A wide variety of articles were reviewed that adopted a number of different study designs for their research. A number of different experiments were also looked at which demonstrated how resistances to certain HIV-1 anti-retrovirals are arising. As presented in the appendix, this specific section will evaluate the results from many randomized control trials (RCTs), case control studies, prospective cohort studies with and without controls, retrospective cohort studies with and without controls and cross-sectional studies.
HIV-1 integrase inhibitors:
HIV-1 integrase is one of the key enzymes required for the successful replication of HIV-1 and is often a common therapeutic target to help treat HIV-1 infections. Integrase is a …show more content…
“They looked at multiple coding sequences of the HIV-1 integrase enzyme form blood plasma samples of 61 patients. They categorized the main integrase region sequences as subtype B, with minor subtypes being C (CRF01-AE, CRF02-AG and CRF13-cpx), D and G. No major integrase drug resistance mutations have been observed in new patients beginning with integrase inhibitor treatment, however in 30 cases, polymorphic variations with the E157Q mutation were observed. This mutation was more common among subtype B (26 cases) than with non-B subtypes (5 cases). Major integrase inhibitor drug resistance mutations (G140S, Q148H, N155H, V151I, E92EQ, V151I, G163R) were notable in four of these cases. Time to the development of drug resistance ranged from 3 to 16 months with a mean increase of HIV viral load of 4.34 HIV-RNA copies/ml at the time of emergence of the major mutations.” (11) Figure 1 demonstrates four cases in which resistance to integrase inhibitors were observed.
In a study conducted by Piralla et al., HIV-1 integrase variability was analyzed using stored plasma samples from 95 patients infected with HIV-1, within a one year period from 2008 to 2009. Patients with no available plasma samples or viral load less than 1,000 HIV-RNA copies/ml plasma were excluded from the analysis. Their results demonstrate that primary mutations associated with resistance to integrase inhibitors were not detected in patients that have previously been treated with integrase
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As stated by Dr. N.A.S, finding a vaccine has been incredibly challenging due to the astonishing genetic diversity of the virus. While it is true that the genome of two HIV infected individuals can differ by up to 30%,6 it is not the integrase enzyme that causes this huge difference in the genomes as written by Dr. N.A.S. Reverse transcriptase is the error prone enzyme that makes multiple mistakes while copying RNA into DNA, which results in ~1 mutation in every new virus.6 The advantage of mutations for HIV is that these new changes are not
(2011) was a multi-continent, randomized, controlled trial to evaluate the effectiveness of antiretroviral therapy on the speed of the disease process among HIV-1 infected and HIV-1 uninfected partners. In the study, 1,763 HIV mixed status couples were grouped into either early antiretroviral and delayed therapy groups. Inclusion criteria consisted of the HIV-1 infected participant having a CD4 count between 350 and 550 with no previous antiretroviral therapy usage, except to prevent mother-baby transmission. Participants attended three monthly sessions and then quarterly sessions until ill or requiring an additional amount of antiretroviral drugs (Cohen et al, 2011). The uninfected partners were tested each quarter for seroconversion, the period in time in which antibodies become detectable. The research study concluded that early antiretroviral therapy initiation had a greater effect on CD4 count than delayed antiretroviral therapy. The average CD4 count in the early therapy group originated at 400 and increased to 603 after 12 months of ART. A decline of CD4 cells were noted in the delayed group (Cohen et al, 2011). The authors concluded that a higher incidence of HIV transmission was noted in African countries and adverse effects were more likely to occur in the early therapy group. Early therapy had a positive effect on the HIV-1 uninfected and HIV-1 infected
As have been described above, HIV can have a potential effect on immunological cells, which are important to protect the body from additional infections such as Tuberculosis (TB), Cytomegalovirus (CMV) and other viral or bacterial infections. An effective treatment is needed to reconstruct what HIV has damaged. Antiretroviral therapy (ART) is a common treatment to stop the viral replication and decrease the disease progression, which may lead to a vast decline of the morbidity and mortality. The standard treatment involves a combination of at least three drugs; often known as a highly active antiretroviral therapy (HAART) where the most common types are Nucleoside reverse transcriptase
Before we can explore the prevalence of HIV in the older adult population, we need to discuss the history of HIV and what it does. In the United States, HIV has been present since the mid 1970’s (CDC, 2016a). However, it is believed that the first human case of HIV occurred in the 1800’s (CDC, 2016a). During this time, hunters in Central Africa were killing chimpanzees and coming into contact with their blood (CDC, 2016a). Some chimpanzees in this region were infected with Simian Immunodeficiency Virus (SIV) (CDC, 2016a). When the humans were infected with SIV, it is thought to have mutated into what we know as HIV (CDC, 2016a).
Since the arrival of triple therapy, the challenge of sustained and complete viral suppression has been solved for the majority of patients . The major limiting factors for improving the long-term success of ART are tolerability and convenient pill burden . The latest class of the antiretroviral drug developed are Integrase inhibitors (INI). Dolutegravir (DTG) is an Integrase inhibitor, particularly focused on maintaining a favorable safety profile and a high efficiency rate, within a single-tablet regime (STR), it improves resistance barrier and allowing co-formulation with an NRTI backbone. Dolutegravir has been compared against both other classes of HIV anti-retrovirals as well as other integrase nuclear strand inhibitors. In August 2013, DTG was approved by FDA for its use in both patients who have never taken ART (ART-naïve) and patients who have taken ART (ART-experienced) . It is predicted that very soon a STR containing Dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) will become
Data from the Medical Monitoring project provided data for patients 18 years old and older, who were engaged in care, received ART prescription and managed to suppress their viral load (Bradley, et al., 2014, p. 1114). Specifically, patient HIV medical data was gathered from medical facilities that took place between January- April 2011 (Bradley, et al., 2014, p. 1114). The rate of ART prescription and viral load was documented within the participant’s medical chart preceding the survey. The authors statistical testing was conducted using the delta method (Bradley, et al., 2014, p. 1114) .
HIV has evolved in new varieties over the last dozen years. The virus is constantly changing due to natural selection and the environment of the patient's body. Inside the body, HIV replicates and every time it reproduces, random genetic copying mistakes mutations result in slightly different varieties of the virus going into the bloodstream. Some of these varieties will have traits that will make them resistant to certain drugs. Natural selection favors the drug resistant forms, causing them to survive and reproduce while causing medication to not work. It was discovered in 1970, that a patient suffering with HIV whose medication did not work, by going off the drugs made his virus population soon change from being resistant to every drug to then being susceptible. This was caused by the environment change in the body when stopping the medication. The non-resistant wild-type came back and started to replicate and soon outnumbered the drug-resistant strains. This resulted in a new treatment used today. If you take a patient that is resistant to medication, off the drugs for a certain amount of time and the virus reverts to the non-resistance wild-type, then hit it hard with a combination of drugs.
Description: HIV, also known as human immunodeficiency virus, attacks the immune system allowing the patient's body to not be able to protect itself. “HIV attacks and destroys the infection-fighting CD4 cells of the immune system. The loss of CD4 cells makes it difficult for the body to fight infections and certain cancers. Without treatment, HIV can gradually destroy the immune system and advance to AIDS” (National Health Institute). The disease was believed to originated in the Congo during the 1900’s, but now is present
HIV RNA (viral load) and CD4 T lymphocyte (CD4) cell count are the two surrogate markers of antiretroviral treatment (ART) responses and HIV disease progression that are used to manage and monitor HIV infection. The key goal of ART is to achieve and maintain durable viral suppression. If a patient has virologic failure, it means that they are unable to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL. Therefore, they should be assessed for virologic failure which include an assessment of adherence, drug-drug or drug-food interactions, drug tolerability, HIV RNA and CD4 T lymphocyte (CD4) cell count trends over time, treatment history, and prior and current drug-resistance testing results. Moreso, drug-resistance testing should be performed while the patient is taking the failing antiretroviral (ARV) regimen or within 4 weeks of treatment discontinuation.
Introduction: Human Immunodeficiency Virus (HIV) has become a global issue that has infected an estimated 35 million people living today1. The strain HIV-1 has been of experimental concern for years in hopes of a cure. This retrovirus directly infects the immune system by binding helper T-cells via the CD4 receptor. This allows for integration of the viral RNA into the T-cells, and causes the immune system to weaken by killing these immune cells. Advancements in research led to the use of highly active anti-retroviral therapy (HAART) for treatment, however this does not cure the patient of HIV but it suppresses the viral replication of HIV-1 to very low levels2.
Our chosen article is titled “HIV and AIDS News and Updates: New Strain of HIV Found in Cuba Which Can Develop Into a Full-Blown AIDS in a Span of Only 3 Years” written by Steff Lyn Smetham. It was published on November 5th, 2015 on the Crossmap online website. The article was written to inform the readers on a newly discovered strain of HIV, which develops faster than the average known types of HIV. This article mentioned many recently studied concepts including, the rate of disease progression, CRF19’s involvement in the AID’s rapid progression (AID’s-RP), the adverse effects of RANTES defense molecules, and proper HIV treatment. The general consensus is that the average rate of disease progression takes approximately 5 to 10 years to progress into AIDS, however, it is quite complicated to pinpoint the rate due to many factors. Based on many clinical studies done with a diverse group of patients in Cuba, CRF19 has shown to be one of the main recombinant subtype responsible for AIDs-RP. In addition, CCL5 and CCL2 of the RANTES family, have proven to be two specific chemokines that display the adverse effects . Finally, regardless of CD4+ count, treatment should be started immediately preferably with the common therapies Isoniazid preventive therapy (IPT) and Co-trimoxazole preventive therapy (CPT). The authors have used information through studies being done at the University of Leuven located in Belgium, and Professor Anne-Mieke Vandamme and a team
Drug resistance has become an obstacle in maximizing the clinical benefit of ART and consequently, routine HIV genotyping is recommended prior to ART initiation during viral rebounds and on the failure of an ART regimen. Successful PCR amplification of PR and RT genes is essential regardless of which method is used for sequencing. Results from this study show that not only it is possible to detect but also to characterize virus that continues to be produced in low levels in such patients. The samples with LLV were amplified to determine whether LLV present in patients on effective ART regimen resulted from the development of drug resistance. Out of the 31 samples that were amplified using the optimized protocol, seven had no product by the time library preparation was set up. The likelihood of the loss of PCR products during clean up exists. There is a high possibility of mishandling the sample during shipping and receiving of the samples. Instead of screw-cap tubes, the samples were shipped on a 96 well plate with a film on top, which is not ideal as per protocol. Additionally, the ice packs had melted by the time the lab received samples for sequencing. Since DNA does not evaporate easily, lack of proper shipping and storage techniques could have led to samples spilling or possible degradation.
Phenotypes are more expensive than genotypes but have more limited availability and also a problem of interpretation exists, the values (or “cutoffs”) that define resistance phenotypically have been based on the technical variability of the assay or, more recently, the biologic variability of wild type strains. Two companies have developed standardized assays amenable to high-throughput performance (Virco, Mechelen, Belgium and ViroLogic, South San Francisco, CA, USA) (Hertogs et al., 1998; Petropoulos et al., 2000). Both assays amplify the entire PR, much of RT and some of gag from HIV-1 RNA extracted from patient plasma.
HIV becomes drug resistance when the ARV treatments’ are not adhered to. Once the patient has taken their antiretroviral (ARVs) medication then stops the HIV is able to replicate and will do so at a rapid rate. As a result mutations are very common (Jen Gorgan and Ruth Suter;2009)
Introduction. Human immunodeficiency virus type 1 (HIV-1) has infected over 33.2 million people world-wide to date . There is a plethora of new and upcoming drugs that are being used to combat against human immunodeficiency virus. Although effective, the drugs that are being used to combat against HIV-1 have also been known to cause resistance, adverse effects and toxicity to the mitochondria . HIV-1 is a retrovirus that belongs to a subfamily of retroviruses called lentiviruses . HIV-1 causes a slow depletion of the immune system and is considered a slow degenerative disease. New drugs that combat against HIV-1 entering into different cells has raised interest due to the fact that these new drugs are able to work against drug resistant viruses that can infect the cell.