DISCUSSION
gastrointestinal symptoms, fibrosis, coinfection, mitochondrial dysfunction, cognitive impairment, toxicity, inflammation, immunologic failure, intestinal barrier impairments, AIDS, bloating, gastrointestinal infections, fatigue, diarrhea, anemia, granulocytopenia, infection, HIV.Gastrointestinal complications, nausea, vomiting, neutropenia
MUSCLE WEAKNESS, VIRUS, GASTROINTESTINAL INFECTIONS, NEUTROPENIA, ADVERSE EVENTS, INFLAMMATION, AIDS, FIBROSIS, COMPLICATION, ANEMIA, GRANULOCYTOPENIA, INFECTION, INFLAMMATIONS, PANCYTOPENIA, DELETION, CHRONIC INFLAMMATION, MITOCHONDRIAL DYSFUNCTION, COMPLICATIONS
The intestinal microbiota plays an essential role in stimulating the development and maintenance of the intestinal immune system.HIV studies showed that HIV can wreak havoc in the gut, where there are many CD4 cells, This happens fairly soon after infection with HIV.Gastrointestinal complications are common in people living with HIV, including intestinal barrier impairments, mitochondrial dysfunction, and alterations in the microbiota. These complications are thought to be caused by chronic inflammation, immune activation, and the use of ART.Intestinal barrier impairment refers to the loss of integrity of the intestinal mucosa, which can lead to increased permeability and transfer of contaminants from the intestine into the bloodstream. This can trigger immune activation and inflammation, which can further damage the intestinal barrier and exacerbate the problem.Mitochondrial dysfunction is a common complication of PLWH and is associated with consumption of ART. Mitochondria are responsible for energy production in cells, and when they are dysfunctional, cells cannot produce enough energy to function properly. This can lead to a range of symptoms, including fatigue, muscle weakness, and cognitive impairment.In addition, modern antiretroviral drugs, although well tolerated, cause severe gastrointestinal symptoms such as nausea, vomiting, bloating, or diarrhea in mild to severe forms.Previous studies demonstrated that Yoghurt enrichment with probiotics as a snack may increase CD4 levels and protect against some HIV‐related gastrointestinal infections and local inflammations.This local inflammation can lead to new collagen formation and fibrosis, which contribute to the deletion of CD4After the HIV virus infects the CD4 cells, it plants itself in several organs, including the MALT system of the digestive system. In this organ, the HIV implants itself in up to 10 times the amount than in the bloodstream.At this stage, the virus begins to mix its genome with that of the intestinal lymphoid cells. Treatment with ART can combat the virus before this fusion, but after genetic fusion and entry into the silent phase, the virus is inaccessible to the immune system and antivirals.Probiotics with their effect on enteric translocations bring these infected cells out of their silent phase and expose them to the immune system and pharmacological agents, thereby reducing the burden on the infected reservoir.In addition to restoring the balance of the gut microbiota in terms of competition with pathogens and improving the intestinal barrier, probiotics also play an important role in restoring mucosal immune function through the Th17/Treg ratio, which reduces systemic and local inflammation in the gut.Probiotics also may promote epithelial healing by altering intestinal flora and reduce the risk of viral transmission and hospitalization for coinfection by preventing the decline in CD4So in this study, we administered a kind of probiotics with a high count of lactobacilli then this intervention can lead to reducing inflammation in intestinal mucosa and make a good response for HIV patients with immunologic failure.Our results show that the administration of probiotics increased CD4 cell counts compared with the placebo. After discontinuation of probiotics, CD4 counts approached baseline values again but were still significantly higher.Probiotic administration resulted in an average increase of 62 and 49 CD4 cells/μL in both groups, respectively.our study showed that the number of CD4On the other hand, previous studies showed that a CD4 count of <50 cells/mmTherefore longer period probiotic intervention in this group of study can help them to overcome immunologic failure in persistent CD4 counts above 100 cells/mmIt is also recommended to consider other Reasons cited for immunologic failure including the role of the thymus gland, which declines with age, and drug toxicity of zidovudine, which clinically causes anemia, neutropenia, pancytopenia, and granulocytopenia in 45% of recipients of this drug.In this type of failure, it is also recommended to first rule out other causes of immunosuppression, such as HIV2, HTLV1, HTLV2, and drug toxicity, and the combination of didanosine and tenofovir is also among the causes that lead to a decrease in CD4 increase and a lack of appropriate immunological response.In our study, we excluded all the mentioned causes of immunologic failure.In another study by Livia Trois, conducted on 77 HIV‐infected children aged 2–12 years, they were divided into two groups: one group received probiotics containing In a similar study from Tanzania after the initiation of yogurt‐enriched probiotic consumption, an additional increase of 0.28 cells/μL/day (95% CI: 0.10–0.46, Notwithstanding the aforementioned studies, the pilot clinical trial ACTG 5350 aimed to investigate the potential of targeting the gut microbiota of vertically HIV‐infected children to reduce inflammation and immune activation. In the study, a probiotic preparation supplement containing No significant differences were observed when comparing the changes in CD4The small sample size is an important limitation in our study, but we tried to solve this important problem with the cross‐over study design.the main reason for this limitation was that only 13.59% of all HIV patients have immunological discordance, but this group was the best choice to study the effect of probiotics in HIV patients.Compared with previous studies, the patients we studied suffer from immunologic failure, and given the low CD4 count of the patients in our study, most are classified as stages 3 and 4 of AIDS. This shows the importance of CD4 count, as their low levels can cause numerous clinical adverse events and increasing CD4 count can significantly improve a patient's quality of life (Figure Patients' intervention tree diagram.We also propose to compare the effect of probiotics with new medications such as pidotimod. Pidotimod is an immunomodulatory drug that has been studied for its potential to improve immune function in HIV‐infected individuals and may be able to increase CD4