Combination Of Efavirenz Research Articles

Effect of Dolutegravir regimen against other regimens on some hematological parameters, CD4 count and viral load of people living with HIV infection in South Eastern Nigeria.

Appropriate usage of highly active antiretroviral therapy (HAART) suppresses human immunodeficiency virus (HIV) replication. One of such HAART is dolutegravir (DTG) containing regimen which Nigeria included in her national protocol, as the preferred first-line option, with particularly fixed dose combination of tenofovir/lamivudine/dolutegravir (TLD) in 2018. To access the impact of this regimen as against other regimens on some hematological parameters as well as cluster of differentiation 4 (CD4) count and viral load on people living with HIV infection. The study site is a health facility center supported by President Emergency Plan for acquired immunodeficiency syndrome (AIDS) Relief where people living with HIV infection (PLWHIV) visit for their routine management in Abakaliki, Ebonyi State. A hundred and twenty-two (122) subjects participated, 58 PLWHIV and 64 control subjects. CD4 + count by partec cyflow auto analyzer, while the Viral load assay was by Roche COBAS Ampriplep/COBAS TaqMan molecular systems. Full blood count determination was by Sysmex XE-2100 hematology auto analyzer, while the detection of antibody to HAART was by Petz and direct Coombs tests. Mean values of hemoglobin (Hb), Total white cell count, Lymphocytes, Monocytes and CD4 + counts of people living with HIV infection (PLWHIV) were significantly (P = .0001) lower than the control subjects. The Hb level of PLWHIV on Efavirenz combination (TDF/3TC/EFV) are comparable 123 ± 32g/l with those on Ritonavir combination (TDF/3TC/LPV/R) 136 ± 16g/l and Dolutegravir (TLD)134 ± 20.0g/l (P = .307). On the other hand, total white cell count (4.55 ± 1.99 × 109/L) of those on Efavirenz combination (TDF/3TC/EFV) and Dolutegravir (TLD) (4.53 ± 1.31 × 109/L) were significantly higher than those on Ritonavir combination (TDF/3TC/LPV/R) (4.09 ± 1.15 × 109/L). The Viral Load of PLWHIV on Dolutegravir (TLD) was significantly lower 171.57 ± 4.56 copies/mL than those on Efavirenz combination (TDF/3TC/EFV) (86,395.91 ± 27,476.57copies/mL) and Ritonavir combination (TDF/3TC/LPV/R) (81,188.83 ± 13,393.47 copies/mL), respectively. Some hematological parameters (such as Hb, total white cell counts and CD4 + count) were lower in people living with HIV than values seen in control group. The 3 regimens used in the management of HIV infection in the locality revealed comparable Packed cell volume and Hemoglobin levels. Total white cell count of those on Efavirenz and DTG is comparable with higher values than those on Ritonavir.

Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96

Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n=315) or EFV (n=315) groups. The mean age was 30.6±9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference:-4.7%, 95% CI:-9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p=0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p<0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p<0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Jiangsu Aidea Pharmaceutical Co., Ltd.

Using natural excipients to enhance the solubility of the poorly water-soluble antiretroviral, efavirenz

The anti-retroviral drug efavirenz (EFV) exhibits poor aqueous solubility which renders pharmaceutical formulation challenging. During a pre-formulation phase, involving spray drying of EFV for pediatric dosage form development, the combination of EFV with two natural excipients, pea protein isolate (PPI) and inulin (IN), was explored. In this study the effect of PPI and IN on the solubility of EFV became apparent, leading to an in-depth investigation. Equilibrium solubility studies were performed for different combinations of EFV, PPI, and IN in distilled water and buffered solutions in the presence and absence of commonly used surfactants, Tween® 20 and sodium lauryl sulfate (SLS). In the combination of EFV and PPI, PPI significantly improved EFV solubility while in the combination of EFV and IN, EFV solubility was not affected significantly. In the combination of EFV, PPI, and IN, a significant solubility improvement was noted, yet the degree of solubility improvement was less compared to the combination of only EFV and PPI. Further, the effects of PPI and IN on the solubility prove to be concentration-related. It was concluded that PPI can be used as a functional excipient to improve EFV solubility, conversely IN can be used as a drug dissolution retardant, and finally it was also concluded that it is crucial to optimize the ratio of drug to excipient to ensure optimal pharmaceutical formulation outcomes.

Liposomes as Carriers for the Delivery of Efavirenz in Combination with Glutathione-An Approach to Combat Opportunistic Infections.

Human immunodeficiency virus (HIV)-infected individuals display an enhanced production of reactive oxygen species (ROS). This reduction of antioxidant capacity in host tissues has been related to the decrease in total levels of ROS scavengers such as glutathione (GSH). Prevention of opportunistic infections due to a weakened immune system is becoming a key strategy along with HIV elimination. Research in these directions is clearly warranted, especially a combination of antiretrovirals and antioxidants to ameliorate oxidative stress, improve intracellular uptake and target viral reservoirs. Hence, we aimed to formulate liposomes loaded with the antiretroviral drug efavirenz (EFA) in the presence of glutathione, as these carriers can be engineered to enhance the ability to reach the target reservoirs. The goal of the present work was to investigate the intracellular uptake of EFA-loaded liposome (with and without GSH) by human monocytic leukemia cells (THP-1 cells) and examine cell viability and ROS scavenging activity. Results obtained provided significant data as follows: (i) treatment with EFA and GSH combination could enhance the uptake and reduce cytotoxicity; (ii) encapsulation of EFA into liposomes increased its levels in the macrophages, which was further enhanced in the presence of GSH; (iii) delivery of EFA in the presence of GSH quenched the intracellular ROS, which was significantly higher when delivered via liposomes. Data revealed that a combination of EFA and GSH encompasses advantages; hence, GSH supplementation could be a safe and cost-effective treatment to slow the development of HIV infection and produce an immune-enhancing effect.

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial

Antiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate. This multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422. Between Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of <200 copies per mL), and the median CD4 count was 466 cells per μL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050). When started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Enantioselective Separation of Antiretroviral Drug Combinations on Immobilized Polysaccharide CSPs Under Subcritical Conditions Using Supercritical Fluid Chromatography Apparatus

A stereoselective method has been developed for the chiral separation of the enantiomers of eight antiretroviral (ARV) drugs under subcritical conditions using a supercritical fluid chromatography apparatus. The ARVs: abacavir, tenofovir alafenamide, lamivudine, efavirenz, atazanavir, emtricitabine, dolutegravir and darunavir, are used to treat the human immunodeficiency virus (HIV). The antiretroviral therapy has been planned to manage and control the severity of HIV and prolong the patient’s life. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy, which slows down the development of AIDS and prevents opportunistic infections that often lead to death. The immobilized meta-substituted polysaccharide-derived carbamate columns (CSPs) have been chosen for chiral SFC separation of selected ARVs. The ARVs enantioseparation was achieved on CSPs by using different alcohol co-solvents (methanol, ethanol and isopropyl alcohol) with diethylamine (DEA) as an additive to the mobile phase. These CSPs exhibit an exceptional level of complementary chiral recognition characteristics by applying different screening and method optimization strategies. The cellulose tris(3,5-dichlorophenylcarbamate) immobilized on silica gel was found to be useful for the chiral SFC analysis of abacavir, lamivudine, efavirenz combination ARV analysis, and the method was optimized by studying the effects of different mobile phase additives, column temperatures and flow rates. The amylose tris(3-chloro, 5-methylphenyl carbamate) immobilized on silica gel was found to be useful for the chiral SFC analysis of emtricitabine, abacavir and dolutegravir combination ARV drugs.

PIN61 Cost-Effectiveness Study of the Use of Dolutegravir Compared with Efavirenz in Combination with Tenofovir and Emtricitabine, As the First LINE for the Care of Patients NEWLY Diagnosed with HIV or WHO Have NOT Started ART in Colombia.

Determine the cost effectiveness of using the dolutegravir compared to efavirenz in combination with tenofovir and emtricitabine, as the first line for the attention of newly diagnosed patients or not have started ART in Colombia. Cost-effectiveness analysis from the perspective of the third payer based on a hypothetical cohort Markov analytical model (n = 100) evaluate achievement of viral suppression, discontinuity, years of life saved in ten years how time horizon. The target population was adult frontline patients for the care of patients newly diagnosed with HIV or who did not start ART. The response parameters used were obtained from the literature and the cost contributions were obtained from the official dates (SISMED, CAC, ISS manual). Univariate sensitivity analysis and Monte Carlo type sensitivity analysis with 1000 iterations were performed. A 5% annual discount rate was applied for costs and results. Total costs of treatment were $2,708,810 USD for dolutegravir, $3,324,685 USD for efavirenz; savings from $-615,875 USD. Incremental effectiveness was years of life saved (-0,24), viral suppression (0,11) discontinuity (1.26). The cost effectiveness ratio for years of life saved was $2,589,679 USD and for discontinuity it was $490,658 USD. For viral suppression the cost effectiveness ratio dolutegravir was dominant over efavirenz. dolutegravir compared to efavirenz was shown to be a cost-effective strategy for managing PLHIV that they start antiretroviral therapy for the first time since perspective of the Colombian health system in base case conditions being dominant for the decrease in viral suppression.

Nevirapine induced Stevens Johnson syndrome

Introduction: Severe and life-threatening SJS is more common with nevirapine than with other NNRTIs&#x0D; Case presentation: A 56-year-old male patient presented with a complaint of lesions all over the body with a burning sensation for 4 days. He was on an ART regimen, containing zidovudine, lamivudine, and efavirenz combination for 4 years. But patient accidentally started nevirapine and after 10 days he developed maculopapular lesions which were diagnosed as SJS syndrome. There was a history of rash with nevirapine when ART was started initially in 2012. This incident of an adverse event could be assigned a term "probable" according to the WHO-UMC scale for causality assessment as the re-challenge was found positive.&#x0D; Conclusion: Physicians and patients must be aware of this adverse effect on early diagnosis and treatment.

Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis.

BackgroundIncreased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC).MethodsWe systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR).ResultsAmong 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR.ConclusionsThis review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization’s recommendation to avoid using NNRTIs in countries where levels of PDR are high.

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

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

Pharmacist Intervention and Quality of Life of HIV-Infected Patients in Nigeria

Assessment of quality of life of HIV-infected patients on combined antiretroviral therapy (cART) is imperative in the management of the disease. This study was done to assess the quality of life (QOL) of HIV-infected patients on cART before and after the pharmacist intervention. Consented HIV diagnosed outpatients in a tertiary health care facility in Benin City that met inclusion criteria were consecutively enrolled into the study. The QOL of these patients was determined in the four domains of WHOQOLHIV BREF instrument. The raw scores for each domain in the WHOQOL-HIV BREF were calculated by adding values of single items. The scores were computed on the scale of 0 to 100. One way ANOVA and Student t-test were used to compare means. At baseline, mean QOL values were below 73. The lowest values were in the social domain and the best values in the physical domain. The QOL values increased steadily over the period of interventions with the highest mean QOL of 93.7 in the physical domain. The improvement in QOL was significant at 6 and 9 months following interventions (p &lt; 0.001). The values obtained are expressed in percentage. There was no statistically significant difference between male and female patients on cART in all domains of QOL following the intervention. Patients on Tenofovir + Emtricitabine + Efavirenz combination therapy had significantly higher scores in all the domains of QOL as compared with other drug combinations used in the management of the patients. The only educational level of the patients was significantly associated with the patients’ QOL. The intervention in this prospective study was a success, as it led to increasing in QOL for the patients on cART from the baseline level to the end of the 9th month.Bangladesh Pharmaceutical Journal 20(2): 132-138, 2017

Highly active antiretroviral therapy adherence among perinatally infected HIV adolescents at a teaching hospital in Ghana

ABSTRACTIncreased accessibility to Antiretroviral Therapy (ART) has resulted in the decline of deaths among children with Perinatally Infected Human Immunodeficiency Virus (PIHIV). Their adherence to Highly Active ART (HAART) is vital for their survival and quality of life. This study aimed at determining HAART medication adherence among adolescents with PIHIV. The study was cross-sectional conducted from September 2015 to January 2016 at a teaching hospital in Ghana. It involved 106 adolescents aged 10–20 years. Morisky’s eight-item medication adherence scale was adapted and used to determine the adherence level. Factors influencing adherence were also determined by interviewing the adolescents. EpiData 3.1 and Stata version 12 were used for data entry and analysis respectively. There was low adherence in 76.4% of the adolescents, and the HAART regimen associated with high medication adherence was tenofovir, lamivudine and efavirenz combinations (p = .011). Forgetfulness (p = .001) and inability to come for refill (p = .013) were the main factors associated with low adherence. However adherence was not significantly associated with a lack of medication supply or stigmatization. Addressing the modifiable factors found in this study to be associated with low adherence are essential interventions for their long-term quality of life.

Abnormal coagulation profile in people living with HIV-AIDS on combined Antiretroviral Therapy: findings from a case-control study in the Ho municipality, Ghana

Introduction : Although combined Anti-Retroviral Therapy (cART) has improved the quality of life and survival in people living with HIV-AIDS (PLWHA), there have been reports of increased non-AIDS related co-morbidities such as coagulopathies. The objective of this study was to assess the effect of cART on the coagulation profile of PLWHA. Methods : This case-control study recruited 110 PLWHA (65 patients on cART, and 45 cART naive patients) from the antiretroviral therapy unit of Volta Regional Hospital, Ho. Blood was collected for prothrombin time (PT), activated partial thromboplastin time (APTT)and platelet count. Results : cART naive individuals had a high PT (p <0.001; 17.2 vs 13.8) and APTT (p = 0.081; 59.7 vs 55.3) compared to their counterparts on cART. Also, INR was significantly lower in cART-treated PLWHA (p<0.001). Platelet count was high in participants on therapy compared to their naive counterparts (204.7 vs 193.6, p = 0.402). Patients on zidovudine + nevirapin + efavirenz therapy had a significantly lower PT compared to those on zidovudine + lamivudine + efavirenz therapy {p = 0.02, 13.23 vs 14.66}. Additionally, PLWHA on zidovudine + nevirapin + efavirenz had reduced APTT compared to those on zidovudine + lamivudine + efavirenz therapy, or zidovudine + lamivudine+ nevirapine therapy (p = 0.058; 47.55 vs 56.81 vs 56.85 respectively). Conclusion : HIV infection adversely affects the coagulation profile in PLWHA which improves with cART. Barring the existence of other comorbidities, cART with zidovudine + nevirapin + efavirenz combination could be the treatment of choice as it significantly improves the coagulation profile in PLWHA.

Antiretroviral pill count and clinical outcomes in treatment-naïve patients with HIV infection.

Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations.

Evaluation of HIV therapeutic agents on immunological, lipid and lipoprotein indices in Ghanaian HIV-1 infected patients

HIV-1 infected patients initiating antiretroviral therapy (ART) in Ghana are placed on one of the two most commonly used non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine (NVP) and efavirenz (EFV), in combination with a nucleoside reverse transcriptase inhibitor backbone of either combivir (CBV) or stavudine (d4T)/lamivudine (3TC). This study sought to evaluate the effect of these therapeutic agents on weight, immunological, lipid and lipoprotein changes as well as the atherogenic indices of Ghanaian HIV-1 infected patients. This observational study was carried out at the ART clinic of the Regional Hospital, Bolgatanga in the Upper-East region of Ghana from September 2008 to September 2009 comprising 61 HIV-1 infected patients who were initiated on NVP or EFV in combination with either CBV or d4T/3TC. Out of the 61 enrolled patients, 27(44.3%) were on NVP and 34(55.7%) were on EFV. Within the NVP group, 16 (59.3%) were on CBV and 11(40.7%) on d4T/3TC whilst the EFV group had 26(76.5%) on CBV and 8 (23.5%) on d4T/3TC. Percentage changes in lipid profile components comprising total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) was assessed over the 12-month period. Percentage changes in atherogenic index expressed as TC/HDL-c and LDL-c/HDL-c was also estimated. NVP elicited a 10.2% increase in weight compared to EFV and this was associated with CBV combination use. EFV further elicited a 9.1% increase in TC, 1.2% increase in TG, 39.3% increase in LDL-c and a 4.1% increase in HDL-c which resulted in concomitant percentage increases in TC/HDL-c (22%) and LDL-c/HDL-c (47.3%). CBV as a NRTI component of EFV elicited a 4.3% increase in TC/HDL-c and a 16.6% increase in LDL-c/HDL-c compared to d4T/3TC whilst conversely, d4T/3TC elicited a 3.6% increase in TC/HDL-c and a 34.0% when used in combination with NVP. NVP combination therapy elicited improvement in weight compared to EFV combination therapy for the different categories of patients. The less atherogenic lipid profile observed in patients taking NVP in comparison to those taking EFV and the reduction in CHD risk associated with NVP + CBV combination therapy observed in this study should be factored into considerations taken when selecting the most appropriate ART regimen for treatment naïve HIV-1 infected patients.Journal of Medical and Biomedical Sciences (2016) 5(3), 13-27Keywords: HIV-1, Antiretroviral therapy, Immunological, Lipids, Atherogenic indices, Bolgatanga, Ghana

Simultaneous HPLC Determination of Efavirenz, 8-hydroxy Efavirenz, Neostigmine and Comparison of their Separation Using a C18 and Biphenyl Column through Pharmacological Evaluation

A simple, rapid and stable high performance liquid chromatography method for a combination of efavirenz, its major metabolite 8-hydroxy efavirenz and neostigmine was developed and validated. The drugs individually and in combination, were analysed using an Agilent 1260 high performance liquid chromatography coupled with variable wavelength detector. Successful separation of combined drugs were achieved by gradient elution on a reverse-phase C18 Phenomenex Evo 100A column (150i?´4.6 mm, 2.6 μ), by gradient elution using a mobile phase consisting of water:acetonitrile at 0.6 ml min-1 flow rate, detection wavelength 245 nm, column oven temperature 27° and injection volume 15 μl. The same method was also deployed on a Restek Ultra biphenyl column (150i?´4.6 mm, 5 μ) to compare the levels of separation of the drugs and the metabolite. The chromatographic retention times were consistent at 8.75, 9.33 and 10.20 min for efavirenz, 8-hydroxy efavirenz and neostigmine, respectively. Polynomial regression data for the calibration plots exhibited linear relationship (correlation coefficient=0.999) in the range of 2.5-150 μM for both efavirenz and 8-hydroxy efavirenz, and the lower limit of detection and lower limit of quantification at 32 μM and 96.97 μM for efavirenz and 29.49 μM and 89.38 μM for 8-hydroxy efavirenz, respectively. Pharmacological drug metabolism evaluation was done on the method specificity using in vitro incubations using human liver microsomes and linearity was established for the 30, 45 and 60 min incubations (correlation coefficient=0.97). The method provides a necessary tool to investigate herb and drug-drug interactions and can be applied for quantifying the drugs in in vitro drug metabolism assays.

Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40–70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur & 61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88–124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39–4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6–3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

Tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients treated for tuberculosis: the ANRS 129 BKVIR trial.

HIV-infected patients with TB need simplified, effective and well-tolerated antiretroviral regimens. The French ANRS 129 BKVIR open trial evaluated the once-daily tenofovir DF/emtricitabine and efavirenz combination, started within 12 weeks after TB treatment initiation, in antiretroviral-naive HIV-1-infected patients. Success was defined as an HIV-1 RNA <50 copies/mL and TB cure at 48 weeks. TB was confirmed microbiologically (90%) or histologically (10%) in 69 patients (71% male; median age 43 years; 54% born in Africa). The median time between TB treatment initiation and antiretroviral therapy was 8 weeks (range 1-22 weeks). At baseline, median HIV-1 RNA was 5.4 log10 copies/mL and median CD4 cell count 74 cells/mm(3). In the ITT analysis, combined success at week 48 was achieved in 57/69 patients (83%, 95% CI 74-92). Twelve patients did not achieve virological success, and TB was not cured in one of them. Among the 47 patients who fully adhered to the strategy, the success rate was 96% (95% CI 90-100) and was not affected by low rifampicin and isoniazid serum concentrations. Forty-nine serious adverse events were reported in 31 patients (45%), and 11 led to antiretroviral drug interruption. All adverse events resolved. The immune reconstitution inflammatory syndrome occurred in 23 patients (33%, 95% CI 22-44), and was associated with a low baseline BMI (P = 0.03) and a low haemoglobin level (P = 0.02). These results support the use of tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients with TB.

HAART, DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon.

BackgroundTuberculosis is the commonest infection among HIV/AIDS patients. This co-infection constitutes a major death threat in the world. There is paucity of data about renal disease amongst patients on HAART and DOTS therapy in Cameroon.MethodsThis was a hospital-based cross-sectional study in the Buea, Limbe and Kumba government Hospitals. Spectrophotometric method was used for the quantitative determination of serum creatinine, urea, albumin and total protein levels. Glomerular filtration rate was estimated using the MDRD method. The student’s t test, ANOVA and logistic regression were used to analyse the data.ResultsOut of 200 participants, 101 (50.5 %) were males. The ages ranged from 21 to 65 years with a mean age of 38.04 ± 10.52 years. Compared to adults on DOTS alone, adults on HAART alone had a significantly higher prevalence of eGFR <60 ml/min/1.73 m2 (10/70 (14.3 %) vs. 1/70 (1.4 %), OR = 11.5 [1.4–92.5], p = 0.02) while more participants on HAART/DOTS had significantly higher serum creatinine (18/60 (30 %) vs 10/70 (14.3) OR = 2.57 [1.08–6.12], p = 0.033). Though participants on HAART/DOTS combined therapy had low eGFR, the association was not statistically significant (OR = 6.27, 95 % CI;0.71–55.27, p = 0.098). Participants on the Zidovudine, Lamivudine, Nevirapine regimen showed a statistically significant difference in the mean serum creatinine and albumin levels between the HAART/DOTS combined therapy and HAART group (p = 0.0219 and 0.0001 respectively).ConclusionCompared to adults on DOTS, adults on HAART were more likely to have renal dysfunction (eGFR <60 ml/min per 1.73 m2). Adult on a combination of HAART and DOTS had a similar prevalence of renal dysfunction as those on HAART alone. This study showed that the use of the HAART regimen (Tenofovir, Lamivudine and Efavirenz combination) among the HAART treated adults was nephrotoxic. However, other combined HAART and DOTS regimens had no nephrotoxic effect. Abnormal kidney function can be associated with HAART use.

A Validated Method for Quantification of Efavirenz in Dried Blood Spots Using High-Performance Liquid Chromatography–Mass Spectrometry

Efavirenz (EFV) is one of the preferred components of first-line antiretroviral treatment. EFV is characterized by a long plasma half-life (40-55 hours) with large interpatient variability, which raises the potential for individualization of therapy. Analyses of EFV levels in plasma require specialized facilities (cold storage/transport) which, in resource-limited settings, can be problematic; dried blood spots (DBS)-EFV measurements thus provide a cheap easy alternative for therapeutic drug monitoring. Our aim was to develop and validate a liquid chromatography-mass spectrometry method to quantify EFV in DBS collected as part of clinical trials in resource-limited settings. DBS for standards, quality control samples, and patient samples were excised and then extracted with ethyl acetate/n-hexane (50/50 vol/vol) after addition of internal standard hexobarbital, and 1 mol/L K2CO3. The extract was evaporated to dryness, the residue reconstituted in mobile phase and analyzed directly by liquid chromatography-mass spectrometry. Gradient elution was on a reverse-phase C18 column using 1 mmol/L ammonium acetate in water and acetonitrile. Quantification was by selected reaction monitoring in negative ionization mode. DBS samples were obtained at several time points over 24 hours from HIV+ patients on either 400 or 600 mg EFV in combination with emtricitabine/tenofovir. The internal standard and EFV eluted at 2.68 and 3.54 minutes, respectively in a 5-minute run time. Matrix effects were minimal (-5.4%). Calibration curves were validated over a concentration range of 25-5000 ng/mL. Intra-assay and interassay variations ranged between 6.7% and 8.7% for imprecision and 100.3% and 104.2% for accuracy. Mean recovery was >64%. The DBS data showed a strong positive correlation with a validated plasma EFV assay (R = 0.9764, P < 0.001). EFV concentrations from DBS were approximately 42% lower than the paired plasma values, and the ratio of blood/plasma did not change over the dosing interval. The validated assay is now routinely applied to clinical samples measuring DBS EFV for pharmacokinetic analysis. The methodology is robust, accurate, and sensitive.