Different Degrees of Immune Recovery Using Antiretroviral Regimens with Vonavir or Zidovudine/Lamivudine/Efavirenz in HIVPositive Patients Receiving First Line Treatment in Iran.

BACKGROUND: The initial antiretroviral therapy (ART) regimens recommended by most national treatment guidelines in resource-limited settings consist of two Nucleoside Reverse-Transcriptase Inhibitors (NRTIs) and one Non-Nucleoside Reverse- Transcriptase Inhibitor (NNRTI). The NRTIs are Zidovudine (AZT) or Stavudine (d4T) with Lamivudine (3TC); the NNRTI components are either Nevirapine (NVP) or Efavirenz (EFV). Existing data regarding the effectiveness of Vonavir compared to other first-line ART regimens in increasing CD4+ T cell counts are unsatisfactory. METHODS: Immunological outcomes of 134 individuals who were on initial stage of antiretroviral therapy with Vonavir or a combination of Zidovudine/Lamivudine and Efavirenz were analyzed. The immunological response was then assessed during 28 weeks. RESULTS: Both groups demonstrated a significant increase in their CD4+ T cell count which was greater in Zidovudine/Lamivudine and Efavirenz treated group. We observed a noticeable increase in CD4+ T cells rates in the first three months of therapy; however, our results indicated a greater increase of cell counts in individuals with baseline CD4 lower than 100 cells/mm3 treated with Vonavir in first 12 weeks of treatment compared to those with higher baseline CD4. CONCLUSION: A rapid CD4+ Tcell increase occurred shortly after beginning ART consisting either Vonavir or combination of Zidovudine, Lamivudine and Efavirenz. Late increases in CD4+ T cell counts were more pronounced in therapy using Zidovudine/ Lamivudine and Efavirenz.

Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016.

AIMS: The aim of this study was to evaluate drug resistance patterns among Iranian people living with HIV who have taken antiretroviral therapy for 9-15 months. METHODS: A cross-sectional study was conducted between December 2015 and May 2016. Two hundred fifty-two blood samples were collected from all eligible HIV-infected patients at fourteen healthcare settings, located in major provinces in Iran. The samples were examined for presence of drug resistance strains and viral load level. Moreover, a phylogenetic tree, using neighbor joining, was constructed and HIV subtypes were determined. RESULTS: The most common subtypes were CRF35-AD (47.6%) and A1 (42.8%), followed by 45_CPX (4.8%) and C (4.8%). The resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors was reported as 19.2, 19.2, and 10.3%, respectively. M184I/V mutation was the most frequent (31.6%) mutation among NRTI-based regimens. Moreover, K103E/N was the most frequent (34.2%) NNRTI mutation. CONCLUSIONS: This is the first study to illuminate the emergence of the CPX genotype among Iranian patients. The drug resistance rate of NNRTIs was similar to that of NRTIs. By assessing drug resistance, it is possible to evaluate the efficacy of treatment and patient adherence to treatment.

Enhanced Immune Responses against HIV-1 with Adenovector (Gag and Tat) Prime/Protein Boost Regimen and GM-CSF Injection.

Vaccines against the HIV-1 virus offers the best hope for eliminating HIV-associated mortality. Recombinant adenovector type 5 (rAd5) vaccine is a potential candidate for preventive vaccine strategies. In this study, we evaluated the rAd5 prime/protein boost strategy in a murine model. We used rAd5 harboring single HIV-1 genes. These genes, including gag (p24) and exon1 of tat, were amplified from HIV-1 (clade A) RNA using nested PCR. Recombinant vectors were constructed, purified and then injected at 1012 viral particles into four groups, each comprising five mice. The groups were each assigned to receive one of rAd5 prime/protein boost Gag, Tat with and without recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), and rAd5 with and without genes. The humoral responses were evaluated using ELISA and cellular immune responses checked by cell proliferation and ELISpot assays (IL-2, IL-4 and IFN-γ). It was shown that compared with the rAd5 injection alone, the rAd5 prime/protein boost plan increased cellular immunity (p= 0.009) as well as humoral immunity (p= 0.009). Moreover, rGM-CSF as an adjuvant enhanced cell-mediated immunity and increased IL-4 expression (p=0.032). The results revealed that the simultaneous use of multiple antigens and heterologous prime/boost strategy can enhance both humoral and cellular immune systems. Moreover, subcutaneous injection of rGM-CSF increases IL-4 production and shifts the immune pattern to Th2. These strategies can potentially be used to develop an efficient HIV-1 vaccine.

Lack of Association between Interleukin-10 Gene Promoter Polymorphisms with HIV Susceptibility and Progression to AIDS.

BACKGROUND: Interleukin (IL)-10 is an important anti-inflammatory and immunomodulatory cytokine. Some authors believe that single nucleotide polymorphisms (SNP) in the promoter region of the IL-10 gene have been associated with susceptibility to HIV infection and progression to AIDS, but its role is not clearly defined yet. The present study was undertaken to evaluate the association between HIV infection susceptibility and progression with SNP in the promoter region of the IL-10 gene. METHODS: This study was carried out in 70 HIV infected patients (39 treatment naïve and 31 under treatment) and 31 matched healthy controls. The biallelic polymorphisms in the IL-10 gene promoter (-592 ,-1082) were analyzed by polymerase chain reaction and direct sequencing. RESULTS: At position -1082, G/A was the most common genotype and A was the most prevalent allele and at position -592, A/C was the most prevalent genotype and -592 C was the most common allele in HIV positive patients; although there was not any significant difference between cases and controls regarding genotypes and alleles of these regions. CONCLUSION: Our study showed that genetic polymorphisms of IL-10 promoter region may not associate with HIV infection outcome and the lack of this association suggests that other genes may influence on HIV infection course.

Fetal Sex Determination using Non-Invasive Method of Cell-free Fetal DNA in Maternal Plasma of Pregnant Women During 6(th)- 10(th) Weeks of Gestation.

In previous years, identification of fetal cells in maternal blood circulation has caused a new revolution in non-invasive method of prenatal diagnosis. Low number of fetal cells in maternal blood and long-term survival after pregnancy limited the use of fetal cells in diagnostic and clinical applications. With the discovery of cell-free fetal DNA (cffDNA) in plasma of pregnant women, access to genetic material of the fetus had become possible to determine early gender of a fetus in pregnancies at the risk of X-linked genetic conditions instead of applying invasive methods. Therefore in this study, the probability of detecting sequences on the Y chromosome in pregnant women has been evaluated to identify the gender of fetuses. Peripheral blood samples were obtained from 80 pregnant women at 6(th) to 10(th) weeks of gestation and then the fetal DNA was extracted from the plasma. Nested PCR was applied to detect the sequences of single copy SRY gene and multi copy DYS14 & DAZ genes on the Y chromosome of the male fetuses. At the end, all the obtained results were compared with the actual gender of the newborns. In 40 out of 42 born baby boys, the relevant gene sequences were identified and 95.2% sensitivity was obtained. Non-invasive early determination of fetal gender using cffDNA could be employed as a pre-test in the shortest possible time and with a high reliability to avoid applying invasive methods in cases where a fetus is at the risk of genetic diseases.