HIV Drug Resistance – In 2010, people worldwide living with HIV and AIDS were estimated to be 34.0 million. Recently, the latest report by the United Nations program on Acquired Immuno-Deficiency Syndrome (AIDS) revealed that about 36.7 million (30 million – 42.9 million) people globally are living with Human Immuno-Deficiency Virus (HIV).
Out of this number, 20.9 million people have been put on antiretroviral therapy and 1.8 million (1.6 million – 2.1 million) new cases are reported every year. Although the sub-Saharan Africa region has the highest prevalence of HIV and AIDS, the current introduction and distribution of antiretroviral drugs and therapy have in a way resulted in the decline of the epidemic in this region.
Ghana as a developing country has been able to control this epidemic to some extent, even though more work has to be done. The prevalence of HIV in Ghana declined from a peak of 3.6% in 2003 to 2.1% in 2011 due to a program implementing a strategy for achieving universal access to the Anti-Retroviral Therapy introduced by the National AIDS Commission. Since the commission of the National AIDS Control Program, the number of persons receiving ART has increased drastically from 3663 persons in 2005 to 79131 in 2014.
The prevalence of the Human Immunodeficiency Virus disease has declined remarkably through the introduction of ART. The use of combinations of ART has proven to be effective in controlling the progression of this deadly disease. It has also helped to prolong the life-span of infected persons around the world. This has raised the hope to most Persons Living with HIV (PLHIV), but the benefits of this therapy could be compromised in the likely event that the virus could develop some resistance to the drug.
HIV Drug Resistance
The ART agent that is used to treat HIV infection has been grouped into four distinct classes. They are the nucleoside and nucleotide analogues which acts as deoxyribonucleic acid (DNA) chain terminators and inhibit Reverse Transcription of the viral RNA genome into DNA, non-nucleotide reverse- transcriptase inhibitors in which its main function is to bind and inhibit reverse transcriptase (enzyme that does the reverse transcription), protease inhibitors, which target the viral protease, the enzyme required for the cleavage of precursor proteins (gag and gag-pol) permitting the final assembly of the inner core of viral particles and entry inhibitors which main function is to prevent the penetration of the virus into the target cells.
Combinations of various ART are now used in the treatment of HIV. They are also called highly active antiretroviral therapy (HAART). Currently, HAART regimens comprise of two nucleoside analogues and, either protease inhibitor or non- nucleoside reverse transcriptase inhibitor. The first-line regimen of ART recommended in Ghana is the combination of two nucleoside reverse-transcriptase inhibitors (NRTIs) and a non-nucleoside reverse-transcriptase inhibitor (NNRTI). Specifically, the two NRTIs selected are lamivudine (3TC) and either zidovudine (AZT) or stavudine (d4T), then either nevirapine (NVP) or efavirenz (EFV) as the NNRTI.
For the second-line regimen in Ghana, two protease inhibitors (PIs) are available, nelfinavir (NFV) or lopinavir/ritonavir (LPV/r), either of which is recommended to use with two NRTIs, abacavir (ABC) and either tenofovir (TDF) or didanosine (ddI).
It should be noted that drug-resistant variants selected during ART have the potential to be transmitted to others. Recent researches have shown that drug-resistant HIV has been widely described in ART-naïve individuals. The overall prevalence of resistant HIV – 1 conducted in various parts of the world has its transmission reaching 12.9% in North America, 10.9% in Europe, 6.3% in Latin America, 4.7% in Africa and 4.2% in Asia.
This report shows that the higher prevalence of drug-resistant HIV- 1 transmission is high in areas where there is massive coverage of ART that is in most developed countries. With the massive distribution of ART, the transmission of resistant-HIV 1 has increased from 2.8% before 2001 to 5.3% after 2003 in African countries. Selective pressure from various antiretrovirals (ARV’s) could lead to the virus developing a kind of resistance to ART, as a result, reduces the effectiveness of ARV’s leading to expedited treatment failure, limiting the available drug options.
HIV Drug Resistance
Early in HIV infection, the founding virus inoculum saturates the majority of target cells and transmitted drug-resistant viruses become well established in long-term reservoirs that allow drug resistance to persist. Because many resistance mutations reduce replicative fitness, drug-resistant viruses not under ART drug pressure can reverse resistance mutations to become more fit.
Over time, revertants outcompete the drug-resistant viruses to become the predominant viruses in circulation; however, the rates of mutant virus decay can vary substantially because of differences in fitness cost. Moreover, the cost imparted by a drug resistance mutation to viral fitness can be modulated by other resistance mutations in the virus, and thereby accelerate or retard decay of the mutation.
HIV-1 drug resistance mutations are conventionally detected by bulk sequence analysis of the virus sample. Bulk genotyping may detect certain mutations in clinical samples at frequencies as low as 10%; however, the detection limitation does not allow for reliable identification of variants that constitute less than 20%–30% of the virus population in a sample.
This detection limit is a concern because most newly diagnosed persons have been infected for several months to years, providing time for drug-resistant viruses to decay to levels that conventional testing is not able to detect. Clinicians use or depend on CD4 counts plus clinical symptoms to monitor and treat this deadly disease though the golden standard for the monitoring of HIV is checking the infected person’s plasma viral load.
Plasma viral load resources are limited in most developing countries though a few centers operate it only a few persons could afford. A significant proportion of PLHIV may suffer virologic failure while continuing to take first-line ART. This may encourage the development and accumulations of drug-resistant mutations and affect future treatment efforts.
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