Monitoring and Evaluation of HIV

Probationary rubric:Monitoring and Evaluation of HIV Drug Resistance in Patients on Antiretroviral Therapy

Introduction

The intent of this protocol is to measure the outgrowth of HIV drug opposition by supervising virologic response and forms of HIV drug opposition in patients on combination antiretroviral therapy ( ART ) in University of Malaya Medical Centre ( UMMC ) where there is rapid scaling up of antiretroviral therapy for people with HIV/AIDS. Secondary countries for rating include finding the frequence of virologic suppression ( HIV RNA & A ; lt ; 400 copies/ml ) among patients taking first-line ART regimens at 12, 24, 36, and 48 months after ART induction or after exchanging to second-line regimens, measuring single patient forecasters of virologic suppression including old history of exposure to antiretroviral drugs and attachment, measuring programmatic forecasters of virologic suppression including prescribing patterns, support for attachment, and continuity of drug supply.

Further analyses may include the rating of forms of noticeable HIV drug opposition mutants in cohorts of patients get downing first-line ART in UMMC at baseline and 12, 24, 36, and 48 months, and before halting ART or exchanging to a second-line regimen, by sequencing the relevant parts of the HIVpolcistron in all specimens in which the HIV viral burden is = 400 copies/mL. The plan will try to document the extent of informal and non-optimal ART received by patients before get downing first-line ART and the extent to which it predicts forms of drug opposition mutants.

Prevalence of opposition will be calculated and classified as & A ; lt ; 5 % , 5-15 % , and & A ; gt ; 15 % ( Bennett, 2008 ) . Prevalence of HIVDR will be calculated for specific antiretroviral ( ARV ) drug categories and persons ARV drugs within UMMC. Changes in prevalence of HIVDR within each site over the survey continuance will be assessed utilizing chi-square trials. HIV-1 subtype distribution can besides be evaluated utilizing the nucleotide sequence information obtained.

Statement of Problem

Antiretroviral intervention ( ART ) for HIV is being scaled up quickly in Malaysia. The scale-up of antiretroviral drug entree in the state necessitates the development of an effectual surveillance plan for familial HIV drug opposition ( HIVDR ) to guarantee that the limited drugs available are used to the best consequence across the population.

The WHO is cognizant of the importance of puting up effectual plan and has developed a set of public heath rules to minimise HIVDR. These includes supplying appropriate ART entree, ordering and use of ART, furthering ART attachment, back uping bar of HIV transmittal plans and taking appropriate action based on monitoring and surveillance ( Bennett, 2008 ) .

HIV-1 antiretroviral drug opposition consequences from one or more mutants in a strain of HIV-1, that enhances the reproduction of the virus in the presence of an antiretroviral drug compared to wild-type virus. To observe this mutant two methods had been set up one is genotypic and the other is phenotypic trial. The usage of these trial have been shown to better endurance and immune response when used to steer clinical determinations made for patients who have failed one or more drug regimens.

Aim

The intent of this protocol is to measure the extent of familial HIV drug opposition in intervention naive HIV positive persons in Malaysia.

Secondary aims of this protocol include placing the categories of drugs to which HIV is immune, and detect alterations in HIV prevalence over clip.

Research Questions

What is the drug opposition in naive patients?

When does the first drug opposition occur?

Which intervention triggers a higher drug opposition form in UMMC?

Literature Review

1. Global Expansion of Antiretroviral Therapy

In 2001, the United Nations General Assembly Special Session on HIV/AIDS recommended that antiretroviral ( ARV ) drugs should be made available in resource-limited states to turn to the disparity between rich and hapless states sing entree to antiretroviral intervention ( ART ) . Following this recommendation, the World Health Organization ( WHO ) elaborated public wellness guidelines to back up and ease the execution of ART in resource-limited scenes. Key constituent of the guidelines include 1 ) Standardization and simplification of ARV regimens ; and 2 ) Use of science-based grounds to back up intervention protocols and to avoid usage of substandard intervention taking to hapless result and the outgrowth of HIV drug opposition strains ( Organization, 2003 ) .

2. 2. HIV Drug opposition proving
1. Genotypic HIV drug opposition proving

Genotypic proving evaluates the nucleotide sequences from which the virus ‘s contrary RNA polymerase ( RT ) and protease enzymes ‘ amino acid sequences can be deduced. The nucleotide sequences of these two parts of thepolcistron in the HIV genome are compared to those of a specified wild-type mention virus. Any alteration from wild-type is reported as a alteration in the amino acid at a specific codon of the enzyme.

2. Phenotypic HIV drug opposition proving

In vitrophenotypic proving uses the HIV-1 RT and protease parts of thepolcistron derived from the HIV infecting an person, and uses recombinant DNA techniques to bring forth a virus with these parts incorporated. Assorted methods are employed to compare the ensuing virus ‘s susceptibleness to ARV drugs. In vitro, HIVDR is defined as the ability of a virus to turn in the presence of an ARV drug that usually inhibits growing, as compared with the growing of a susceptible control ( wild-type ) virus. Susceptibility in vitro is often expressed as the concentration necessary to suppress the growing of a virus by 50 % ( IC50 ) .

Virtue phenotypic HIV drug opposition proving

Virco®TYPE HIV-1 is a refined HIV-1 drug opposition analysis trial that provides a combination of genotypic and phenotypic information. The trial consequences are interpreted in a clinical context with clinical cut-off values to supply public-service corporation for doing curative determinations. Virco®TYPE HIV-1 utilizations bio-informatics engineering, Virtual Phenotype™- LM to cipher phenotypic opposition from the genotype. The phenotype anticipations are based on a big and continuously turning database of antecedently determined genotypes and phenotypes ( hypertext transfer protocol: //www.vircolab.com/product-center/vircotype-hiv-1 ) .

1. Sample usage for HIV drug opposition proving
1. Plasma
2. Serum
3. Dried Blood Spots
3. Surveillance and monitoring of HIV drug opposition
1. Industrialization states
2. Developing states
4. Justification for HIV drug opposition monitoring in individuals on intervention

Mention

Bennett, D. E. , Bertagnolio, S. , Sutherland, D. , Gilks, C.F. ( 2008 ) . The universe wellness organisation ‘s planetary scheme for bar and appraisal of HIV drug opposition.Antiviral Therapy, 13( 2 ) , 1-13.

Organization, W. H. ( 2003 ) .Scaling up antiretroviral therapy in resource-limited scenes: intervention guidelines for a public wellness attack.Retrieved 22 / 9 / 2009, from hypertext transfer protocol: //www.who.int/hiv/pub/prev_care/en/arvrevision2003en.pdf