at the Polyvalent Al-Nadjma center from April 2022 to December 2023 in the city of N’Djamena. The study began with the interview of 135 patients, 108 of whom signed informed consent to participate in this study. Patients infected with HIV 1 on ART based on the combination of Tenofovir, Lamivudine and Dolutegravir (TLD) for at least 2 years with a load of 999 copies/mL were included. A total of 108 plasmas were collected and analyzed by the RT-PCR technique. The data from the interviews as well as the RT-PCR results were analyzed with R Studio software. Results: the results of this study revealed a female predominance with 70% (76/108) with a M/F sex ratio of 0.42. The average age of the patients was 40.58 ± 9.58 years. The prevalence of persistent residual replication was 22.22% (n = 24/108), 54.60% (n = 59/108) of patients had virological success, and 19.44% (n = 21/108) of patients had a viral load greater than or equal to 1000 copies/mL and 3.70% (n = 4/108) had an invalid plasma viral load. Conclusion: The aim of this work was to determine the prevalence of residual replication in patients infected with HIV-1 under Tenofovir, Lamuvidine and Dolutegravir (TLD) followed at the Al-Nadjima/APMS multipurpose center in N’Djamena, Chad. The prevalence of residual replication in this study was 22.22%. This study demonstrated that individuals with a persistent viral load below 1000 copies/mL were at increased risk of therapeutic and virological failure due to the lack of consensus and failure to control the phenomenon of residual replication in patients infected with HIV-1 under TLD

HIV viral suppression at different thresholds and duration of treatment in the dolutegravir treatment era in Sierra Leone: a nationwide survey

IntroductionViral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone.MethodsWe used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P < 0.05.ResultsOf the 2,253 patients recruited, 1,720 (76%) were women and 1,705 (76%) were receiving a fixed dose combination of tenofovir, lamivudine and dolutegravir. The median age and duration of anti-retroviral therapy (ART) was 36.0 (IQR, 28.0–45.0) years and 40.9 (IQR, 14.4–79.6) months, respectively. Using a threshold of HIV RNA < 1000 copies/mL, 1,715 (88.4%) patients on ART for more than 6 months were virally suppressed. Viral suppression rates were higher with dolutegravir-based (1,277, 89.5%) than efavirenz-based (418, 86.2%) ART. HIV RNA was < 200 copies/mL in 1,643 (84.6%) patients or < 50 copies/mL in 1,487 (76.6%) patients or between 50 and 999 copies/mL in 228 (11.7%) patients. Viral suppression rates at different ART durations (months) were as follows: 84.2% (≤ 3), 88.8% (4–6), 90.9% (6–12), and 88.1% (> 12). Viral suppression rates were higher for patients aged 40 or older (40–50 years: aOR 2.05, 95%CI 1.41–3.04, P < 0.01; 50–60 years: aOR 2.51, 95%CI 1.53–4.35, P < 0.01; >60 years: aOR 2.69, 95%CI 1.28–6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38–0.67, P < 0.01).ConclusionWe report a viral suppression rate of 88.4% among patients on treatment for at least 6 months, with higher rate of suppression with dolutegravir than efavirenz. Factors associated with virological suppression were age and gender, emphasizing the need for innovative differentiated ART delivery models to optimize viral suppression and achieve the 95% target.

The Effect of Antiretroviral Therapy (ART) Duration on CD4 Counts in Human Immunodeficiency Virus (HIV) Patients in dr. Doris Sylvanus Regional Hospital

Human Immunodeficiency Virus (HIV) attacks white blood cells, thereby reducing the immunity of infected patients. It attacks Cluster of Differentiation 4 (CD4) lymphocyte cells which have a role in the immune system. It has killed 36.3 million people worldwide. There were reported 222 cases in Central Kalimantan Province in 2019. The therapy given to suppress HIV is antiretroviral (ARV) which gradually recover CD4 cells of the patients. This study aims to determine the effect of duration of the antiretroviral therapy (ART) duration on CD4 counts in patients with HIV at the VCT (Voluntary, Counselling, and Test) Polyclinic, dr. Doris Sylvanus Hospital during 2019-2020. It is a descriptive retrospective study, extracting data from patients medical record data. Following total sampling and selected based on inclusion and exclusion criteria i.e. aged ≥18 years and diagnosed with HIV during 2019-2020, with complete CD4 count records prior and after ART, there were 45 patients included. The results showed that CD4 counts increased in patients with fixed dose combination (FDC) Tenofovir, lamivudine and efavirenz, with average value of 190.36± 220.92 cells/mm3 prior ART, became 259.93± 203.74 cells/mm3 at 12 month ART, and 310.82± 22.,53 cells/mm3 at 24 month ART (p = 0.000). Thus, the longer ART duration the higher CD4 counts and recover the normal range.

Identification of integrase inhibitor-related drug resistance mutations in newly diagnosed ART-naïve HIV patients

BackgroundIn China, the recommended treatment regimens for HIV-infected individuals were tenofovir in combination with lamivudine or emtricitabine as NRTIs, efavirenz or rilpivirine as NNRTIs, lopinavir/ritonavir as protease inhibitors, and raltegravir or dolutegravir as INSTIs. The development of drug resistance increases the risk of viral rebound, opportunistic infections, and ultimately treatment failure such that the early detection of resistance is ideal. This study was developed to explore primary drug resistance characteristics and genotypic distributions in newly diagnosed antiretroviral therapy (ART)-naïve HIV-1 patients in Nanjing with the goal of establishing a basis for their individualized treatment in the clinic. MethodsSamples of serum were collected from newly diagnosed ART-naïve HIV patients from the Second Hospital of Nanjing between May 2021 and May 2022. The HIV-1 integrase (IN), protease (PR), and reverse transcriptase (RT) gene coding sequences were amplified from these samples, sequenced, and assessed for drug resistance-related mutations. ResultsMajor integrase resistance-related mutations were detected in 4/360 amplified samples, with 5 other patient samples exhibiting accessory resistance mutations. The overall prevalence of PR and RT inhibitor-related transmitted drug resistance mutations (TDRMs) in this patient population was 16.99% (61/359). The most common mutations were non-nucleoside reverse transcriptase inhibitor-related mutations (51/359; 14.21%), followed by those associated with nucleoside reverse transcriptase inhibitors (7/359; 1.95%) and protease inhibitors (7/359; 1.95%). Dual-resistant strains were also observed in a subset of patients. ConclusionsIn summary, this study is the first to have surveyed the prevalence of integrase inhibitor resistance-related mutations and other drug resistance-related mutations among newly diagnosed ART-naïve HIV-positive patients in Nanjing, China. These results highlight the need for further molecular surveillance-based monitoring of the HIV epidemic in Nanjing.

Dolutegravir-associated resistance mutations after first-line treatment failure in Brazil

BackgroundSince January 2017, the recommended first-line antiretroviral regimen in Brazil is the fixed-dose combination of tenofovir plus lamivudine with dolutegravir (TL + D). According to the literature, integrase resistance-associated mutations (INRAMs) are rarely found upon virologic failure to first-line dolutegravir plus two nucleoside reverse transcriptase inhibitors. We evaluated the HIV antiretroviral genotypic resistance profile of patients referred for genotyping in the public health system who failed first-line TL + D after at least six months of therapy on or before December 31, 2018.MethodsHIV Sanger sequences of the pol gene were generated from plasma of patients with confirmed virologic failure to first-line TL + D in the Brazilian public health system before December 31, 2018.ResultsOne hundred thirteen individuals were included in the analysis. Major INRAMs were detected in seven patients (6.19%), four with R263K, one with G118R, one with E138A, and one with G140R. Four patients with major INRAMs also had the K70E and M184V mutations in the RT gene. Sixteen (14.2%) additional individuals presented minor INRAMs, and five (4,42%) patients had both major and minor INRAMS. Thirteen (11.5%) patients also presented mutations in the RT gene selected by tenofovir and lamivudine, including four with both the K70E and M184V mutations and four with only M184V. The integrase mutations L101I and T124A, which are in the in vitro pathway for integrase inhibitor resistance, were found in 48 and 19 patients, respectively. Mutations not related to TL + D, thus probable transmitted resistance mutations (TDR), were present in 28 patients (24.8%): 25 (22.1%) to nucleoside reverse transcriptase inhibitors, 19 (16.8%) to non-nucleoside reverse transcriptase inhibitors, and 6 (5.31%) to protease inhibitors.ConclusionsIn marked contrast to previous reports, we report a relatively high frequency of INRAMs among selected patients failing first-line TL + D in the public health system in Brazil. Possible reasons for this discrepancy include delays in detecting virologic failure, patients inadvertently on dolutegravir monotherapy, TDR, and/or infecting subtype.

Comparison of the long-term efficacy of Tenofovir monotherapy versus Tenofovir and Phyllanthus Amari combination therapy: a randomized controlled trial

Hepatitis B infection has become a social burden in over the world due to its high prevalence, while the treatments still do not offer the desired effects. Literature showed that combining traditional medicine with modern drugs was able to inhibit the proliferation of the hepatitis B virus, thus making it an effective treatment. To compare the efficacy of Tenofovir monotherapy versus Tenofovir and Phyllanthus Amari combination therapy in chronic hepatitis B patients. Randomized controlled clinical trial on 200 chronic hepatitis B patients with HBeAg (+); divided into 2 groups: The combination therapy group used Phyllanthus Amari product and Tenofovir for treatment and the monotherapy group with Tenofovir. The serological, biological, and virological responses in the combination therapy group were earlier than those in the monotherapy group. Statistically significant differences in serological responses between the combination therapy versus monotherapy group were achieved from the 3rd (59% versus 33%, p=0.021) to the 18th month (99% versus 91%, p=0.029). Statistically significant differences in biochemical responses between the combination therapy versus monotherapy group were achieved from the 9th (12% versus 1%, p=0.003) to the 18th month (35% versus 21%, p=0.040). Statistically significant differences in virological response between the combination therapy versus monotherapy group were achieved from the 6th (23% versus 10%, p=0.021) to the 18th month (97% versus 88%, p=0.029). The combination of Tenofovir and the Phyllanthus Amari product is more effective than using only Tenofovir for treatment in chronic hepatitis B patients with HBeAg-positive.

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

Identification of HIV-1 subtype CRF18_cpx in a patient with multidrug resistance in KwaZulu-Natal, South Africa: An epidemiological worry?

The most common HIV-1 subtype in South Africa is subtype C, and detection of other subtypes is rare. We report the first known case of HIV-1 subtype CRF18_cpx identified in KwaZulu-Natal, South Africa, the epicenter of the HIV epidemic, through HIV drug resistance genotyping.The 31-year-old female patient was initiated on fixed dose combination (tenofovir, emtricitabine, efavirenz) in 2017, with failure to achieve virologic suppression. Change to second-line antiretroviral therapy (tenofovir, emtricitabine and ritonavir-boosted lopinavir) was made in 2018. Adherence was impacted by lopinavir-induced diarrhoea. In 2020, she was switched to zidovudine, lamivudine and ritonavir-boosted atazanavir. Virologic failure persisted, and HIV drug resistance genotyping in April 2021 showed multidrug resistance. Third-line regimen (tenofovir, lamivudine, dolutegravir and ritonavir-boosted darunavir) was commenced in May 2021 and virologic suppression was achieved.Co-incidentally we discovered from the HIV drug resistance sequence report that the patient was infected with HIV-1 subtype CRF18_cpx. Analysis of the HIV sequence using REGA HIV-1 Subtyping Tool confirmed sequence subtype assignment as HIV-1 CRF 18_cpx (bootstrap confidence = 90%). Subtyping was also confirmed with the COMET HIV-1 tool, HIV BLAST tool and phylogenetic analysis.Based on our incidental finding, CRF18_cpx may be circulating locally as the patient had no travel history. Introduction of non-subtype C and recombinant viruses are expected to have increased in South Africa due to increased travel. This highlights the need to characterize subtype diversity in South Africa, particularly in KwaZulu-Natal, as HIV subtype can influence pathogenesis, treatment response, drug resistance and efforts towards vaccine development.

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

BackgroundThe adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART.ResultsTNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs.ConclusionsWe show that the combination of TNF and AuNPs exhibits multifunctional activity, viz. anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS.Graphical

Efficacy, Tolerability, and Compliance of Direct Acting Antivirals in Patients with HIV and Hepatitis C Coinfection: A Real-Life Experience.

Effective management of HIV and hepatitis C virus (HCV) coinfection warrants special emphasis on interactions between direct acting antivirals (DAAs) and antiretroviral therapy (ART) along with maintenance of treatment compliance. All HIV-HCV coinfected adult patients (2015-2020) were included in this real-life retrospective study. Prevalence of coinfection, proportion of coinfected patients treated, compliance rate, sustained virological response at week 12 (SVR12) after the end of therapy, and adverse events were assessed. Among 4578 HIV patients, 232 (5.1%) had HCV coinfection. Ninety-two (39.7%) were intravenous drug users. One hundred twenty-eight (55.1%) patients presented to the liver clinic. Seventy-six (32.8%) patients [mean age: 36.6 ± 10.4 years; 65 (85.5%) males; mean CD4 count: 396 ± 246 cells/mL] completed DAA therapy, whereas 52 (22.4%) patients defaulted and 75 (32.3%) were lost to follow-up. Sixty-seven (82.2%) patients had chronic hepatitis and 9 (11.8%) had compensated cirrhosis. Median (range) HCV-RNA was 5.9 × 106 IU/mL (2.4 × 105-9.9 × 105). Among 15 (19.5%) treatment experienced patients, 14 were pegylated interferon experienced and one was NS5A-inhibitor experienced. ART regimens comprised a combination of tenofovir (T), lamivudine (L), efavirenz (E), nevirapine (N), and/or zidovudine (Z) at dosage and modifications as applicable [TLE: 63 (82.9%), ZLN:11 (14.5%), and ZLE: 2 (2.6%)]. Overall, 74 (97.4%) out of 76 patients who completed DAA therapy achieved SVR12. Adverse events were minor and well-tolerated. HIV-HCV-coinfected patients demonstrate excellent SVR12 and tolerability with available DAAs, with no major adverse events.

Tenofovir use is associated with a decreased risk of hepatocellular carcinoma among men with HIV irrespective of coinfection status

Tenofovir is recommended as part of the first-line antiretroviral therapy (ART) to treat people living with HIV (PLWH) with HBV coinfection. However, the effects of tenofovir-containing ART on hepatocellular carcinoma (HCC) risk among PLWH with/without chronic hepatitis virus infections remain unclear. This study included 23,838 PLWH. All of them were males aged ≥20 years and followed prospectively during 2000-2017. Four major nationwide registries - the Human Immunodeficiency Virus surveillance database, Taiwan Cancer Registry, Death Certification System, and National Health Insurance Database - were applied to define ART and comorbidities and ascertain newly diagnosed HCC. Tenofovir-containing ART was identified through prescription records. Cox proportional hazards models were used to determine the association of tenofovir use with HCC incidence. HCC incidence was lower among ever users of tenofovir than among never users (24.2 and 85.7 per 100,000 person-years, respectively). Ever users had significantly reduced HCC risk (adjusted hazard ratio 0.20, 95% CI 0.13-0.31). The effect of tenofovir use on reduced risk for HCC consistently favored never users across many prespecified subgroups, including HBV or HCV coinfection (p <0.05). The findings were consistent in subgroups of PLWH diagnosed with HIV before tenofovir's approval and in those born before the nationwide roll-out of neonatal HBV vaccination. Our findings underscore the need for randomized controlled trials of tenofovir in combination with long-acting injectable ART regimens to assess its safety and efficacy in PLWH, particularly in those with HBV or HCV coinfection. Tenofovir's effect on the risk of hepatocellular carcinoma (HCC) among people living with HIV with hepatitis B or C coinfection remains under investigated. This nationwide prospective cohort study, comprising 23,838 men living with HIV, showed that tenofovir-containing antiretroviral therapy was associated with reduced risk of HCC (adjusted relative risk: 0.20, 95% CI 0.13-0.31), which was consistently observed across many prespecified subgroups. The effect of tenofovir use on HCC risk should be further investigated in PLWH, particularly following the development of long-acting injectable ART regimens.

The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with human immunodeficiency virus.

The factors responsible for this reported fertility decline among human immunodeficiency virus (HIV) positive men is yet to be determined. This study is aimed at investigating the impact of HIV or combination antiretroviral therapy (cART) on sperm cells, reproductive hormones, oxidative stress markers, apoptosis, and sperm DNA fragmentation of men living with HIV. Twenty-one men living with HIV gave their written informed consent to participate in this study. Only 11 of the participants successfully donated blood and semen before and after 3 months of their treatment with cART. Semen, reproductive hormones, oxidative stress biomarkers, and DNA fragmentation were analysed. Data were subjected to Wilcoxon matched pairs signed rank test (ethical approval: CMUL/HREC/09/19/614). There was a significant decrease in viral load of HIV (p < 0.01), and a marked increase in progressive and total sperm motility. Total sperm count, morphology, and vitality had no significant change after 3 months of treatment with cART however, there was a significant increase (p < 0.05) in testosterone from 2.48 to 3.68 ng/ml, but luteinizing hormone decreased significantly (p < 0.05) from 9.6 to 6.5mIU/ml. In addition, sperm DNA fragmentation increased significantly (p < 0.01). Conversely, viral load, and catalase decreased significantly, but no significant difference in malondialdehyde. This study showed that HIV depleted testosterone and impaired sperm motility which may negatively affect the fertility potential of men living with HIV. It also showed that adherence to cART (a combination of tenofovir, lamivudine, and dolutegravir) reduces the viral load and reverses the deleterious effects of cART albeit, cART appears to be toxic at subcellular spermatogenic levels.

Bulevirtide and tenofovir combination therapy for hepatitis D virus infection: longer treatment and more diverse trial populations are needed

Hepatitis D virus (HDV) is a defective RNA virus requiring hepatitis B virus (HBV) to complete its lifecycle.1 HDV viruses have been classified into eight genotypes on the basis of their genome diversity, with specific geographical distribution. HDV genotype 1 (HDV-1) is distributed throughout Europe, the Middle East, the Americas, and north Africa, whereas HDV genotypes 2–8 occur regionally (eg, HDV-2 in Japan, Taiwan, and Russia; HDV-3 in South America; HDV-4 in Japan and Taiwan; and HDV-5 to HDV-8 in Africa).

Comparison of Renal Function Biomarkers of Serum Creatinine and Cystatin C in HIV-Infected People on Dolutegravir-Containing Therapy.

Objective(s)HIV-1-infected Chinese patients who were treated naïve with combination dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF) group, DTG without TDF group, TDF without DTG, as well as patients switched to DTG-containing therapy from other drugs were included.DesignThe dynamics of serum creatinine, cystatin C (CysC) level, eGFRcr and eGFRCysC at the baseline, 4 w, 12w, 24w, 36w and 48w for different group of patients were collected and evaluated.MethodsChanges in serum creatinine, levels, eGFRcr and eGFRCysC were analyzed among groups and in different time-points. Intra-group correlation coefficient and Bland–Altman plot were used to compare the results of eGFRcr and eGFRCysC.ResultsThirty-seven treated-naïve HIV-patients in combined DTG and TDF group (group 1), 23 in DTG without TDF patients (group 2) and 47 patients on TDF without DTG group (control group, group 3) along with 31 patients whose ART switch to DTG-containing regimens (group 4) were collected. Serum creatinine was significantly elevated in the group 1 and group 2 instead of group 3 from baseline to 48w. Mean decreased change of eGFR calculated by serum creatinine proved the same conclusion. However, there were no differences in serum cystatin C and eGFRCysC between baseline and at 48 weeks in DTG-containing groups. Moreover, the proportion of eGFRcr decreased over 30% was significantly higher in DTG-treatment group.ConclusionWe demonstrated the clinical benefits of CysC for assessing the glomerular filtration rate when evaluating renal function in HIV-1-infected patients treated with whether DTG combined with TDF or not.

860. HIV Post-exposure Prophylaxis Availability at Small and Critical Access Hospitals in the Western Region

BackgroundPost-exposure prophylaxis (PEP) is essential to minimize the risk of human immunodeficiency virus (HIV) acquisition following an occupational or nonoccupational exposure to potentially infectious body fluids. PEP is most effective when initiated as soon as possible after HIV exposure. Patients in rural areas may rely on small (< 50 beds) and critical access (< 25 beds) hospitals for access to PEP – especially after-hours and on holidays, when outpatient pharmacies are typically closed. However, PEP medications are costly to maintain on a hospital formulary due to unpredictable use and expiration. We hypothesized that PEP availability may be variable and limited at such hospitals. MethodsThe University of Washington Tele-Antimicrobial Stewardship Program (UW-TASP) is comprised of 68 hospitals in Washington, Oregon, Arizona, Idaho, and Utah, most of which are rural and critical access. In August 2020, we surveyed UW-TASP participating hospitals and a convenience sample of other networked rural hospitals in Western states using REDCap, a HIPAA-compliant, electronic data management program. Respondents reported all antimicrobials on their hospital formulary and their hospital size. Data were reviewed by physicians and pharmacists trained in infectious diseases. Preferred PEP regimens, defined by the CDC, for adults and adolescents ≥ 13 years, included combination tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) and either raltegravir (RAL) or dolutegravir (DTG).ResultsResponses from 49 hospitals were received. Six were excluded – one was incomplete and five were excluded due to hospital size ( > 50 beds) (Table 1). The majority of hospitals (40/43, 93.0%) were critical access. Half of the hospitals’ formularies (22/43, 51.2%) contained a preferred PEP regimen. One hospital reported a non-preferred regimen. Most hospitals with a preferred PEP regimen on formulary (18/22, 86.3%) offered TDF/FTC + RAL, and the remainder (4/22, 18.2%) offered TDF/FTC + DTG. ConclusionMany small and critical access hospital formularies do not include antiretroviral agents needed for HIV PEP. Improving urgent access to these critical medications in rural communities is an opportunity for HIV prevention. Disclosures Jehan Budak, MD, Nothing to disclose Chloe Bryson-Cahn, MD, Alaska Airlines (Other Financial or Material Support, Co-Medical Director, position is through the University of Washington)

Immunological and Virological Outcomes among Treatment Experienced HIV-Infected Patients on Dolutegravir Regimen in Tanzania

Introduction The integrase inhibitor dolutegravir (DTG) has recently replaced the non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) in several Sub-Saharan African countries, including Tanzania. Since this change, there is scarce data on the current treatment outcomes focusing on treatment-experienced HIV-infected patients switched to DTG based regimens in Tanzania. Objectives This study aimed to investigate immunological and virological outcomes among treatment-experienced HIV-infected patients who were switched to DTG based regimen in Tanzania. Results We enrolled 397 patients, majority (65%) were female patients with mean age of 42.7 (95% CI; 40.7 – 44.7) years. The mean baseline CD4+ cell count was 457.1 (95% CI; 426.6 – 489.8) cells/mm3 with 8.3% of patients with CD4+ cell count <200 cells/mm3. The mean baseline viral load (VL) was 169.8 (95% CI; 128.8 – 223.9) copies/ml, whereby 20.6% had VL ≥ 1000 copies/ml. After the use of a new fixed dose combination of Tenofovir (TDF) 300 mg + Lamivudine (3TC) 300 mg + DTG 50 mg (TLD) for at least 24 weeks, the overall rate of virological suppression (<50 copies/ml) was 89.9% (95%CI 86.7% - 92.7%). The significant predictors of virological failure were overall duration on ART use (p = 0.004), duration on TDF + 3TC, and Efavirenz (EFV) (TLE) (p = 0.007), and baseline VL (p < 0.001). Conclusion TLD regimen has provided favorable preliminary results among patients who previously used TLE in HIV/AIDS treatment by showing good virological and immunological outcomes. The long-term treatment outcomes require further investigation.

Dolutegravir drug-resistance monitoring in Africa.

In many African countries, the standardised WHO-recommended combination of tenofovir and lamivudine as nucleotide reverse transcriptase inhibitors (NRTIs), with efavirenz or nevirapine as a non-NRTI (NNRTI), had been preferably used in first-line therapy among adolescents and adults living with HIV.1 However, the high levels of pretreatment drug resistance to NNRTI has prompted WHO to recommend dolutegravir as a component of first-line, second-line, and third-line antiretroviral therapy (ART) regimens.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial

Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per μL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. Gilead Sciences.