PubMed Health⌕ Search

Biomedical subjects

Michael S Saag

Publications and source records attributed to Michael S Saag.

At least 19 recordsLinked to original sources
PubMed2006

Can routine clinical markers be used longitudinally to monitor antiretroviral therapy success in resource-limited settings?

Although routine clinical markers are used routinely to determine the stage of human immunodeficiency virus (HIV) disease, their use in monitoring response to antiretroviral therapy is poorly defined. Selected clinical markers were evaluated for their ability to predict first-line antiretroviral therapy success. No clinically meaningful variables were identified that predicted virologic or immunological success, implying that the CD4+ cell count and HIV type 1 RNA level data are required for optimal management of antiretroviral therapy.

Adult↗
PubMed2006

Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

CONTEXT: The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. OBJECTIVE: To report on the feasibility and early outcomes of the program. DESIGN, SETTING, AND PATIENTS: Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. INTERVENTION: Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. MAIN OUTCOME MEASURES: Survival, regimen failure rates, and CD4 cell response. RESULTS: We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. CONCLUSION: Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.

Adolescent↗
PubMed2006

Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel.

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

Adult↗
PubMed2006

Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: the results of AIDS Clinical Trials Group 5068.

BACKGROUND: The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment interruption (ATI). METHODS: Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. RESULTS: Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1,000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV vCP1452 did not affect viral load measures. CONCLUSIONS: In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated.

AIDS Vaccines↗
PubMed2006

Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients.

CONTEXT: Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. OBJECTIVE: To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily. SETTING: Twenty-six centers in the United States, Canada, and Puerto Rico. PATIENTS: A total of 171 antiretroviral naive HIV-infected individuals were enrolled in a 48-week, phase 3, open-label, randomized study. MAIN OUTCOME MEASURE: Proportion of patients with HIV-RNA levels < 50 copies/mL. The pharmacokinetic profile of saquinavir-SGC was analyzed in a subset of randomly selected patients. RESULTS: In the primary intent-to-treat population at week 48, 51% (38/75) and 71% (55/77) of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, achieved HIV-RNA suppression < 50 copies/mL (P = .5392, 95% 1-sided confidence interval [CI] = -33.5%). In the on-treatment (OT) population, 73% (38/52) and 93% (54/58) of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, had effective viral suppression < 50 copies/mL (P = .5015, 95% 1-sided CI = -33.4%). Mean CD4+ cell counts increased by 239 and 204 cells/microliters (mcL), in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, in the OT analysis (P = .058). Both regimens were reasonably well tolerated, although more gastrointestinal adverse events were reported with saquinavir-SGC/ritonavir. Pharmacokinetic profiles in 6 patients showed an observed median Cmin at 24 hours of 429 ng/mL (range, 68-1750 ng/mL). CONCLUSIONS: Once-daily efavirenz was statistically superior to once-daily saquinavir-SGC/ritonavir. Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study.

Adult↗
PubMed2006

Distribution of health care expenditures for HIV-infected patients.

BACKGROUND: Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy. METHODS: Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates. RESULTS: Among the 635 patients, total annual expenditures for patients with CD4+ cell counts <50 cells/microL (36,533 dollars per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts > or =350 cells/microL (13,885 dollars per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at approximately 10,500 dollars per patient per year across CD4+ cell count strata. Outpatient expenditures were 1558 dollars per patient per year; however, the clinic and physician component of these expenditures represented only 359 dollars per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%-84% of annual expenses). CONCLUSIONS: Physician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States.

Adolescent↗
PubMed2006

Sustained HIV viral suppression following treatment interruption: an observational study.

Treatment of HIV-infected patients with HAART can result in long-term suppression of viral loads to undetectable levels. Rapid virologic rebound typically follows treatment interruption (TI), with a potential for significant loss of CD4+ cells. Patients who maintain virologic suppression despite interrupting treatment have not been well described. All patients with a pretreatment viral load (VL) > or = 5000 copies/ml, who had been on therapy for > or = 2 weeks, and who underwent a TI lasting > or = 180 days were analyzed. Patients whose maximum VL did not exceed 5000 copies/ml > or = 6 months after starting TI ("nonrebounders") were compared with those whose VL exceeded 5000 copies/ml (rebounders). Seventy-one patients were included in the analysis. Nineteen (27%) were nonrebounders. Ninety-four percent of patients in each group interrupted treatment for reasons unrelated to virologic response. Median change in CD4 count during TI was not significantly different between the nonrebounder and rebounder groups (-20.5/microl vs. -64.0/microl; p < 0.086). In a multivariate logistic regression analysis, the following factors predicted nonrebounder status: peak VL before TI (log10 copies/ml) (OR = 0.14, 95% CI = 0.04-0.48, p = 0.0016); having received HAART (vs. mono/dual therapy) as initial regimen (OR: 11.0, 95% CI: 2.04-59.8, p = 0.0054); and female gender (OR = 4.8, 95% CI = 1.09-21.5, p = 0.0384). The large majority of chronically infected HIV patients with a TI > or = 180 days interrupted treatment for reasons unrelated to virologic response. Almost 30% did not have a significant virologic rebound. Those patients were more likely to be female, had a lower peak VL prior to treatment, and their initial regimen was more likely to be HAART. Examining the immune responses of nonrebounders may contribute to the understanding of protective immunity to HIV.

Adult↗
PubMed2005

Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus.

Emtricitabine (FTC) is a new nucleoside agent that has activity against both human immunodeficiency virus (HIV) and hepatitis B virus. It is very similar to lamivudine (3TC) with respect to its activity, convenience, and safety and resistance profile. Indeed, with the exception of the longer intracellular half-life of triphosphate FTC, there is little to distinguish between the 2 drugs. Clinical trials comparing FTC with 3TC as part of a triple-drug regimen have demonstrated their equivalence, whereas a study comparing activity of FTC with that of stavudine demonstrated FTC's superiority. In clinical practice, the choice of 3TC versus FTC will most likely be made in the context of drugs coformulated with them. Although FTC is not formally approved for use in patients coinfected with HIV and hepatitis B virus, it is often a preferred choice for such patients when combined with tenofovir, which also has anti-hepatitis B virus activity. Recent treatment guidelines for the treatment of HIV infection by both the International AIDS Society-USA and US Department of Health and Human Services have placed FTC in combination with tenofovir, didanosine, or zidovudine in the preferred category of nucleoside backbone regimens for patients receiving antiretroviral therapy.

Anti-Retroviral Agents↗
PubMed2005

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.

We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach.

Anti-HIV Agents↗
PubMed2005

Antigenic conservation and immunogenicity of the HIV coreceptor binding site.

Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies.

Amino Acid Sequence↗
PubMed2005

Unusual thromboses associated with protein S deficiency in patients with acquired immunodeficiency syndrome: case reports and review of the literature.

Recent reports indicate that patients infected with HIV are at increased risk for the development of thrombosis. Among other possibilities, an acquired deficiency of protein S (PS), one of the plasma's natural anticoagulants, might explain this tendency. PS deficiency can be classified in three types depending on the levels of total and free protein (antigenic assays) as well as anticoagulant activity (functional assay). Although the prevalence of inherited PS deficiency is not known because of its rarity, several conditions can lead to acquired forms of the disease. We report two AIDS patients with coexistent type III PS deficiency and thrombosis. Our first patient presented with bilateral chronic leg ulcers and a skin biopsy revealed dermal microthromboses. On laboratory evaluation he had PS deficiency and was started on anticoagulation, but was lost to follow-up. The second patient presented with hepatic vein thrombosis (Budd-Chiari syndrome) and was also PS deficient. On long-term anticoagulation, she experienced resolution of the thrombosis. Neither patient had prior personal or family history of venous thrombosis, nor acquired risk factors such as immobility, acute infection, recent surgery, or hormonal therapy. The literature contains a few reports of skin ulcers and Budd-Chiari syndrome associated with PS deficiency, although none in AIDS patients. While a larger number of studies describe an association between PS deficiency and HIV infection, the causal effect of this deficiency on the thrombophilic tendency in AIDS has not been established. We propose that awareness of the increased risk for thrombosis in HIV infection is important to the understanding of disease pathophysiology and management of these patients.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Sexually transmitted disease/HIV transmission risk behaviors and sexually transmitted disease prevalence among HIV-positive men receiving continuing care.

OBJECTIVE: HIV primary care clinics offer an environment in which to deliver prevention messages and to conduct sexually transmitted disease (STD) screening. Determination of the prevalence and factors associated with risk-taking behaviors among HIV clinic attendees is needed. GOAL: The goal of this study was to describe risk behaviors and STD prevalence in males receiving HIV primary care. STUDY: Participants underwent an interviewer-administered survey and STD testing during this cross-sectional study. RESULTS: Over two thirds of study participants reported sexual activity within the prior 6 months of which 6% were infected with gonorrhea or chlamydia. Men performing insertive rectal sex were 5 times less likely to use condoms when the partner was HIV-positive (odds ratio [OR], 5.14; 95% confidence interval [CI], 1.90-13.91), whereas patients with higher CD4 counts were more likely to engage in unprotected receptive rectal sex (OR, 1.20; 95% CI, 1.02-1.42). CONCLUSION: HIV primary care clinics provide access to patients in need of HIV prevention intervention and are appropriate sites for these activities.

Adult↗