Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efavirenz (SUSTIVA, DMP 266, EFV) is a novel non-nucleoside reverse transcriptase inhibitor, which shows good inhibitory activity against HIV-1. The pharmacokinetics of efavirenz allow for once daily dosing without regard to meals of normal composition. Efavirenz is a mild inducer of CYP 3A4. Clinically significant drug interactions have been reported with medications that are metabolised via the cytochrome P450 enzymes such as indinavir and saquinavir. Results from the studies collated for submission (003, 006, 020, 024 and ACTG 364) have demonstrated the potency and durability of once daily efavirenz in combination with zidovudine (AZT) + lamivudine (3TC), indinavir (IDV), nelfinavir (NFV), IDV + 2 NRTIs, and NFV + 2 NRTIs. Efavirenz was recently approved for commercial use in the USA and has received marketing authorisation in Europe and Canada.
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PMID:Clinical history of efavirenz. 1062 35

Indinavir is a protease inhibitor used in the treatment of patients with HIV infection. Combination antiretroviral therapy with indinavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is associated with greater reductions in viral load, greater increases in CD4+ cell counts, and reduced morbidity and mortality when compared with 2 NRTIs alone. In the landmark clinical trial ACTG 320, the rate of progression to AIDS or death (primary end-point) among zidovudine-experienced patients treated with indinavir, zidovudine and lamivudine was approximately half that of patients who received only zidovudine plus lamivudine (6 vs 11%; p < 0.001). The durability of an indinavir-containing regimen was demonstrated in Merck protocol 035, an ongoing trial in which a significant proportion of patients had sustained viral suppression for up to 3 years. Merck protocol 039, also an ongoing trial, showed a greater effect on surrogate markers of HIV disease progression with indinavir-based triple therapy than with zidovudine plus lamivudine or indinavir monotherapy in patients with advanced disease (median baseline CD4+ count 15 cells/microL). Numerous additional clinical trials have established the beneficial antiviral and immunological effects of indinavir in both antiretroviral-naive and -experienced patients with HIV infection. Indinavir is associated with various drug class-related adverse events, including gastrointestinal disturbances (e.g. nausea, diarrhoea), headache and asthenia/fatigue. A lipodystrophy syndrome has been commonly reported with indinavir and other protease inhibitors combined with NRTIs, but it has also been reported in many protease inhibitor-naive patients, and a definitive causal link has not been established between the syndrome and protease inhibitors. Nephrolithiasis may develop in about 9% of patients receiving indinavir but does not appear to be associated with other protease inhibitors; <0.5% of patients receiving indinavir discontinue the drug because of nephrolithiasis, which may be the extreme end of a continuum of crystal-related renal syndromes. Additional renal problems (e.g. nephropathy) have been reported in small numbers of patients receiving indinavir. In summary, indinavir is a protease inhibitor with well documented efficacy when used as part of combined therapy in patients with HIV infection. Both US and UK treatment guidelines continue to recommend protease inhibitor-based regimens including indinavir as a first-line option. Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues. Indinavir-containing triple therapy has demonstrated positive effects not only on surrogate markers of disease progression, but also on clinical end-points of mortality and morbidity in patients with HIV disease. Protease inhibitors are a significant advance in the care of patients with HIV infection, and, in an era of evidence-based medicine, indinavir represents an important component of antiretroviral treatment strategies.
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PMID:Indinavir: a review of its use in the management of HIV infection. 1065 94

In February 1994, results of a large placebo-controlled trial of zidovudine (ZDV) use during pregnancy (ACTG 076) showed a dramatic reduction in vertical transmission of HIV. In August 1994, the Public Health Service (PHS) recommended routine ZDV use in HIV infected pregnant women and their neonates for the prevention of vertical transmission. We retrospectively reviewed vertical transmission rates of HIV in Mississippi from 1/1/90 to 8/30/94 before the PHS guidelines were released and from 9/1/94 to 12/31/97 after the PHS guidelines were released. We also reviewed data on ZDV use in HIV infected pregnant women and their neonates from 9/1/94 to 12/31/97. Antenatal, intrapartum and neonatal ZDV use increased from 61%, 59% and 73% respectively to 79%, 77% and 92% respectively. After 9/1/94, vertical transmission rates fell by 44%. Zidovudine use during pregnancy has increased in Mississippi since release of the PHS guidelines resulting in a dramatic decline in vertical transmission rates.
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PMID:The impact of zidovudine use in HIV-infected pregnant women on vertical transmission of HIV in Mississippi. 1071 Aug 94

This study examined the immediate effects of exposure to a patient education brochure concerning the risks and benefits of zidovudine (ZDV) therapy during pregnancy to reduce perinatal HIV transmission (protocol ACTG 076) on related knowledge, behavioural intentions and attitudes of women with and at-risk for HIV-infection. Self-reports were collected from 653 women of childbearing age from community family planning clinics and hospital-based HIV centres in 19 sites from nine US cities between May and November 1995. The intervention was a nine-page patient education brochure in Spanish, Creole and English versions, evently presenting the pros and cons of ZDV therapy to reduce perinatal HIV-transmission. Brochure exposure increased knowledge (p < 0.001) for all but one scale concerning ZDV resistance and increased the likelihood of women reporting intentions to take ZDV during pregnancy (p < 0.001) and to believe ZDV reduced transmission (p < 0.001). Brochure exposure had differential effects for some subpopulations. Intentions to have or terminate current or future pregnancies, knowledge about ZDV and attitudes toward ZDV varied mostly by ethnicity/race, language preference and HIV status. Pregnancy status, age, education and having an HIV-positive child had less impact on the brochure's effect, while income had no impact.
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PMID:Effects of ZDV-based patient education on intentions toward ZDV use, HIV testing and reproduction among a US cohort of women. 1071 8

The aim of our study was to evaluate changes in vertical transmission of HIV infection in Poland after introducing zidovudine prophylactic strategies. Data from the Department of Children's Infectious Diseases (a paediatric HIV referral centre) at the Medical University, Warsaw was studied. Since 1989 vertical transmission of HIV-1 has been studied in 100 children born to 91 HIV-positive mothers (2 sets of twins). Zidovudine therapy, mode and timing of delivery and their relationship to perinatal HIV-1 infection were analysed. From 1989 to 1994 the transmission rate was 31.5%. Since 1995, when recommendations based on ACTG 076 were issued, a decline in a transmission rate to 19.6% was reported. 62% (32 out of 52) mother-infant pairs received zidovudine therapy. None of those children have become HIV infected. Zidovudine chemoprophylaxis regimen reduces the risk for mother to child transmission. It should be recommended for all HIV-infected pregnant women or women in labour and their infants.
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PMID:Vertical transmission of HIV-1 in Poland. 1082 2

The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines.
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PMID:Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network. 1089 Mar 57

ACTG (AIDS Clinical Trials Group) 384 is designed to evaluate different strategies for antiretroviral treatment in HIV-1-infected individuals with no previous exposure to antiretroviral treatment. The study is a randomized, partially double-blinded, controlled trial with 980 subjects at 81 centers in the United States and Italy. The study has a factorial design that addresses the following scientific questions: (1) Does the best initial choice of therapy include both a protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) in a four-drug combination with nucleoside analogue (NRTI) drugs, or should these agents be used sequentially in three-drug combinations?; (2) Which sequence is best in a three-drug regimen-PI followed by NNRTI or NNRTI followed by PI ?; (3) Which is the best sequence of dual NRTI combinations-zidovudine plus lamivudine followed by didanosine plus stavudine, or the converse? Subjects in the three-drug combination arms are offered a salvage regimen after failure of their second regimen; subjects in the four-drug combination arm are offered a salvage regimen after failure of their first regimen. The primary endpoint of the study is the time until salvage; secondary endpoints include time to virological failure and time to toxicity-related discontinuation of therapy. A Division of AIDS Data and Safety Monitoring Board will review the trial for safety and efficacy. Control Clin Trials 2001;22:142-159
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PMID:ACTG (AIDS Clinical Trials Group) 384: a strategy trial comparing consecutive treatments for HIV-1. 1130 52

The objective of this study was to compare the effects of zidovudine and didanosine on health-related quality of life in persons with advanced HIV infection and varying duration of prior zidovudine exposure. It was designed as a substudy nested in two similar placebo-controlled active-control-arm randomized trials, using sites of the AIDS Clinical Trials Group participating in the randomized trials of zidovudine versus didanosine (ACTG 116 and 117). The patients comprised 356 participants enrolled in ACTG 116 and 117. All had HIV infection and either a CD4 count of <200 cells/mm3, or a CD4 count of <300 cells/mm3 plus symptoms of HIV disease. Participants were randomized equally within strata defined by duration of prior zidovudine therapy, to receive didanosine sachets at a dose of 500 mg daily (334 mg in subjects weighing <60 kg) or 750 mg daily (500 mg in subjects weighting <60 kg) plus inactive capsules resembling zidovudine, or to receive zidovudine capsules at a dose of 600 mg daily plus inactive sachets resembling didanosine. The main outcome measures were self-reported health-related quality of life, healthcare utilization, disability, work and symptom impact. The results showed no differences in reported symptom impact or healthcare utilization, and most measures of disability were similar. In the group with more than 8 weeks of prior zidovudine therapy, several of the health status scale scores for ongoing participants were significantly better for didanosine recipients, but average differences were small. Use of several different approaches to combining health status and survival showed no differences in the overall quality-time experiences between the treatment groups. Individuals taking zidovudine, low-dose didanosine and high-dose didanosine experienced 33, 34 and 35 weeks, respectively, in at least the typical health state if they had fewer than 8 weeks of previous zidovudine therapy, and had 23, 23 and 26 weeks, respectively, if they had more than 8 weeks previous use of zidovudine. Results did not differ when data were analysed within strata ofpatients who had any versus no prior exposure to zidovudine, or AIDS versus non-AIDS status. In conclusion, functional status and health-related quality of life were substantially similar among persons receiving either zidovudine or didanosine, regardless of the duration of prior zidovudine treatment.
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PMID:The impact of zidovudine compared with didanosine on health status and functioning in persons with advanced HIV infection and a varying duration of prior zidovudine therapy. AIDS Clinical Trials Group 116/117 Study Group. 1132 56

Immune cells secrete a variety of cytokines that have a profoundly significant influence on the immune system. For example, cytokines secreted by T-helper cells have a role in cellular immune response (Th1 cytokines) and in antibody production (Th2 cytokines). Interleukin 2 (IL-2) is used therapeutically for immune modulation, most specifically in cancer therapy. The following report describes the mechanisms of IL-2/IL-2 receptor interaction and summarizes the rationale for using IL-2 in HIV-infected patients and briefly describes recent and ongoing clinical trails using IL-2 in HIV/AIDS disease (intravenous IL-2 therapy and subcutaneous IL-2 therapy). In one study of patients with moderate stage HIV disease, subjects taking a maximum tolerated dose of IL-2 at 12 to 15 MIU/day demonstrated durable increases in CD4 counts and a near normal return in value. Relative to the published reports, low circulating CD4 counts and high HIV viral burden appeared to be independent determinants of a poor response to IL-2. However, aggressive combination therapy with IL-2 and highly active anti-retroviral therapy (HAART)(e.g., ACTG 328) holds promise for an improved immune restorative response even in patients with advanced disease.
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PMID:Interleukin-2 therapy in HIV infection. 1136 33

The HIV Infection in Women: Setting a New Agenda conference in Washington, DC, brought together researchers, providers, and HIV- positive women to discuss AIDS among women. The U.S. Public Health Service announced draft guidelines on counseling and testing of all pregnant women for HIV. These guideline were made in response to the 1994 clinical finding of ACTG 076 that the use of zidovudine (AZT, Retrovir) significantly decreases transmission of HIV from mothers to newborns. Other conference attendees expressed mistrust of AZT as a safe and effective treatment and criticized the Food and Drug Administration (FDA) for slow approval of AIDS drugs and for failing to include women in clinical trials. A representative of the Clinton administration told attendees that approximately $20 million has been allocated in the 1995 National Institutes of Health budget to study female control barriers, and an additional $724 million has been proposed for the Ryan White Care Act. In addition, participants heard information on six ongoing women's cohort studies. AIDS is now the fourth leading cause of death among American women ages 25 to 44.
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PMID:HIV conference spotlights women's concerns. 1136 49


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