Discussion :
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 apparently happens fairly soon after infection with HIV.[6]
In addition, modern antiretroviral drugs, although well tolerated, cause severe gastrointestinal symptoms such as nausea, vomiting, bloating, or diarrhea in mild to severe forms.[7]
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 CD4+ T cells and limit the recovery of the immune response. An increased predisposition to collagen neogenesis may be related to a decreased population of virgin CD4+ T lymphocytes whose phenotype is not activated before antiretroviral therapy. Fibrosis may be one of the causes of failure of immune recovery during treatment despite suppressed viral replication.[8]
After 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 ten 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 .[9]
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 CD4+ cell count. ART -treated patients who do not show an immunological response (CD4 < 200) have lower lactobacilli levels, increased LPS and sCD14 levels, and increased inflammatory markers such as IL -6 and sCD14.[10]
So in this study we administered kind of probiotics with 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 administration of probiotics increased CD4 cell counts compared with 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 per microliter in both groups, respectively.
our study showed that the number of CD4+ cells increases by taking probiotics but decreases back to baseline levels after stopping probiotics. The results could also mean that by administering probiotics for a longer time, we could expose more infected cells and achieve a better result.
On the other hand previous studies showed that a CD4 count of < 50 cells/mm3 was a main predictor of treatment failure. This finding may be due to the fact that patients with baseline CD4 counts of ≤100 cells/mm3 have reduced immunity and response to initial treatment ART may be unsatisfactory . [3]
Therefore longer period probiotic intervention in this group of study can help them to overcome immunologic failure in persistent CD4 counts above 100 cells/mm3 .
It is also recommended to consider other Reasons cited for immunologic failure include 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. [11]
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.[12]
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 Bifidobacterium bifidum with Streptococcus thermophilus 2.5 x 10(10) CFU for two months, and the other group received a standard diet (control group). CD4 counts were collected at baseline and at the end of the study. The mean CD4 count increased in the probiotic group (791 cells/mm3), whereas it decreased slightly in the control group (538 cells/mm3). The change in mean CD4 cell count from baseline was +118 cells/mm3 versus -42 cells/mm3 in the children receiving the probiotic diet and the control group, respectively (p = 0.049).