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| HAART Therapy Suppresses Mother to Child Transmission Through Breast Milk |
Documented mother-to-child transmission of HIV-1 virus through breastfeeding prompted public health officials around the world to reccomend formula feeding for HIV positive mothers. Unfortunately, while avoiding the possible risk of viral transmission, the newborns were missing out on the essential health benefits of breast milk. Recently Highly Active Antiretroviral Therapy (HAART) was documented to reduce the viral load in breastmilk. In a recent study, HAART initiated during or right after pregnancy reduced the amount of cell-free HIV-1 RNA in breastmilk which suggests it could potentially lower rates of mother -to--child transmission through breastfeeding. Haart therapy did not however reduce loads of HIV-1 DNA. The implications of this second finding requires further investigation. Shapiro, Roger L. et al. "Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in Breast Milk." The Journal of Infectious Diseases. 2005; 192: 713-9.
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| HIV-1 subtype C viruses almost exclusively use the Chemokine receptor CCR5 as coreceptor for cell entry |
HIV-1 subtype C viruses almost exclusively use the chemokine receptor CCR5 as a co-receptor for entry into the cell. Gp120, an envelope protein of HIV, binds to both CD4 and a coreceptor, which is usually CCR5. Use of a second co-receptor, CXCR4, has been found in HIV-1 subtypes A, D and B. During early infection the dominant co-receptor is CCR5, but studies have shown that this may switch during the course of infection from CCR5 to CXCR4. Evidence shows that this switch is correlated with a higher rate of disease progression. Researchers in California and Zimbabwe have discovered that treatment of patients infected with subtype C virus with antiretrovirals may infact increase this switch to CXCR4 tropism which is then linked to rapid disease progression. Johnston et al. High Frequency of Syncytium-Inducing and CXCR4-Tropic Viruses among Human Immunodeficiency Virus Type 1 Subtype C-Infected Patients Receiving Antiretroviral Treatment. Journal of Virology. 2003; 77: 7682-8. |
| Nevirapine reduces Intrapartum HIV-1 transmission |
Mother-to-Child-Transmission is a constant danger for children born to HIV-infected mothers especially in developing nations. Treatment of mothers during labor with drugs such as Nevirapine has been shown to significantly reduce this risk. Researchers have discovered that while single-dose Nevirapine does reduce intrapartum HIV-1 transmission, it may also select for nonnucleoside reverse-transcriptase inhibitor resistance in breast milk and plasma. As most HIV-1 positive women in resource-constrained countries breast feed their children, and up to one third of MTCT is due to breast feeding, Nevirapine treatment protects infants from infection during birth, but may put them at greater risk for contracting drug-resistant virus from breast milk.
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| TAR genomic region studied as possible target for antiretroviral therapy |
Much research and development goes into figuring out treatment and vaccine options for the HIV-1 virus as the AIDS pandemic spreads globally. Many approaches aim to stop retroviral replication, many investing in the antisense strategy focusing on polyamide nucleic acids.The transactivator responsive region (TAR) of the HIV-1 genome has recently been discovered as a possible target of antiretroviral medication. FACScan analysis of the efficiency of cellular uptake of conjugated MTD peptides, penetratin, tat peptide, transportan-27, and two truncated derivatives of transportan-21 and transportan-22, to a 16mer PNA targeted to the TAR region showed that uptake was concentration dependent. Interestingly it also revealed PNA TAR penetratin congugate was most efficient with MTD. This leads researchers to believe that anti-HIV-1 PNA in conjugate with MTD peptides inhibit HIV-1 in vitro replication and could also reduce HIV-1 infectivity. Tripathi S. et al. Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides. 2005 Aug 2;33(13):4345-56. Print 2005. Retrovirus-mediated anticancer therapy proves effective Retroviruses have been studied for their possible anti-cancer properties. Inhibition of tumor angiogenesis relies on the inhibition of the neovasculature. In this study, a vascular endothlial growth factor receptor-2 (sFLK-2) was mediated by retrovirus and seen to inhibit tumorgenicity in genes S180, MCF-7, and B16 live cells. This is a big step in using retrovirus mediated therapy as anti cancer therapy and plays a big role in anti cancer treatment development.
Kou B. et al. Gene therapeutic exploration: retrovirus-mediated soluble vascular endothelial growth factor receptor-2 (sFLK-1) inhibits the tumorigenicity of S180, MCF-7, and B16 cells in vivo. Oncol Res. 2005;15(5):239-47. HIV-1 Infection and the Central Nervous System A high viral load of HIV-1 virus in the cerebrospinal fluid can lead to neurological symptoms in infected patients. While the Central Nervous System is not typically a "sanctuary site" 39% of HIV-1 infected patients displayed neurological symptoms. In this recent study, researchers demonstrated that antiretroviral therapy directly injected into the cerebralspinal fluid can have a therepeutic effect on patients experiencing symptoms. Mellgren A. et al. Cerebrospinal fluid HIV-1 infection usually responds well to antiretroviral treatment. Antivir Ther. 2005;10(6):701-7.
CXCR4-using viruses like HIV-1 Explained HIV-1 initially uses CCR5 receptors to gain entry into the cell; however natural evolution results in a switch to CXCR4 usage, which is associated with expanded target cell range and worsened cell prognosis. Why this switch takes so long is puzzling because it only takes one to two mutations to occur. Scientists investigated potential obstacles to CCR5-CXCR4 switching. It was determined that a diminished replication fitness, less-efficient co-receptor use, and unique mutational pathways have been suggested as reasons why CXCR4-using viruses take so long to emerge.
Pastore et al. Intrinsic Obstacles to Human Immunodeficiency Virus Type 1 Coreceptor Switching. Journal of Virology. 2004; 78:7565-74. |