Acquired Immunodeficiency Syndrome Drug Research Articles

PPACA and Low-Income People Living with HIV: 2014 Qualified Health Plan Enrollment in a Medicaid Nonexpansion State.

People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often are uninsured or underinsured, and they may benefit from the Patient Protection and Affordable Care Act (PL 111-148) and its improved access to medical care. Safety net programs, such as AIDS Drug Assistance Programs (ADAP) funded through the Ryan White HIV/AIDS Program, which serve low-income people living with HIV, are incorporating Patient Protection and Affordable Care Act Marketplace-qualified health plans (QHPs) and helping to fund patients' participation. This changing landscape differs from state to state, and one main element contributing to the differing situations is whether a state elected to expand Medicaid. This review examines QHP enrollment of ADAP clients in Virginia, a Medicaid nonexpansion state, and explores some issues that affect people living with HIV in other Medicaid nonexpansion states. Virginia is a leader in the shift of ADAP healthcare delivery from direct medication provision to purchasing QHPs. Virginia ADAP clients accounted for approximately 2% of ADAP clients nationally, but they represent 17% of ADAP clients enrolled in QHPs nationwide. Ensuring good HIV care of the ADAP population is important to each patient's personal longevity, the public health, and the efficient use of healthcare dollars. As healthcare delivery models shift, the effects on patients and health outcomes achieved should be monitored, particularly for chronic diseases such as HIV.

Anti-HIV-1 drug toxicity and management strategies

Anti-HIV-1 drug toxicity and management strategies Bechan SharmaDepartment of Biochemistry, University of Allahabad, Allahabad, IndiaAbstract: Antihuman immunodeficiency virus type 1 (anti-HIV-1) medications have helped millions of HIV-1-infected people lead longer and healthier lives. The goal of HIV-1 treatment is to reduce the number of virions in the body of infected individuals and to prevent rapid destruction of CD4+ T-lymphocyte cells, thus protecting the immune system. Most of the anti-HIV-1 drugs in practice are designed using viral reverse transcriptase (HIV-1RT), protease, and integrase as targets. These drugs that inhibit the activities of HIV-1RT, viral protease, and integrase are therefore known as anti-HIV-1RT, antiprotease, and anti-integrase molecules, respectively. The US Food and Drug Administration has approved 22 anti-HIV-1/acquired immunodeficiency syndrome (AIDS) drugs for clinical use by HIV-1-infected individuals and AIDS patients. Among the drugs, most of the nucleoside analogs (excluding two isomers of 3TC, (-)3TC and (+)3TC, which are shown to be less toxic in cell culture) exhibit clinical complications that pose a threat to chemotherapy. The toxicity of these molecules arises due to their negative impact on the activities of human mitochondrial chromosomal DNA polymerases (a, d, ß, and e) in general and DNA polymerase γ in particular. Other anti-HIV-1 regimens are also reported to cause toxicity. The range of toxicity extends from mild to life-threatening levels. The prolonged use of zidovudine (3′-azido-3′-deoxythymidine [AZT] or Retrovir), which was first approved in 1987 as a nucleoside analog reverse transcriptase inhibitor, has been reported to cause severe hematologic toxicity, including severe anemia, granulocytopenia, and symptomatic myopathy. Many other drugs that are often used in combination with AZT have similar toxicities. The newer antiretrovirals (ARVs), such as 2′,3′-dideoxycytidine, 2′,3′-dideoxyinosine, and 2′,3′-dideoxy-2′,3′-didehydrothymidine, which exhibit analogous mechanisms of action and similar toxicities to AZT, have not been studied extensively. Acyclovir and gancyclovir can cause severe nausea and vomiting. Some of these ARVs when taken during pregnancy may generate teratogenic effects. Similarly, use of antiproteases in highly active ARV therapy causes hepatotoxicity, which poses a severe risk to the patients. In addition, application of fusion inhibitors and anti-integrases induces strong side effects in HIV-1-infected or AIDS patients. The present review illustrates a comprehensive analysis of the existing literature on the toxicity of anti-HIV-1/AIDS drugs, their mechanisms of action, and possible management strategies to combat this problem.Keywords: HIV-1, AIDS, anti-HIV-1RT drugs, antiproteases, anti-integrases, fusion inhibitors, dosage, toxicity, management

Optimizing Resource Allocation in United States AIDS Drug Assistance Programs

US acquired immunodeficiency syndrome (AIDS) Drug Assistance programs (ADAPs) provide medications to low-income patients with human immunodeficiency virus (HIV) infection/AIDS. Nationally, ADAPs are in a fiscal crisis. Many states have instituted waiting lists, often serving clients on a first-come, first-served basis. We hypothesized that CD4 cell count-based ADAP eligibility would improve ADAP outcomes, allowing them to serve more-diverse patient populations and to prioritize persons who are at greatest risk of HIV-related mortality. We used Massachusetts ADAP administrative data to create a retrospective cohort of Massachusetts ADAP clients from fiscal year 2003. We then used a model-based analysis to apply potential eligibility criteria for a limited program and to compare characteristics of patients included under CD4 cell count-based and first-come, first-served eligibility criteria. In fiscal year 2003, Massachusetts ADAPs served 3560 clients at a direct cost of 10.3 million dollars. With use of CD4 cell count-based eligibility (with an eligibility criterion of a current or nadir CD4 cell count < or = 350 cells/microL), it would have served 2253 clients (37% fewer than in fiscal year 2003) and appreciated savings of 2.7 million dollars. Given the same budget constraint and using first-come, first-served eligibility, Massachusetts ADAPs would have served 2406 clients (32% fewer than in fiscal year 2003). The first-come, first-served approach would have excluded patients with median CD4 cell count of 257 cells/microL (interquartile range, 124-377 cells/microL) in favor of serving patients with median CD4 cell count of 659 cells/microL (interquartile range, 511-841 cells/microL). In addition, a CD4 cell count-based scheme would have served a greater proportion of nonwhite individuals (65% vs. 55%; P<.0001), non-English speakers (24% vs. 19%; P=.03), and unemployed people (69% vs. 61%; P=.0009), compared with the population that would have been served by a first-come, first-served policy. With limited resources, ADAPs will serve more-diverse populations and patients with significantly more advanced HIV disease by using CD4 cell count-based enrollment criteria rather than a first-come, first-served approach.

Effects Of Case Management And New Drugs On Medicaid AIDS Spending

This study evaluates the effects of Florida's participation in the Medicaid acquired immunodeficiency syndrome (AIDS) home and community-based waiver and the use of recently developed AIDS drugs on spending per Medicaid beneficiary. We find that monthly Medicaid spending for waiver non-participants was significantly higher than was spending for waiver nonparticipants. The major reason for the cost difference is that nonwaiver enrollees incurred significantly higher inpatient costs than did those enrolled in the waiver. Although waiver enrollees had higher drug spending, these represent only a fraction of the higher inpatient costs incurred by nonwaiver enrollees. Thus, it appears that adherence to appropriate medications reduces the need for inpatient care. The case management approach of the AIDS waiver may have similar effects for persons with other chronic diseases.

Synthesis, Enzymatic Hydrolysis, and Anti-HIV Activity of AZT−Spacer−Curdlan Sulfates

An AIDS (acquired immunodeficiency syndrome) drug, azidothymidine (AZT), was bound by an ester bond onto curdlan sulfate having both anti-HIV activity and the property of accumulating in lymphoid tissues to produce a series of biodegradable AZT−aliphatic-dicarboxylate−curdlan sulfates (designated as AZT−spacer−curdlan sulfates). When the carbon number of the alkylene group was 2−12, AZT−spacer−curdlan sulfates exhibited high anti-HIV activities in the EC50 range of 0.04 − 0.21 μg/mL and low cytotoxicities of CC50 of more than 1000 μg/mL. AZT−dodecanedicarboxylate−curdlan sulfate with the highest anti-HIV activity was easily hydrolyzed by esterase−enzymatic hydrolysis to release free AZT. Furthermore, an acidically released AZT from curdlan sulfate exhibited its high anti-HIV activity. AZT−dodecanedicarboxylate−curdlan sulfate showed a low anticoagulant activity of 7 unit/mg.

The impact of legislative changes on acquired immunodeficiency syndrome drug development

The impact of legislative changes on acquired immunodeficiency syndrome drug development

Risk for toxoplasmic encephalitis in AIDS patients in Yugoslavia

Objectives: To determine the incidence of toxoplasmic encephalitis (TE) in patients with acquired immunodeficiency syndrome (AIDS) in Yugoslavia and to analyze the contribution of sex, age, human immunodeficiency virus (HIV) transmission risk factors, CD4+ T -cell count, and systemic Pneumocystis carinii pneumonia (PCP) prophylaxis as risk factors for the development of TE. Design: Retrospective chart review of 288 (72%) of the 399 AIDS patients diagnosed in Yugoslavia during the 5-year period 1991 to 1995. Inclusion criteria included serology for toxoplasmosis performed prior to the TE episode. Results: Toxoplasma gondii-specific IgG antibodies were detected in 127 of the 288 AIDS patients (44.1 %) tested serologically (including all with neurologic abnormalities). A total of 31 patients developed TE, indicating a TE overall attack rate of 7.8%. Of these, 29 TE episodes occurred in the T, gondii-seropositive patients (22.8%), significantly more often than in the T. gondii-seronegative ( χ 2 = 34.423, P < 0.005), among which TE occurred in two ( 2 161 , 1.24%). By survival analysis, the cumulative incidence of TE in the T. gondii-seropositive patients was 32.7% for 60 months (30% for 24 months). Although not associated with age, sex, or HIV transmission risk factor, the risk for TE increased with the decrease in the CD4+ Tcell count (relative risk [RR] = 0.276, 95% confidence interval [CI] = 0.198-0.673, P = 0.0013), and was reduced in patients on systemic PCP prophylaxis (RR = 0.222, 95% CI = 0.068−0.642, P = 0.006). Conclusions: In areas of high exposure to T. gondii, such as Yugoslavia, timely serology for toxoplasmosis in patients with AIDS and subsequent drug prophylaxis to prevent reactivation in seropositive patients is recommended.

NIH conference. Recent advances in the management of AIDS-related opportunistic infections.

Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials. Several agents are now available to treat diseases caused by Pneumocystis carinii, and corticosteroids have become a useful adjunct to antimicrobial agents in the treatment of P. carinii pneumonia. Although the treatment of toxoplasmosis remains a challenge, alternatives to sulfadiazine and pyrimethamine are now available. Mycobacterial infections, particularly with Mycobacterium tuberculosis, have become an increasing problem for patients with AIDS, and both old and new combination drug regimens are being used. Cytomegalovirus disease, until recently an untreatable problem, can now at least be partially managed with antiviral agents. The use of more complete prophylactic regimens may decrease the morbidity and mortality from opportunistic infections.

AIDS, HIV infection, and illicit drug use within inner-city families and social networks.

Drug use is commonly depicted and treated as an individual problem. This study describes the extent of drug use, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS) among drug users' sexual partners and family and household members in order to broaden considerations of risk. Social network charts and structured interviews were administered to 126 women (predominantly African American and Latino) enrolled in methadone treatment. The charts elicited the prevalence of drug use and HIV infection among subjects' family and household members. Drug use and HIV/AIDS permeated subjects' sexual, familial, and household relationships. More than half of the women who resided with a sexual partner reported that their partners currently used drugs. Almost one third of the subjects' siblings were drug users. Of the 715 total siblings (all subjects plus their siblings), 69 (9.7%) were known to be HIV positive or to have an AIDS diagnosis. The sexual, familial, and household expressions of drug use underscore the notion that drug use and attendant risks, including but not limited to HIV infection, might be usefully viewed and treated as an inter- and intracommunity problem rather than as an exclusively individual one.

Reviews and Notes

Literature of Medicine1 January 1994Reviews and NotesD. Peter Drotman, MD, MPHD. Peter Drotman, MD, MPHCenters for Disease Control and Prevention, Atlanta, GA 30333Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-1-199401010-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Against the Odds: The Story of AIDS Drug Development, Politics and ProfitsPeter S. Arno and Karyn L. Feiden. 314 pages. New York: HarperCollins; 1992. $23.00.The acquired immunodeficiency syndrome (AIDS) has produced many changes in medicine as well as in society. Developments as diverse as safer sexual practices, universal precautions for infection control, and the cost of health insurance may come to mind first, but many other aspects of our social and medical lives have already been influenced by the AIDS virus and the epidemic it has spawned. AIDS has also changed the way we develop, approve, and market ... Author, Article, and Disclosure InformationAffiliations: Centers for Disease Control and Prevention, Atlanta, GA 30333 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1994Volume 120, Issue 1Page: 94KeywordsAIDSDrugsHealth insuranceInsulinPatient advocacyPenicillinResearch fundingSchizophreniaScientistsToxicity ePublished: 15 August 2000 Issue Published: 1 January 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Clarithromycin and Other Antimicrobial Agents in the Treatment of Disseminated Mycobacterium avium Infections in Patients With Acquired Immunodeficiency Syndrome

Disseminated infection with Mycobacterium avium is common with late-stage acquired immunodeficiency syndrome (AIDS), and no antimicrobial agent has been found to be clearly effective. A multicenter open trial was conducted to assess the antimicrobial activity and clinical efficacy of clarithromycin--a new macrolide antibiotic--against disseminated M avium in 77 patients with late-stage AIDS. Blood cultures were taken at baseline and during treatment; side effects were also evaluated. Mycobacterium avium was eradicated from blood cultures in 11 (63%) of 16 evaluable patients receiving daily doses or 500 or 1000 mg, (n = 21) and in 45 of 46 (98%) of those receiving 1500 or 2000 mg (n = 56). Eradication after 2 months was influenced by continuity of drug treatment; 36 of 42 patients with no relapse had received continuous treatment vs six of 14 patients whose drug treatment had been stopped for 7 days or longer. After 2 to 7 months of treatment, acquired resistance associated with relapse was observed. Drug side effects were elevated liver enzyme levels (26%) and impaired hearing (4%). Concomitant AIDS drugs had no favorable effect on outcome and may have worsened liver toxicity. Clarithromycin has bacteriologic efficacy against M avium infection in late-stage AIDS, although drug resistance eventually develops. Further studies are needed to investigate safe, effective concomitant drugs.

A Different Kind of Drug War

A Different Kind of Drug War

Aerobic Exercise Training in an AIDS Risk Group*

Increases in physical fitness are often associated with improvements in certain chronic diseases, such as hypertension and coronary heart disease. Recent evidence has shown that exercise also influences the neuroendocrine and immune systems, resulting in a potential to benefit those with chronic immunodeficiency diseases. Therefore, exercise may prove to have a profound impact on the management of the acquired immunodeficiency syndrome (AIDS). Our current work includes the investigation of the immunologic and stress-attenuating effects of an aerobic exercise training program for individuals at risk for AIDS. Upon completion of training, the subjects showed a significant increase in helper/inducer (CD4) cells and the inducer subset (CD45RA+CD4+) which activate suppressor/cytotoxic (CD8) cells. These increases, which average about 50 cells per cubic millimeter, are comparable to those observed in some studies of the AIDS drug comparable to those observed in some studies of the AIDS drug azidothymidine (AZT), but without the accompanying side effects. Also, individuals undergoing aerobic training reported no increases in anxiety and depression in response to notification of a positive HIV-1 serologic status. These findings taken together indicate that an aerobic exercise training program may enhance certain critical components of cellular immunity as well as acting as a buffer for the detrimental mood changes that typically accompany stress, thus providing a timely, promising behavioral approach to helping HIV-1-infected individuals.

Surrogate Markers of Disease Studied as Means of Determining AIDS Drugs' Effectiveness

ENOUGH EVIDENCE may exist to approve two analogues of zidovudine ([AZT] Retrovir, Burroughs Wellcome, Research Triangle Park, NC). At issue is whether surrogate markers of disease progression, like CD4 cell counts, can substitute for clinical end points like death. If so, data from ongoing trials might be collated into a convincing case. If not, it could be 2 years or more before traditional criteria are met. The drugs ddC (dideoxycytidine, Hoffmann-LaRoche Inc, Nutley, NJ) and ddI (didanosine [formerly called dideoxyinosine], Bristol-Myers Squibb Company, Princeton, NJ) inhibit viral replication as does zidovudine, which is still the only licensed drug that fights the human immunodeficiency virus (HIV) linked with the acquired immunodeficiency syndrome (AIDS). "Preliminary data show clear-cut drug activity," says Margaret Fischl, MD, who studies all three drugs as an investigator for the National Institutes of Health (Bethesda, Md) AIDS Clinical Trials Group. All three can cause peripheral neuropathy. But ddI

Wider Access Provided to AIDS Drugs With Actions Against HIV, CMV Infections

PHYSICIANS NOW HAVE broader access to two more treatments for patients who have acquired immunodeficiency syndrome (AIDS). Dideoxycytidine (ddC, Hoffmann-LaRoche, Nutley, NJ) is being offered to patients who cannot take zidovudine (AZT, Burroughs Wellcome, Research Triangle Park, NC), the only approved drug that fights the human immunodeficiency virus (HIV) linked to AIDS. Foscarnet (trisodium phosphonoformate, Astra Pharmaceuticals, Westborough, Mass) is available for patients who cannot take ganciclovir (Cytovene, Syntex, Humacao, PR) the sole treatment for cytomegalovirus. Foscarnet is also being offered to patients who have acyclovir-resistent herpes. Its main side effect is renal toxicity. Ganciclovir can induce neutropenia, and both zidovudine and ganciclovir suppress bone marrow, to the extent that one is a contraindication for the other in patients who have anemia. Both agents also tend to become ineffective after prolonged use. The drug ddC has been available to patients who cannot take zidovudine or dideoxyinosine (ddI, Bristol-Myers Squibb, New

Expanding AIDS Drug Availability

A FOOD AND DRUG Administration (FDA) committee has endorsed in principle the concept of expanding the availability of drugs at an early stage of testing to treat acquired immunodeficiency syndrome (AIDS). The driving forces behind this move include AIDS activist groups and support from such medical leaders as Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. In accepting the principle, the FDA committee nevertheless grappled with a long list of potential issues that had to be left for later resolution. The committee recommended that these issues be resolved by another group that will be mandated to oversee the process of getting the idea off the ground. Among these issues are the following: Even though drugs may be made available during phase I testing, it is necessary to ensure that properly controlled clinical trials to determine efficacy will not be compromised. Some evidence must exist that

AIDS Drug Development, Availability Intensify

RECENT ACTIONS by federal health officials deliver on promises made in Montreal at the Fifth International Conference on Acquired Immunodeficiency Syndrome (AIDS) to speed up development, clinical trials, and availability of drugs to combat human immunodeficiency virus (HIV) disease. A month ago, the Food and Drug Administration (FDA) approved for marketing ganciclovir, produced by Syntex Corporation, Palo Alto, Calif, which is used to treat cytomegalovirus retinitis. The agency also gave the status of "investigational new drug for treatment"—thus allowing expanded premarket distribution—to recombinant human erythropoietin used to treat AIDS-associated anemia, produced by Ortho Pharmaceutical Corporation, Raritan, NJ. Ortho has announced that the company will provide the drug free during testing to patients who are anemic either as a result of HIV infection or because of the effects of taking zidovudine, or AZT. Two weeks earlier, the FDA approved for marketing aerosolized pentamidine (made by Lyphomed Inc, Rosemont, Ill) as prophylaxis

Lymphadenopathy in a heterogeneous population at risk for the acquired immunodeficiency syndrome (AIDS)--a morphologic study.

The acquired immunodeficiency syndrome (AIDS) appears to be expanding both in the population at risk and in its clinical form of presentation. Persistent generalized lymphadenopathy has been reported in homosexual men who have immunologic abnormalities associated with AIDS. We are reporting ten cases of unexplained persistent generalized lymphadenopathy that have occurred in a heterogeneous population group at risk for AIDS (homosexual men, drug addicts, or Haitians). The morphologic findings of reactive follicular hyperplasia, increased interfollicular cellularity including an abundance of plasma cells and immunoblasts, preservation of the sinuses containing a sprinkling of polymorphonuclear leukocytes, and occasional multinucleated lymphoid cells constitute a constellation of features that are consistent enough so that AIDS should be included in the differential diagnosis.