Available HIV drugs fall into three classes: nucleosides (nukes), non-nukes and protease inhibitors (PIs). Cross-resistance can occur, making all the drugs in a particular class ineffective for an individual. Therefore, doctors are choosing to use the fewest drugs possible for early treatment, saving other drugs for later therapy. Short-term results of triple therapy with three nukes (AZT, 3TC, and ABC (abacavir)) have been promising, especially among patients with little prior exposure to antiretroviral drugs. Thus some doctors are using triple nuke therapy in recently infected patients, and others with high CD4+ counts and low viral loads.
The advent of combined antiretroviral therapy (ART) in the past decade has led to HIV suppression in most cases. Virological failure was the main reason for ART switch a few years ago; however, toxicity and treatment simplification have now gained importance due to the availability of more effective and convenient drugs. This study assessed the reasons for ART switch in daily practice. Observational retrospective study that included patients whose ART was switched between January 2011 and July 2012. Patients with any other switch during the follow-up period (until September 2013) were excluded. A total of 246 patients were included. Main reasons for ART switch were simplification (33%) and toxicity (31%), followed by clinical trial inclusion (13%), virological failure (6%), drug interaction (4%), patient decision (3%), lack of adherence (2%), pregnancy (1%) and other (8%). Eighty patients switched to a simpler regimen (median age 48 [40-53], mean CD4 count 608±265 cells/cl, 89% <50 copies/ml, mean number of previous regimens 6±5, mean time on previous ART 3±2 years). In this case, previous ART mostly included 2NRTI+1PI/r (54%) (Figure 1). The simplification strategy mainly contained nuke-sparing regimens (60%) based on PI (DRV/r 48%): monotherapy 46%, dual therapy 13% (PI/r+maraviroc 9%, PI/r+NNRTI 4%) and triple therapy 1% (PI/r+maraviroc+raltegravir). The second preferred simplification option was 2NRTI+1NNRTI (24%). Seventy-seven patients switched due to toxicities (median age 47 [43-53], mean CD4 count 606±350 cells/μl, <50 copies/ml 82%, mean number of previous regimens 4±3, mean time on previous ART 3±3 years). Renal (25%) and CNS (18%) toxicities were the main reasons for ART switch, followed by diarrhoea (16%), liver enzyme elevation (ALT 10%; AST 9%; bilirubin 7%), lipid elevation (cholesterol 5%; triglycerides 8%), nausea (7%) and other (=5%) (Figure 2). All patients with renal toxicity were under TDF and in most cases this drug was removed from the new regimen (with 3TC/ABC or nuke-sparing). Among patients with CNS toxicity, 79% were taking EFV; the main new treatment was a second-generation NNRTI (ETR)+2NRTI. Toxicities were completely resolved in 66% of patients, partially resolved in 22% and not resolved in only 12%; the median time from ART switch to toxicity resolution was 4 (2-8) months. The main reasons for ART switch in daily practice are simplification and toxicities, renal and CNS toxicities being the most prevalent. The preferred simplification strategies are nuke-sparing regimens, mainly DRV/r-based monotherapy and dual therapy. ART switch leads to a complete resolution of toxicities in most cases in the short term.
With the efficacy of antiretroviral therapy already guaranteed for all practical purposes, the main objective in the management of HIV-positive patients has moved to reduce and prevent potential long-term toxicities. Nucleos(t)ide-sparing regimens could enable the best to address this issue, with a wide range of current options that may allow adaptation to distinct patient populations. Monotherapy with boosted darunavir and lopinavir has been safely prescribed as maintenance therapy to stable patients on stable antiretroviral therapy without nadir CD4 count < 200/mm³, low-level baseline viremia, prolonged viral suppression, and without prior virologic failure. In the presence of all these requirements, dual therapy with lamivudine plus boosted lopinavir or atazanavir has been shown to be equivalent to standard triple therapy. Other nucleoside-sparing dual therapies, especially using raltegravir combined with boosted darunavir or lopinavir and etravirine or rilpivirine in combination with boosted darunavir, have performed well as simplification strategies or rescue interventions in a wide spectrum of patients as long as drug resistance was absent. With current economical constrains, nuke-sparing regimens have attained a degree of maturity that makes it possible to anticipate that they will play an important role in the optimization of antiretroviral therapy in the near future.
Another regimen consisting only of nucleoside-analog drugs has shown unsatisfactory suppression of HIV.
A CME (continuing medical education) module for physicians explains the problem with two antiretroviral regimens that failed last year. Several possible causes for the failure had been proposed. Now it appears that the problem was too low a genetic barrier to HIV developing certain resistance mutations.
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The objectives of this study were to reduce the cytotoxic effect of nevirapine (NVP) and to enhance its anti-HIV efficacy through mesoporous silica nanoparticles (MSNPs) mediated delivery. MSNPs were synthesized and characterized by various techniques. Confocal microscopy and flow cytometry results exhibited efficient uptake of FITC-conjugated MSNPs in TZM-bl cells. The NVP was loaded within MSNPs, and its anti-HIV1 efficacy was assessed on HIV1 (R5 and X4 variants) infected TZM-bl cells and further confirmed on peripheral blood mononuclear cells (PBMCs). The in vitro assessment of the anti-HIV1 potential of NVP and NVP-MSNPs in HIV1 infected TZM-bl cells and PBMCs showed increased efficacy of NVP upon loading within MSNPs with significant increase in therapeutic index. The increased efficacy against HIV1 was accompanied by reduced cytotoxicity to TZM-bl cells and PBMCs. Further, reverse transcriptase (RT) assay confirmed the inhibitory effect on RTase, which is a key enzyme in HIV-1 replication. The present study showed that entrapment of NVP within MSNPs led to an increased efficacy with reduced cytotoxic effect resulting in the enhanced therapeutic index (TI).
A significant proportion of under-five diarrhea-related morbidity and mortality can be reduced by timely initiation of treatment. This study assessed determinants of timely treatment-seeking behavior for diarrheal disease among caregivers with under-five children in public hospitals in Sidama region, Ethiopia. A facility-based unmatched case-control study was conducted among public hospitals. Data were collected using KOBO Collect with a smartphone and analyzed using SPSS 26. Three hundred two cases and 302 controls were included. Being urban resident (AOR = 0.251 (95% CI, 0.157, 0.401, p = 0.000)), mothers with no formal education (AOR = 0.397 (95% CI, 0.222, 0.713, p = 0.002)), child age < 24 months (AOR = 0.210 (95% CI, 0.121, 0.364, p = 0.000)), above 120 min walking distance from nearby health facility [AOR = 0.426 (95% CI, 0.211, 0.861, p = 0.017)] were negatively associated. Whereas, reported cost of treatment easy to pay (AOR = 7.988 (95% CI, 3.734, 17.091, p = 0.000)), community-based health insurance (CBHI) membership (AOR = 4.940 (95% CI, 3.124, 7.812, p = 0.000)), and a history of previous diarrhea (AOR = 1.702 (95% CI, 1.021, 2.837, p = 0.041)) were positively associated with timely treatment seeking behavior. Being urban residents, caregivers' educational status, child age <24 months, and long walking distance from nearby health facility, low-cost of treatment, being a CBHI member, and a child with a history of previous diarrhea were independently associated with timely treatment-seeking. Therefore, it is important to design strategies to improve these factors by involving relevant stakeholders. Future researchers should consider strong designs like prospective cohort involving multiple health facilities to identify causal factors for timely treatment-seeking behavior.
Recent work has called into question the ability of visual acuity (VA) to accurately represent changes in visual function in infantile nystagmus (IN). This systematic review investigated factors affecting visual performance in IN, to guide development of suitable alternatives to VA. Included studies used an experimental manipulation to assess changes in visual function in people with IN. Interventional studies, case series and case studies were excluded. Six databases were searched in August 2023. Selection, detection, attrition and measurement bias were assessed. Due to heterogeneous methodologies, narrative synthesis was undertaken. Eighteen relevant papers were identified, 11 of which complied with the review criteria. Articles were grouped according to the factor manipulated to evoke within-participant changes in performance (motion blur, psychological state, gaze angle or visual crowding). Optotype, image, grating and moving stimuli have been employed under varying lighting conditions and exposure duration. Several factors affecting visual performance should be considered when assessing visual function in IN. While maximum VA is a useful metric, its measurement deliberately minimises nystagmus-specific factors such as changes in visual performance with gaze angle and the 'slow to see' phenomenon. Maximum VA can be measured using the null zone, providing unlimited viewing time, reducing stress/mental load and minimising visual crowding. Gaze-dependent functional vision space is a promising measure which quantifies the impact of the null zone but does not consider temporal vision. Although no complete measurement technique has yet been proven, this review provides insights to guide future work towards development of appropriate methods.
To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 μL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 μL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves.