Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults

Pai, Nitika Pant; Lawrence, Jody; Reingold, Arthur; Tulsky, Jacqueline P.

doi:10.1002/14651858.cd006148

Cited by 10 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential benefits of structured interruptions should be weighed against the risks, which include the development of HIV-related illnesses and viral resistance. A recent meta-analysis confirmed all these findings, showing evidence of harm in patients with relatively advanced HIV disease, and concluding that structured treatment interruptions were not presently recommended [9].…”

Section: Discussionmentioning

confidence: 84%

“…Studies have shown that structured interruptions of treatment significantly increased the risk of opportunistic disease or death from any cause for persons infected with HIV [8,9], but there are few studies focusing on pregnant women. The clinical implications of treatment discontinuation after delivery have not been established in the era of potent ARVs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Predictors of postpartum viral load rebound in a cohort of HIV‐infected Brazilian women

Cavallo

Kakehasi

Andrade

et al. 2009

Intl J Gynecology & Obste

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Predictors of postpartum viral load rebound in a cohort of HIV‐infected Brazilian women

Cavallo

Kakehasi

Andrade

et al. 2009

Intl J Gynecology & Obste

View full text Add to dashboard Cite

show abstract

“…Although it has been opined that the viral rebound during structured cART interruption is not harmful, this has been contradicted by the SMART study which demonstrated an increased incidence of opportunistic infection and death in persons who underwent structured treatment interruption compared to those who did not, while not decreasing the adverse effects of antiretroviral therapy (68,81,82); however, these and similar studies focused primarily on viral rebound and subsequent viral suppression after cART reinitiation (83). Within this cohort, numerous treatment interruptions, although due to patient adherence and not medically controlled, were recorded and may have contributed to the wide range of subsequent pathologies.…”

Section: Discussionmentioning

confidence: 99%

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

Lamers¹,

Rose²,

Maidji

et al. 2016

J Virol

138

125

View full text Add to dashboard Cite

HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV ؉ ) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. IMPORTANCEIt is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, "Where is HIV hiding?" A well-studied HIV reservoir is "resting" T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV ؉ participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissueassociated HIV is present despite cART and can inform future studies into HIV persistence.

show abstract

“…Studies in other population groups that investigated interruptions as therapeutic alternatives to continuous therapy such as intentional treatment holidays and unintentional interruptions have found harmful results. Initial concerns about long-term safety and reports of a lack of improved virological response in trials of structured interruptions [32,33] were confirmed by the Strategies for Management of Antiretroviral Therapy (SMART) study, which found that CD4-guided episodic therapy increases the risk of opportunistic disease or death in relation to continuous treatment [34]. A review of unstructured TIs found an increased risk of opportunistic infections, virological failure, drug resistance, poor immunological recovery and death [35].…”

Section: Discussionmentioning

confidence: 99%

Adherence to antiretroviral therapy and treatment outcomes among conflict-affected and forcibly displaced populations: a systematic review

et al. 2012

View full text Add to dashboard Cite

BackgroundOptimal adherence to highly active antiretroviral therapy (HAART) is required to promote viral suppression and to prevent disease progression and mortality. Forcibly displaced and conflict-affected populations may face challenges succeeding on HAART. We performed a systematic review of the literature on adherence to HAART and treatment outcomes in these groups, including refugees and internally-displaced persons (IDPs), assessed the quality of the evidence and suggest a future research program.MethodsMedline, Embase, and Global Health databases for 1995–2011 were searched using the Ovid platform. A backward citation review of subsequent work that had cited the Ovid results was performed using the Web of Science database. ReliefWeb and Médecins Sans Frontières (MSF) websites were searched for additional grey literature.Results and conclusionWe screened 297 records and identified 17 reports covering 15 quantitative and two qualitative studies from 13 countries. Three-quarters (11/15) of the quantitative studies were retrospective studies based on chart review; five studies included <100 clients. Adherence or treatment outcomes were reported in resettled refugees, conflict-affected persons, internally-displaced persons (IDPs), and combinations of refugees, IDPs and other foreign-born persons. The reviewed reports showed promise for conflict-affected and forcibly-displaced populations; the range of optimal adherence prevalence reported was 87–99.5%. Treatment outcomes, measured using virological, immunological and mortality estimates, were good in relation to non-affected groups. Given the diversity of settings where forcibly-displaced and conflict-affected persons access ART, further studies on adherence and treatment outcomes are needed to support scale-up and provide evidence-based justifications for inclusion of these vulnerable groups in national treatment plans. Future studies and program evaluations should focus on systematic monitoring of adherence and treatment interruptions by using facility-based pharmacy records, understanding threats to optimal adherence and timely linkage to care throughout the displacement cycle, and testing interventions designed to support adherence and treatment outcomes in these settings.

show abstract

Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults

Cited by 10 publications

References 65 publications

Predictors of postpartum viral load rebound in a cohort of HIV‐infected Brazilian women

Predictors of postpartum viral load rebound in a cohort of HIV‐infected Brazilian women

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

Adherence to antiretroviral therapy and treatment outcomes among conflict-affected and forcibly displaced populations: a systematic review

Contact Info

Product

Resources

About