Solubility Enhancement Methods Of Efavirenz : A Review

Snapshots for July 2007

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

Approximately 30 years ago, in June 1981, it was reported from theCenter forDiseaseControl andPrevention (CDC) that five, otherwise healthy, homosexual men in California had presented with pneumonia caused by Pneumocystis jiroveci pneumonia, a rare disease seen exclusively in individualswith a severely suppressed immune system. Several reports confirmed the initial observation and lent support to the possibility that a new sexually transmitted, infectious agent was circulating within the gay community in the United States. The clinical condition was named acquired immunodeficiency syndrome (AIDS). Two years later, a research team at the Institut Pasteur under the guidance of Francoise Barre-Sinoussi and Luc Montagnier isolated human immunodeficiency virus (HIV), the causative agent of AIDS, from a lymph node biopsy of a French patient. The isolation and characterization of HIV paved the way for the design of diagnosticmethods to identify the virus in blood andbloodproducts and towards the development of novel antiretroviral treatment (ART) to control HIV replication in infected patients. For their discoveries, Barre-Sinoussi and Montagnier were awarded the Nobel Prize in Physiology and Medicine in 2008.

HIV Disease and Aging

Psychomotor slowing predicts the development of HIV-1-associated dementia, AIDS, and death independent of immune status. We retrospectively selected all patients who showed pathologic psychomotor slowing as a sign of central nervous system (CNS) dysfunction before the onset of therapy and who were then treated with nonnucleoside reverse-transcriptase inhibitors-either efavirenz (EFV) (n = 65 patients) or nevirapine (NVP) (n = 39 patients), each given in combination with two nucleoside analogues (NAs). Patients who were treated only with two NAs (n = 66) served as controls. Patients were observed for 6 months. Both EFV and NVP combinations improved CNS function as determined by electrophysiologic motor tests. The therapeutic effects of EFV and NVP did not depend on the type of NA added. Although results did not reach significance, NVP combinations were more effective than EFV combinations or therapy regimens with NAs alone in patients who were naïve to all antiretroviral therapy. EFV and NVP combinations were equally effective in patients pretreated with highly active antiretroviral therapy, including protease inhibitors.

Introduction: Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a disease of the human immune system. The drugs used in the treatment of HIV/AIDS are known to cause adverse effects, therefore this study was carried out for the monitoring and evaluation of adverse drug reactions (ADRs) caused by the use of antiretroviral drugs in patients of HIV/AIDS. Methods: A prospective, observational, cross sectional study was done in Andaman & Nicobar Islands institute of medical sciences, to monitor ADRs caused by Antiretroviral therapy (ART) over a period of 10 months in 120 patients of HIV/AIDS. Out of 120 patients, 84 had ADR’s. The data collected was filled in the spontaneous ADR reporting forms and Causality assessment was done using the WHO-UMC and Naranjo scale, seriousness was considered as per the ADR reporting form. Results: The study shows that out of 84 patients with ADR’s, 52 patients (61.9%) reported at least one ADR. 68 ADR’s (80.9%) were attributed to the tenofovir + lamivudine + efavirenz regimen. Most of the ADRs were from the system organ class of neurological disorders as 55 patients (65.4%) and 16 patients (19%) were having gastrointestinal ADR’s (19.44%) followed by Cutaneous ADR’s in 5 patients (5.9%). Causality assessment by WHO-UMC scale revealed most of the reactions as ‘possible’ (99.2%) while Naranjo scale assessed most of them as ‘probable’ (69.8%). Conclusion: Antiretroviral drugs have a huge potential for causing ADRs specially neurological and gastrointestinal. Active Pharmacovigilance is vital in recognizing such reactions to ensure timely management and optimal therapeutic outcomes.

Human Immunodeficiency Virus: The Initial Physician-Patient Encounter

The introduction of antiretroviral therapy (ART) led to huge reductions in human immunodeficiency virus (HIV)-related deaths, turning HIV-infection into a chronic condition. Attention is now turning to quality of life for patients on lifelong ART treatment, reflecting on the safety of antiretroviral drugs. In sub-Saharan Africa, efavirenz (EFV) forms the preferred first-line ART but adverse drug events have also been reported. We express our concern on EFV-based regimens being part of mass rollout programs without full attention to toxicities. EFV is associated with various neuropsychiatric adverse events (AEs). If EFV use is not monitored, a huge burden of neuropsychiatric AEs and elevated risk of drug resistance due to nonadherence are likely to follow. A monumental EFV-based ART regimen rollout program, through the UNAIDS 90-90-90 and option B plus programs/approaches, is planned, which will more than double the number of patients on EFV-containing ART. According to this ambitious treatment target, by 2020, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained ART; and 90% of all people receiving ART will have viral suppression. On the other hand, HIV patients of African origin are predisposed to developing EFV-induced neuropsychiatric AEs due to specific CYP2B6 genetic variants causing impaired metabolism of EFV. It is our considered opinion that the potential quantitative and qualitative burden of EFV-induced neuropsychiatric AEs, which can vary from person-to-person and between populations, deserve special attention and action during the ART rollout program. We here make a case for Africa in particular where we project the burden of neuropsychiatric AEs to be greatest. We advocate for surveillance of neuropsychiatric AEs due to EFV therapy, incorporation of pharmacogenetics testing for CYP2B6 to assist in EFV dosing, and measurement of plasma EFV concentration, as a three-pronged rational therapeutic drug monitoring strategy to guide EFV treatment toward precision medicine.

Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling.

2.0 Recommendations and auditable outcomes

Addressing HIV-1 latency with Flow-FISH: Finding, characterizing and targeting HIV-1 infected cells.

BackgroundThe Chinese government has provided health services to those infected by the human immunodeficiency virus (HIV) under the acquired immunodeficiency syndrome (AIDS) care policy since 2003. Detailed research on the actual expenditures and costs for providing care to patients with AIDS is needed for future financial planning of AIDS health care services and possible reform of HIV/AIDS-related policy. The purpose of the current study was to determine the actual expenditures and factors influencing costs for untreated AIDS patients in a rural area of China after initiating highly active antiretroviral therapy (HAART) under the national Free Care Program (China CARES).MethodsA retrospective cohort study was conducted in Yunnan and Shanxi Provinces, where HAART and all medical care are provided free to HIV-positive patients. Health expenditures and costs in the first treatment year were collected from medical records and prescriptions at local hospitals between January and June 2007. Multivariate linear regression was used to determine the factors associated with the actual expenditures in the first antiretroviral (ARV) treatment year.ResultsFive ARV regimens are commonly used in China CARES: zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP), stavudine (D4T) + 3TC + efavirenz (EFV), D4T + 3TC + NVP, didanosine (DDI) + 3TC + NVP and combivir + EFV. The mean annual expenditure per person for ARV medications was US$2,242 (US$1 = 7 Chinese Yuan (CNY)) among 276 participants. The total costs for treating all adverse drug events (ADEs) and opportunistic infections (OIs) were US$29,703 and US$23,031, respectively. The expenses for treatment of peripheral neuritis and cytomegalovirus (CMV) infections were the highest among those patients with ADEs and OIs, respectively. On the basis of multivariate linear regression, CD4 cell counts (100-199 cells/μL versus <100 cells/μL, P = 0.02; and ≥200 cells/μL versus <100 cells/μL, P < 0.004), residence in Mangshi County (P < 0.0001), ADEs (P = 0.04) and OIs (P = 0.02) were significantly associated with total expenditures in the first ARV treatment year.ConclusionsThis is the first study to determine the actual costs of HIV treatment in rural areas of China. Costs for ARV drugs represented the major portion of HIV medical expenditures. Initiating HAART in patients with higher CD4 cell count levels is likely to reduce treatment expenses for ADEs and OIs in patients with AIDS.

Basic Facts About HIV And AIDS

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

Idiopathic AIDS Enteropathy and Treatment of Gastrointestinal Opportunistic Pathogens