- Assessment of complex genomic alterations induced by AZT, 3TC, and the combination AZT +3TC. [Journal Article]
- DCDrug Chem Toxicol 2018 Sep 12; :1-6
- Highly active antiretroviral therapy (HAART) regimens are based on the use of nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs used by patients infected with the human im...
Highly active antiretroviral therapy (HAART) regimens are based on the use of nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs used by patients infected with the human immunodeficiency virus (HIV). The use of NRTIs combinations has afforded clear clinical benefits to patients undergoing HAART. However, the combination of two NRTIs may increase the risk of genomic instability in comparison with the drugs administered individually. We analyzed the ability of zidovudine (AZT) and lamivudine (3TC), and the combination AZT +3TC to induce complex genomic alterations using the cytokinesis-block micronucleus (CBMN) assay in Chinese hamster ovary (CHO)-K1 cells. The 24-h cell treatment with individual NRTIs showed that AZT increased micronucleus frequencies and nucleoplasmic bridges (NPBs). No significant differences were observed for any parameters investigated after exposure of CHO-K1 cells to 3TC. The combination AZT +3TC significantly increased micronucleus frequencies. Analysis of interaction between these drugs suggested that antagonism occurs in all AZT +3TC concentrations. These results highlight the importance to investigate the genotoxic profile of NRTIs to develop safer intervention strategies in antiretroviral treatment protocols.
- Nevirapine Concentrations During the First Month of Life And Maternal Efavirenz Washout in High Risk HIV-Exposed Infants Receiving Triple Antiretroviral Prophylaxis. [Journal Article]
- PIPediatr Infect Dis J 2018 Sep 10
- CONCLUSIONS: NVP 4 mg/kg daily from birth provided adequate prophylactic concentrations during the first month of life in high-risk HIV-exposed neonates.
- Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. [Journal Article]
- CIClin Infect Dis 2018 Aug 31
- CONCLUSIONS: In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF.
- Reduced nevirapine concentrations among HIV-positive women receiving mefloquine for intermittent preventive treatment for malaria control during pregnancy. [Journal Article]
- ARAIDS Res Hum Retroviruses 2018 Sep 01
- Clinical trials demonstrated intermittent preventive treatment in pregnancy (IPTp) with mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected higher risk of mother to child tr...
Clinical trials demonstrated intermittent preventive treatment in pregnancy (IPTp) with mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected higher risk of mother to child transmission (MTCT) of HIV among HIV-positive women receiving MQ has also been observed. To determine if interactions between antiretroviral drugs (ARVs) and MQ could contribute to the increased MTCT observed in women receiving MQ, we performed a retrospective cross-sectional analysis of ARVs in peripheral blood plasma (maternal plasma) and cord blood plasma (cord plasma) collected at delivery from 186 mothers participating in a randomized clinical trial of MQ compared to placebo in Kenya. Plasma zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP) concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. ARVs were detected in maternal plasma and cord plasma specimens in similar proportions between the two study arms. Median concentrations of AZT and 3TC were not significantly lower in the MQ arm compared to the placebo arm for maternal plasma and cord plasma (p > 0.05). However, median NVP concentrations were significantly lower in the MQ study arm compared to the placebo study arm in both maternal plasma (1597 ng/mL vs. 2353 ng/mL, Mann-Whitney Rank Sum, p = 0.023) and cord plasma (2038 ng/mL vs. 2434 ng/mL, p = 0.048). Reduced NVP concentrations in maternal and cord plasma of women receiving MQ suggest MQ may affect NVP metabolism for both mother and infant. These results highlight the need to evaluate potential drug-drug interactions between candidate antimalarials and ARVs for use in pregnant women.
- Costs of streamlined HIV care delivery in rural Ugandan and Kenyan clinics in the search study. [Journal Article]
- AIDSAIDS 2018 Aug 20
- CONCLUSIONS: In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including VL testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90-90-90 targets.
- New Resistance Mutations to Nucleoside Reverse Transcriptase Inhibitors at Codon 184 of HIV-1 Reverse Transcriptase (M184L and M184T). [Journal Article]
- CBChem Biol Drug Des 2018 Aug 13
- CONCLUSIONS: In this study, we highlighted two new resistance mutations in vivo for NRTI resistance. The low frequency of this pathway can be related to high impairment of replicative capacity mediated by these mutations. This article is protected by copyright. All rights reserved.
- Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral therapy. [Journal Article]
- IJIndian J Med Microbiol 2018 Apr-Jun; 36(2):217-223
- CONCLUSIONS: Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients.
- Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. [Journal Article]
- JPJ Public Health Afr 2018 May 21; 9(1):767
- The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated H...
The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons.
- Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa. [Journal Article]
- DSDrug Saf 2018 Jul 24
- CONCLUSIONS: The rates of AEs were lowest among patients receiving a TDF-based second-line regimen. Patients with poorer health at the time of switch were at higher risk of AEs when receiving second-line ART and may require closer monitoring to improve the durability of second-line therapy.
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- Effects of Highly Active Antiretroviral Therapy on Renal Function and Renal Phosphate Handling in African Adults with Advanced HIV and CKD [Journal Article]
- IDInfect Disord Drug Targets 2018 07 19
- CONCLUSIONS: HIV causes kidney dysfunction with reduced phosphate excretion resulting in hyperphosphataemia but HAART improves renal function and phosphate clearance. Prolonged use of TDF can cause renal toxicity with hypophosphataemia as fractional excretion progressively increased with duration of therapy.