Providing Universal Access While Avoiding Antiretroviral Resistance: Ethical Tensions in HIV Treatment

The provision of effective antiretroviral therapy is an ethical imperative, and global access to antiretroviral drugs is an important aspect of this. The other less recognised aspect of effective HIV management is in ensuring that HIV does not become resistant to the drugs used in treatment (and increasingly also in prevention), as multi-drug resistant HIV poses a major threat to the sustainability of current responses to HIV control. In resource-constrained environments, the rapid scale up of access to life-saving anti-HIV treatment was achieved using a public health approach that standardised antiretroviral regimens, minimised laboratory monitoring, and devolved responsibilities from clinicians where necessary. In recent years demand for antiretroviral treatment has increased due to new understandings of the clinical importance of early treatment, but global investment has declined. Exponential growth of the population using antiretrovirals without careful monitoring increases the risk of significant antiretroviral drug resistance. In this chapter, I consider the example of single-drug interventions to prevent parent-to-child HIV transmission, and how the implementation of that strategy increased health risks for mothers. I argue that while global antiretroviral scale up must continue, laboratory monitoring at individual and national levels needs to improve to maintain treatment effectiveness, and protocols for moving people from failing regimens need to be strengthened

Effect Estimates in Randomized Trials and Observational Studies:Comparing Apples With Apples

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration

Cognitive and Neurologic Rehabilitation Strategies for Central Nervous System HIV Infection

PURPOSE OF REVIEW: Cognitive impairment leading to disability is increasingly seen in people living with human immunodeficiency virus (PLWH). Rehabilitation can alleviate the effects of cognitive impairment upon function. The aim of this paper is to discuss the strategies that have been used in cognitive and neurologic rehabilitation in PLWH. RECENT FINDINGS: Studies examining pharmacological and non-pharmacological strategies were analysed. Medical management of HIV and co-morbidities should be optimised. Non-pharmacological strategies, including nerve stimulation techniques, exercise-based interventions, and paper and computer-based cognitive rehabilitation, have some evidence supporting their use in PLWH either as stand-alone interventions or as part of a multidisciplinary approach. Both pharmacological and non-pharmacological rehabilitation strategies have been used with PLWH. More intervention trials are needed to assess cognitive and neurological rehabilitation strategies and further evaluate their potential benefit in PLWH

Expert consensus statement on the science of HIV in the context of criminal law.

CAPRISA, 2018.Abstract available in pdf

The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial : a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

Background Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain. Objective To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial. Design Open-label, parallel-group, randomised controlled trial. Setting Forty-three HIV clinical centres in the UK NHS. Participants HIV-positive adults taking standard combination ART with a suppressed VL for ≥ 6 months. Interventions Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound. Main outcome measures The primary outcome was reduction of future drug options, defined as new intermediate-/high-level resistance to one or more drugs to which the patient’s virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis. Results In total, 587 participants were randomised (77% male, 68% white) to OT (n = 291) or PI-mono (n = 296) and followed for a median of 44 months, of whom 2.7% withdrew/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan–Meier estimate 3.2%) in the OT group and 95 patients (35.0%) in the PI-mono group [absolute risk difference 31.8%, 95% confidence interval (CI) 24.6% to 39.0%; p < 0.001]. PI-mono patients who changed to ART after VL rebound all resuppressed (median 3.5 weeks). The proportions with loss of a future drug option at 3 years were 0.7% in the OT group and 2.1% in the PI-mono group (difference 1.4%, (95% CI –0.4% to 3.4%); non-inferiority demonstrated). There were no significant differences in serious disease complications between groups or in the frequency of grade 3 or 4 clinical AEs (16.8% OT group vs. 22% PI-mono group; absolute risk difference 5.1%, 95% CI –1.3% to 11.5%; p = 0.12). Overall, the PI-mono strategy was shown to be cost-effective compared with OT under most scenarios explored. PI-mono was cost saving because of the large savings in ART drug costs while being no less effective in terms of quality-adjusted life-years in the within-trial analysis and only marginally less effective when extrapolated to lifetime outcomes. Conclusions PI monotherapy, with prompt reintroduction of combination therapy for VL rebound, was non-inferior to combination therapy in preserving future treatment options and is an acceptable and cost-effective alternative for long-term management of HIV infection. Trial registration Current Controlled Trials ISRCTN04857074. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 21. See the NIHR Journals Library website for further project information

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

Presentes no The INSIGHT START Study Group: Beatriz Grinsztejn; Valdiléa Veloso; Sandra Wagner Cardoso (Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil)Submitted by Fábio Marques ([email protected]) on 2018-10-15T14:21:48Z No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-10-17T13:47:56Z (GMT) No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5)Made available in DSpace on 2018-10-17T13:47:57Z (GMT). No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5) Previous issue date: 2015Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter