Mechanisms of Virologic Failure in Previously Untreated HIV-Infected Patients From a Trial of Induction-Maintenance Therapy

Descamps, Diane

doi:10.1001/jama.283.2.205

Cited by 348 publications

(192 citation statements)

References 16 publications

Supporting

Mentioning

171

Contrasting

Unclassified

Order By: Relevance

“…Yet, not just any medicinal treatment simplification will do; the alleviation of triplecombination therapy with 2 drugs as maintenance therapy, 7 days per week, once failed radically (65)(66)(67)(68), and ritonavirboosted PI monotherapies, 7 days per week, have yet to match (45-48) current triple combination standards virologically (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Treatment Outcomes Following Viral Escapesmentioning

confidence: 99%

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

et al. 2015

View full text Add to dashboard Cite

Short, intraweekly cycles of anti‐HIV combinations have provided intermittent, effective therapy (on 48 patients) (1). The concept is now extended to 94 patients on treatment, 4 days per week or less, over a median of 2.7 discontinuous treatment years per patient. On suppressive combinations, 94 patients volunteered to treatment, 5 and 4 days per week, or reduced stepwise to 4,3,2, and 1 days per week in 94, 84, 66, and 12 patients, respectively, on various triple, standard, antiviral combinations, or nonregistered, quadruple, antiviral combinations. Ninety‐four patients on treatment 4 days per week aggregated 165 intermittent treatment years; no viral breakthrough was observed over 87 average treatment weeks per patient, 63 of 94 having passed 2.5 intermittent treatment years on any of the antiviral combinations prescribed. On the hyperintermittent treatment of 3, 2, and 1 days per week, HIV RNA surged >50 copies, 4 weeks apart, in 18 instances (6.8 viral escapes/100 hyperdiscontinuous maintenance years). Viral escapes could have been a result of erratic adherence (EA) to regimen or follow‐up (3 patients)—drug taken at half of the daily recommended dosage (8 patients) and/or overlooked archival‐resistant HIVs from antecedent treatment failures (6 patients). Aside from the above circumstances, HIV unexpectedly rebounded in 3 patients on 2 days per week treatment and 1 patient on 1 day per week treatment, posting 2.2 intrinsic viral escapes/100 highly discontinuous treatment years. All 18 escapes were eventually reversed by 7 days per week salvage combinations, and 11 of 18 patients have been back for a second course of intermittent therapy, 4 days per week or less. Both cell‐activation markers on the surface of T lymphocytes and cell‐bound HIV DNA levels remained stable or declined. CD4/CD8 ratios rose to ≤1 in 35% of patients, whereas CD4 counts went ≤500/μl in 75%. These values were previously 7 and 40%, respectively, on 7 days per week therapy. In our aging, long, HIV‐enduring, multitreated patient cohort, treatment 4 days per week and less over 421 intermittent treatment years reduced prescription medicines by 60%—equivalent to 3 drug‐free/3 virus‐free remission year per patient—actually sparing €3 million on just 94 patients at the cost of 2.2 intrinsic viral failure/100 hyperintermittent treatment years. At no risk of viral escape, maintenance therapy, 4 days per week, would quasiuniversally offer 40% cuts off of current overprescriptions.—Leibowitch, J., Mathez, D., de Truchis, P., Ledu, D., Melchior, J. C., Carcelain, G., Izopet, J., Perronne, C., David, J. R. Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project. FASEB J. 29, 2223‐2234 (2015). http://www.fasebj.org

show abstract

Section: Treatment Outcomes Following Viral Escapesmentioning

confidence: 99%

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Not all patients who initiate antiretroviral therapy r e s p o n d . T h e l a c k o f c l i n i c a l r e s p o n s e i s l i k e l y e x p l a i n e d b y p r o b l e m s w i t h a d h e r e n c e , suboptimal antiretroviral treatment potency, and genetic mutation of HIV strains (Descamps et al, 2000). Many patients experience substantial side effects, and it is not uncommon for changes to be made in antiretroviral regimens because of such side effects.…”

Section: Treatment Of Hiv Infectionmentioning

confidence: 99%

Neuropsychiatric Manifestations of HIV Infection and AIDS

Olisah¹

2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

View full text Add to dashboard Cite

“…5 Inadequate suppression of HIV RNA replication by HAART can result from several problems, including 1) low potency of the antiviral regimen, 2) viral resistance, 3) inadequate drug exposure, and 4) poor adherence to therapy. 6 Nonadherence is a leading cause of treatment failure. [7][8][9] Incomplete suppression of HIV RNA replication in the presence of antiretroviral medications can select for resistant strains of virus, compromising future therapeutic regimens.…”

Section: H Ighly Active Antiretroviral Therapy (Haart)mentioning

confidence: 99%

Nonadherence With Pediatric Human Immunodeficiency Virus Therapy as Medical Neglect

Roberts¹,

Wheeler

Tucker

et al. 2004

Pediatrics

View full text Add to dashboard Cite

ABSTRACT. Objective. To examine the results of an interventionist approach applied to human immunodeficiency virus (HIV)-infected children for whom caregiver nonadherence was suspected as the cause of treatment failure.Methods. The medical records of a cohort of 16 perinatally HIV-infected children whose care was managed at the Arkansas Children's Hospital Pediatric HIV Clinic for an uninterrupted period of >3 years were reviewed through July 2003. Data collected included date of birth, dates of and explanations for clinic visits and hospitalizations, dates of laboratory evaluations, CD4 ؉ T cell percentages, plasma HIV-1 RNA levels, antiretroviral medications, viral resistance tests (eg, phenotype and genotype), and physician-initiated interventions to enhance adherence to the medication regimen. A stepwise interventionist approach was undertaken when patients continued to demonstrate high viral loads, despite documented viral sensitivity to the medication regimen and caregivers' insistence that medications were being administered regularly.Step 1 was prescribing a home health nurse referral, step 2 was administering directly observed therapy (DOT) while the patient was hospitalized for 4 days, and step 3 was submitting a physicianinitiated medical neglect report to the Arkansas Department of Human Services.Results. The results for 6 patients for whom this stepwise approach was initiated are reported. Home health nurse referrals failed to result in sustained improvements in adherence in all 6 cases. Viral load assays performed before and after DOT provided an objective measure of the effect of adherence, with 12 hospitalizations resulting in a mean ؎ SD decrease in HIV RNA levels of 1.09 ؎ 0.5 log 10 copies per mL, with a range of 0.6 to 2.1 log 10 copies per mL. Four families responded to DOT hospitalization, and sustained decreases in the respective patients' viral loads were noted. In 2 cases, medical neglect reports were submitted when DOT did not result in improved adherence. These patients were eventually placed in foster care, with subsequent improvements in their viral loads and CD4 ؉ T cell percentages.Conclusions. Nonadherence with antiretroviral therapy can be established on the basis of persistently elevated HIV RNA levels that decrease with DOT. Nonadherence poses a danger to the child that is grave and potentially irreversible. Caregivers should be offered all available resources to help them adhere to a sound treatment plan. In cases of demonstrated inability to provide needed care, it is necessary to consider seeking child protection, even for apparently healthy children. Pediatrics 2004;114:e346 -e353. URL: http://www.pediatrics.org/ cgi/content/full/114/3/e346; adherence, HIV, pediatric, neglect.

show abstract

Mechanisms of Virologic Failure in Previously Untreated HIV-Infected Patients From a Trial of Induction-Maintenance Therapy

Abstract: During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.

Cited by 348 publications

References 16 publications

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

Neuropsychiatric Manifestations of HIV Infection and AIDS

Nonadherence With Pediatric Human Immunodeficiency Virus Therapy as Medical Neglect

Contact Info

Product

Resources

About