The introduction of the highly active antiretroviral therapy in the mid-1990s has significantly reduced morbidities and prolonged the lifespan of people living with HIV. However, the emergence of resistance to the antiretroviral drugs is becoming a major cause of treatment failure. While the problem of drug resistance is being tackled in developed countries, not much seem to be done in this regard in developing countries of Africa, Asia and Latin America. This review looked at the regional distribution of HIV groups and subtypes and how this has affected the pattern of antiretroviral resistance.
The review was sourced from papers presented at international conferences on HIV/AIDS and rational drug use, relevant journals and Medline search using the keywords--Antiretroviral drugs, drug resistance, HIV subtypes and resistance testing.
The types, groups, subtypes, sub-subtypes and recombinant forms of HIV-1 have been identified according to their geographical distributions. The evolution of HIV viral mutations, process (es) involved in development of primary and secondary antiretroviral drug resistance, including the role of HIV genetic polymorphisms, and transmitted resistance have been discussed.
The pitfalls in the current resistance testing based on HIV-1 subtype B have been highlighted. The design of resistance testing algorithm based on HIV-1 subtype non-B has been suggested for the developing world.
"Despite considerable success of highly activating antiretroviral therapy (HAART), AIDS has remained one of the most important health problems worldwide (11, 12). Emergence of resistant strains formation and toxicity of current available drugs make an impetus to find new anti-HIV therapy strategies (13, 14). Medical plants are promising candidates for developing new antiviral drugs. "
[Show abstract][Hide abstract] ABSTRACT: Avicennia marina (Avicenniaceae) is a species of mangrove tree used for treatment of small pox lesions in Persian folk medicine. The antiviral activity of methanol, ethanol, water, chloroform and n-hexane extracts was evaluated against HIV-1 and HSV. Methanol extract had the highest antiviral activity and the most polar fraction of this extract (fraction D) inhibited HSV with TI and SI values of 57.1 and 133; however, it showed mild activity against HIV with SI value of 6.25 (fraction 3). The anti-HSV activity of active fraction was confirmed using FLASH-PCR. Phytochemical investigation revealed that fraction D encompasses flavonoids compounds. The time-of-addition study demonstrated that fraction D disturbs viral replication after penetrating to the cell. A. marina was endowed with fragments by which found to be able to inhibit replication of HSV after entry but did not show significant potency against HIV-1. This promotes further investigation in anti-HSV drug discovery.
Iranian journal of pharmaceutical research (IJPR) 04/2013; 12(2):435-43. · 1.07 Impact Factor
"Despite the considerable success of anti-retroviral therapy (HAART), AIDS remains one of the most important world health problems. Emergence of resistance strains and toxicity of current available drugs make it impetus to find new anti-HIV therapy strategies. Setarud (IMOD™) is a natural medicine and includes herbaceous components manufactured by Parsroos Company in Iran (www.Parsroos.com). "
[Show abstract][Hide abstract] ABSTRACT: Setarud (IMOD™) is a herbal medicine with beneficial effect for patients suffering Human immunodeficiency virus (HIV) infection and has been approved for IV (intra venues) injection. The beneficial effect of IMOD administration for acquired immune deficiency syndrome (AIDS) patient has been proved in previous clinical trials. Here the in vitro inhibitory effect of IMOD against HIV-1, Herpes simplex virus (HSV) and murine leukemia viruses (MLV) was evaluated.
HIV single cycle replication and HSV plaque reduction assays were used to evaluate the anti-viral effect. The level of HIV replication was monitored by p24 capture Enzyme-linked immunosorbent assay (ELISA). The single round infection [with green fluorescent protein (GFP) reporter MLV and HIV], virucidal and time-of-additions (HSV) assays were utilized to determine the mode of anti-viral activity. The toxicity of IMOD for cells was monitored by XTT (sodium 3_-[1 (phenylaminocarbonyl)- 3,4-tetrazolium]-bis (4-methoxy-6-nitro)benzene sulfonic acid) cell proliferation assay kit.
IMOD inhibited 50% of HIV-1 and HSV replication (IC(50)) at 6.5 × 10(-4) and 4.3 × 10(-3)V/V concentrations, respectively. The IC(50) value against HIV-1 and MLV infection were 6 × 10(-4)V/V and 4.9 × 10(-4)V/V. Virucidal assay showed that IMOD reduces the potency of HIV and HSV particles to 41 and 54% of control, respectively. Time-of-addition study revealed that IMOD inhibits the replication of HSV at a stage after penetration of virions to the target cells.
Data from this study indicate that IMOD has significant anti-viral activity against HIV, HSV and MLV. Setarud could be subjected to further investigation after isolation of the constituents and determination of the toxic components.
Indian Journal of Pharmacology 07/2012; 44(4):448-53. DOI:10.4103/0253-7613.99301 · 0.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summarizes the available information on drug resistance in adults in resource-limited settings.
The online databases PubMed and Google Scholar, pertinent conference abstracts and references from relevant articles were searched for publications available before November 2011. Data collected after ART rollout were reviewed.
A total of 7 studies fulfilled the criteria for the analysis of acquired drug resistance and 22 fulfilled the criteria for the analysis of transmitted drug resistance (TDR). Acquired resistance was detected in 7.2% of patients on ART for 6-11 months, 11.1% at 12-23 months, 15.0% at 24-35 months, and 20.7% at ≥ 36 months. Multi-class drug resistance increased steadily with time on ART. The overall rate of TDR in all resource-limited countries studied was 6.6% (469/7,063). Patients in countries in which ART had been available for ≥ 5 years were 1.7 × more likely to have TDR than those living in a country where ART had been available for <5 years (P<0.001). The reported prevalence of TDR was 5.7% (233/4,069) in Africa, 7.6% (160/2,094) in Asia and 8.4% (76/900) in Brazil.
The emergence of drug resistance following access to ART in resource-limited settings resembles what was seen in resource-rich countries and highlights the need for virological monitoring for drug failure, drug resistance testing and alternative drug regimens that have proven beneficial in these resource-rich settings.
Jane Hitti, Elias K Halvas, Lu Zheng, Constantinos G Panousis, Joseph Kabanda, Frank Taulo, Nagalingeswaran Kumarasamy, Jean William Pape, Umesh Lalloo, Heather Sprenger, Karin L Klingman, Ellen S Chan, Deborah McMahon, John W Mellors
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