Mechanism of ART Therapy in HIV Patients
Sabir M, Ahmed L, Asif U and Amjad A
Published on: 2024-07-13
Abstract
Antiretroviral therapy is transforming HIV from a fatal disease to a manageable condition.
Abstract: Infection with the Human Immunodeficiency Virus (HIV) was formerly thought to be fatal. However, the development of antiretroviral medication (ART) has transformed HIV treatment. This research investigates the impact of ART on HIV patients, focusing on its mechanisms of action, efficacy in viral suppression and immune system reconstitution, and function in HIV transmission prevention. We describe how ART regimens have evolved from early monotherapies to today's extremely successful combination treatments (extremely Active Antiretroviral Therapy, HAART). We also discuss ART-related issues, including as adherence, medication resistance, and probable adverse effects. Finally, this study demonstrates how ART has changed HIV management, enabling persons with HIV to live long and healthy lives.
Keywords
HIV; Antiretroviral therapy; TreatmentIntroduction
Human immunodeficiency virus (HIV) infection weakens the immune system, making people susceptible to opportunistic infections and cancer. Prior to the development of antiretroviral therapy (ART), HIV infection moved inexorably to AIDS (acquired immunodeficiency syndrome), a terrible disorder with a high death rate. The development of ART transformed HIV management. This extremely efficient treatment method employs a mix of drugs from diverse pharmacological classes to attack HIV at distinct phases of its reproduction. By inhibiting viral replication, ART significantly reduces viral load in the bloodstream, allowing the immune system to recuperate and fend off infections. This study investigates the influence of ART on HIV patients. We will look at how ART works, how effective it is at suppressing viral load and improving immune function.
Live Cycle Of HIV
The course of the HIV life cycle is complicated, but it is well known. Scientists have developed drugs to target certain stages of the HIV replication cycle and stop the virus from growing by knowing how the virus replicates itself. A summary of the seven phases of the HIV life cycle is provided below:
- Binding
- Fusion
- Reverse Transcription
- Integration
- Replication
- Assembly
- Budding
Binding: HIV's envelope proteins attach to specific receptors on CD4 cells, which are immune system cells.
Fusion: Following binding, the HIV envelope fused with the membrane of the CD4 cell, allowing the viral core to enter the cell.
Reverse Transcription: HIV releases its RNA genetic material inside the cell, which is then converted into double-stranded DNA by an enzyme known as reverse transcriptase.
Integration: The viral DNA is then carried to the nucleus of the CD4 cell. Integrase is another enzyme that inserts viral DNA into the CD4 cell's DNA. At this phase, HIV becomes a provirus.
Replication
Proviruses do not multiply on their own. Instead, it waits for the CD4 cell to activate. When a CD4 cell is activated, viral DNA is duplicated alongside the host cell's DNA. This new viral DNA can be used to make new HIV particles.
Assembly
The copied viral DNA provides the instructions for the production of new viral proteins and RNA. The new viral components are then put together.
Budding
The formed HIV particles emerge from the CD4 cell membrane, carrying a portion of the cell membrane with them. These new HIV particles can subsequently infect more CD4 cells, so continuing the replication cycle.
Understanding the HIV life cycle is critical for designing successful HIV treatment strategies. Antiretroviral therapy (ART) is a group of drugs that target distinct stages of the HIV life cycle. By inhibiting one or more steps of the cycle, ART can halt HIV replication and aid to sustain the immune system.
Progression of HIV
HIV infection progress through 3 stages
- Acute HIV Infection
- Chronic HIV Infection
- AIDS (Acquired Immunodeficiency Syndrome)
Acute HIV Infection
This is the first stage, which normally lasts 2-4 weeks after getting the virus. Some people get flu-like symptoms during this time, while others do not. At this point, the amount of HIV in the blood (viral load) is extremely high.
Chronic HIV Infection
Left untreated, this stage can linger for years, if not decades. During this time, HIV multiplies at a slower rate. The infected person may not have any obvious symptoms, or they may be minimal. However, the virus is steadily weakening the immune system by attacking CD4 cells, which are white blood cells that aid in the fight against infection.
AIDS (Acquired Immunodeficiency Syndrome)
This is the most advanced stage of the HIV infection. It happens when the immune system is significantly weakened, leaving the person vulnerable to opportunistic infections. A person with AIDS is diagnosed based on their CD4 cell count or the presence of specific diseases.
What is ART?
The term ART refers to antiretroviral therapy. It's a combination of drugs that greatly reduces the course of HIV.
History of ART
The history of ART (Antiretroviral Therapy) for HIV is a fascinating tale of scientific development and the fight against a lethal disease. Here's a glance at some major milestones:
Early Days (1930s-1980s)
Pre-ART Era: There were no viable medicines available during the early stages of the HIV epidemic (which was identified in the 1980s). HIV infection developed to AIDS, resulting in a large number of deaths.
Search for Treatments: Researchers were anxiously looking for strategies to combat HIV.They investigated several techniques, including as early antiviral medicines and immune-boosting therapy. However, these efforts generated only little success.
The Turning Point: The Development of Combination Therapy (1980s-1990s)
A New Hope
The late 1980s saw a breakthrough with the discovery of AZT (zidovudine), the first FDA-approved HIV medicine. However, AZT's potency declined as the virus developed resistance.
Combination Therapy
The concept of combination therapy, which employs numerous medications to target HIV at various stages of its reproduction cycle, emerged as a crucial method. This method resulted in dramatically improved treatment outcomes.
Protease Inhibitors
The introduction of protease inhibitors in the mid-1990s signified a significant advancement. These medications efficiently prevented HIV's ability to create new virus particles, resulting in a substantial drop in viral load and a considerable improvement in patient health.
The Modern Era of ART (1990s-Present)
Highly Active Antiretroviral Therapy (HAART)
The development of highly active antiretroviral therapy (HAART) in the late 1990s transformed HIV treatment. HAART regimens often include numerous medication classes, which maximize viral suppression while considerably lowering the risk of opportunistic infections.
Reduced Side Effects and Improved Quality of Life
Newer generations of ART drugs have less side effects and more flexible dose schedules, which leads to a higher quality of life for patients.
Ongoing Research
ART research continues today. Scientists are looking into more potent drugs with fewer adverse effects, long-acting injectables for better adherence, and potential HIV cures.
The Legacy of ART
The introduction of ART has reduced HIV from a life-threatening sickness to a tolerable chronic condition. It has substantially improved the lives of millions of HIV patients worldwide. The narrative of ART exemplifies scientific advancement, patience, and the continual search for a remedy.
Antiretroviral therapy, or ART, is a combination of drugs that greatly reduces the course of HIV infection. Here's an overview of what ART does:
Targets HIV Replication
HIV targets CD4 cells, thereby weakening the immune system. ART drugs target several stages of HIV replication, limiting its ability to replicate and spread.
Protects Immune System
By inhibiting the virus, ART permits CD4 cells to recover and boost the immune system, making the body less susceptible to opportunistic infections.
Reduces HIV Transmission Risk
When HIV is undetectable in the blood after persistent ART medication, the risk of transferring the virus to sexual partners is extremely low. This is referred to as U=U (Undetectable = Untransmutable).
Overall, ART is a strong treatment that changes HIV from a life-threatening sickness to a manageable chronic condition.
Considerations of HIV
When contemplating ART (Antiretroviral Therapy) for HIV patients, there are several important considerations to consider. Here's a summary of some major factors:
Efficacy
Adherence is Key: ART works best when taken on a consistent basis and exactly as advised. Skipping doses or failing to complete the whole regimen can cause the virus to develop resistance to the drugs.
Long-Term Treatment: ART is often a life-long treatment. While current research investigates potential solutions, continuous drug use is critical for HIV management.
Side Effects
Medications Can Have Side Effects
Symptoms may include nausea, tiredness, headaches, or dizziness. These are often mild to moderate and often improve with time. In addition, newer drugs with less adverse effects are now accessible.
Drug Resistance
If medications are not taken properly, HIV might evolve and develop resistant to them. This can make it more difficult to control the infection over time. Testing for viral load on a regular basis helps to monitor for resistance.
Additional Considerations
Drug Interactions
Some drugs may interact with ART, so it is critical to inform the doctor about all prescriptions (including herbal supplements).
Lifestyle Factors:
Maintaining a healthy lifestyle that includes a balanced diet, frequent exercise, and appropriate sleep might help ART work more effectively and enhance overall health.
Mental Health
Having a chronic disease can be difficult. In addition to antiretroviral therapy, mental health assistance can be a crucial element of controlling HIV.
Overall, antiretroviral therapy (ART) is a potent tool for HIV management, but it requires commitment and ongoing communication with a healthcare professional.
Classes of ART Medications
The term ART refers to antiretroviral therapy. It is a combination of drugs used to inhibit the Human Immunodeficiency Virus (HIV). HIV affects the immune system by destroying CD4 cells, which are essential for combating infections. ART works by interfering with HIV replication at several stages, preventing the virus from replicating and infecting new cells. There are several different kinds of ART drugs, each with a unique mechanism of action:
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Integrase Strand Transfer Inhibitors (INSTIs)
- Protease Inhibitors (PIs)
Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
These medications mimic the building blocks used by HIV to create genetic material (RNA). Once integrated into the developing viral DNA chain, NRTIs trigger chain termination, preventing the virus from reproducing.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
NNRTIs, unlike NRTIs, do not directly inhibit viral DNA synthesis. Instead, they bind to a specific location on the reverse transcriptase enzyme, preventing it from transcribing HIV RNA to DNA. This essentially stops HIV replication in its tracks.
Integrase Strand Transfer Inhibitors (INSTIs)
These drugs target the integrase enzyme, which is required for HIV to integrate viral DNA into host cell DNA. INSTIs prevent HIV from infiltrating the cell and propagating the virus by inhibiting integrase.
Protease Inhibitors (PIs)
HIV requires protease to break down freshly generated proteins into smaller, more functional pieces. PIs limit the activity of protease, leaving viral proteins inert and preventing the generation of mature, infectious HIV particles.
Clinicians can achieve a synergistic effect by mixing ART medications from different classes, resulting in a considerable reduction in viral load in HIV-positive individuals. This helps to maintain immune system function and prevents the development of AIDS (Acquired Immunodeficiency Syndrome), the most advanced stage of HIV infection.
Mechanism of ART in HIV Patients
HIV, the Human Immunodeficiency Virus, weakens the immune system by attacking CD4 cells, crucial components for fighting off infections. Antiretroviral Therapy (ART) isn't a cure, but a powerful tool to manage HIV by targeting different stages in its lifecycle, preventing replication and keeping the virus under control. Here's how ART works:
Taking aim at different stages
ART is a multi-drug approach, mixing drugs from different classes, each with a distinct target in the HIV lifecycle.
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Consider HIV utilizing its RNA as a template to construct DNA copies of itself within your cells. NRTIs function like Trojan horses. They mimic the building components (nucleosides) required by HIV for its DNA, but lack crucial activity. When they are incorporated into the viral DNA chain, they trigger a "chain termination," which stops the process and prevents new HIV copies from being made.
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
NNRTIs specifically target the reverse transcriptase enzyme. They bind to a specific area, changing the enzyme's structure and rendering it inactive. This effectively disrupts the HIV DNA replication machinery.
Protease Inhibitors (PIs)
To transmit the infection, HIV must first replicate its genetic material and then construct new viral particles. PIs target protease, a crucial enzyme that breaks down viral proteins into functional versions. PIs prevent mature, infectious HIV particles from forming by inhibiting protease activity.
Entry Inhibitors (EI)
These individuals are the gatekeepers. EIs work in the early stages of infection, preventing HIV from adhering to and fusing with CD4 cells' outer membrane. This effectively prevents the virus from entering the cell altogether.
Combination is Key
Because HIV can mutate, taking a single treatment can result in the development of resistance. As a result, ART regimens frequently include drugs from multiple classes. This multifaceted approach makes it substantially more difficult for HIV to acquire resistance and ensures long-term viral suppression.
ART significantly reduces the viral load in the body by efficiently targeting multiple stages of the HIV lifecycle, allowing the immune system to recover and combat infections. However, ART is not a cure and requires lifelong devotion. It is also crucial to know that ART might cause adverse effects, which are usually tolerable.
Combination Therapy: The Core of ART in HIV Patients
HIV, or Human Immunodeficiency Virus, weakens the immune system by attacking CD4 cells. Antiretroviral therapy (ART) is not a cure, but rather a strong tool for managing HIV by tackling different stages of its lifecycle. However, the main power of ART is combination therapy, which employs a smart mixture of medicines to achieve optimal success.
Why Combination Therapy
Monotherapy, or the use of only one medicine, is a prescription for disaster. HIV is a clever virus that is prone to mutations. Mutations can occur when a single medicine is exposed to an organism for an extended period of time, rendering it useless. This is referred to as drug resistance. Combination therapy addresses this issue with a multifaceted approach. Here is how it works:
Multiple Targets: Different kinds of ART medications target different stages of the HIV lifecycle. Combining medications from different classes ensures that even if one drug is mutated, the others are still effective, keeping the infection under control.
Synergy: Certain drug combinations can have a synergistic impact, which means that the combined action is higher than the sum of the separate effects. This results in a more robust suppression of HIV viral loads.
Durability: Combination therapy minimizes the likelihood of drug resistance emergence by addressing multiple stages and utilizing synergy. This results in more long-lasting HIV suppression.
How Combination Therapy Works in Practice
Clinicians carefully create a combination regimen taking into account a patient's health status, drug resistance history, and probable side effects. Here's an example breakdown:
Number of Drugs
Combination therapy often includes three or more medicines from different classes, such as NRTIs, NNRTIs, INSTIs, and PIs.
Considerations
When designing the regimen, factors such as side effects, drug interactions, and individual needs are taken into consideration.
Benefits of Combination Therapy
The efficacy of ART depends on combination therapy. Here are several significant advantages:
Suppressed Viral Load
Combination therapy reduces the amount of HIV virus in the bloodstream to undetectable levels by targeting different stages.
Improved Immune Function
With a reduced viral load, the immune system can recuperate, combat infections, and improve overall health.
Reduced Risk of Transmission
When viral load is undetectable, the risk of HIV transmission to others is extremely minimal. While combination therapy is an effective strategy, it's vital to realize that:
Lifelong Adherence
Strict adherence to the treatment regimen is critical for long-term viral suppression and avoiding drug resistance.
Side Effects
Although treatable, several ART medicines might cause adverse effects that necessitate monitoring and possibly adjusting the protocol.
Conclusion
Combination therapy is the cornerstone of HIV treatment. By deliberately mixing medications that target distinct stages of the HIV lifecycle, it successfully suppresses the virus, strengthens the immune system, and improves general health for those living with HIV.
Importance of ART for HIV
ART, or Antiretroviral Therapy, is an essential treatment for HIV patients. Here’s why it matters:
Suppresses the Virus
ART is a mix of medications that drastically reduce the amount of HIV in the bloodstream, known as the viral load. This reduced viral load makes it considerably more difficult for HIV to infect the immune system.
Boosts Immune System
By inhibiting the virus, ART enables the immune system to heal. This signifies an increase in CD4 cells, which are white blood cells required to combat infections. A robust immune system aids HIV patients in remaining healthy and fighting off diseases.
Reduces Illness Risk
HIV patients with a regulated viral load and a strengthened immune system are considerably less likely to acquire serious illnesses such as pneumonia or tuberculosis, sometimes known as opportunistic infections.
Prevents HIV Transmission
When a patient's viral load is regularly undetectable due to successful ART, the risk of transferring HIV to others via intercourse is extremely low. This is a significant advancement in HIV prevention.
Improves Overall Health
Effective HIV management with ART enables patients to live longer, healthier lives. They have better overall health and live a higher quality of life. In brief, antiretroviral therapy (ART) is a game changer for HIV patients. It is not a cure, but it efficiently regulates the virus, maintains the immune system, and enables HIV patients to lead full and productive lives.
Extended Lifespan
People living with HIV can expect to live a nearly normal life if they receive adequate ART. Early diagnosis and ART initiation are critical for realising these benefits. ART enables people with HIV to live long, productive lives and plan for the future.
Prevention of AIDS
Untreated HIV infection can lead to AIDS, a state in which the immune system is severely impaired. ART greatly lowers the risk of contracting AIDS and its complications, allowing people to enjoy healthier lives.
Mental Health Benefits
Living with HIV can be stressful, but ART can help to improve mental health by reducing anxiety about disease progression and transmission. Individuals can experience a greater sense of well-being and hope for the future when their prognosis improves.
In essence, ART is a life-changing treatment for HIV patients. It enables people to effectively manage their illness, live long, healthy, and satisfying lives, and make meaningful contributions to society.
Conclusion
Antiretroviral Therapy (ART) has transformed the treatment of HIV infection. By targeting several stages of the HIV replication cycle, ART successfully suppresses the virus, allowing the immune system to recover and combat infections. This results into a number of advantages for persons living with HIV. Reduced viral load improves overall health and reduces the incidence of opportunistic illnesses. ART greatly reduces the chance of contracting AIDS and its complications. People with HIV can expect to live a nearly normal life with successful ART, allowing them to plan for the future. The risk of transmitting HIV through sex is exceedingly minimal due to undetectable viral load resulting from persistent ART therapy. By managing the infection and minimizing consequences, ART allows people to live fuller lives with more energy and a better capacity to participate in daily activities. While ART does not cure HIV, it helps reduce it from a life-threatening sickness to a tolerable chronic condition. Continued ART research focuses on producing more effective drugs with fewer adverse effects, investigating long-acting solutions for better adherence, and, finally, finding a cure. With continued advances in ART, the future for HIV patients looks brighter than ever.
References
- Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015; 517: 381-385.
- Brodin J, Zanini F, Thebo L, Lanz C, Bratt G, Neher RA, et al. Establishment and stability of the latent HIV-1 DNA reservoir. eLife. 2016; 5.
- Bullen CK, Laird GM, Durand CM, Siliciano JD, Siliciano RF. New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nature Medicine. 2014; 20: 425-429.
- Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS. 2014; 28: 1579-1591.
- Currier JS, Lundgren JD, Carr A, Klein D, Sabin CA, Sax PE, Schouten JT, Smieja M. Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy. Circulation. 2008; 118.
- Klein D, Hurley LB, Quesenberry CP, Sidney S. Do Protease Inhibitors Increase the Risk for Coronary Heart Disease in Patients With HIV-1 Infection?. J Acquired Immune Deficiency Syndromes. 2002; 30: 471-477.
- Spreen WR, Margolis DA, Pottage JC. Long-acting injectable antiretrovirals for HIV treatment and prevention. Current Opinion in HIV and AIDS. 2013; 8: 565-571.
- Ullrich R, Zeitz M, Heise W, Lage M, Hoffken G, Riecken EO. Small Intestinal Structure and Function in Patients Infected with Human Immunodeficiency Virus (HIV): Evidence for HIV-Induced Enteropathy. Annals of Internal Medicine. 1989; 111: 15.
- Wallet MA, Rodriguez CA, Yin L, Saporta S, Chinratanapisit S, Hou W, et al. Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS. 2010; 24: 1281-1290.
- Yukl SA, Kaiser P, Kim P, Telwatte S, Joshi SK, Vu M, et al. HIV latency in isolated patient CD4+T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Science Translational Medicine. 2018; 10.
- Terblanche LM, Stellenberg EL. Patient knowledge of HIV and its treatment in South Africa. African J Primary Health Care and Family Medicine. 2014; 6.
- Ruud KW, Srinivas SC, Toverud EL. Knowledge of HIV and its treatment among health care providers in South Africa. Int J Clinical Pharmacy. 2013; 36: 352-359.
- Carpenter CCJ, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, et al. Antiretroviral Therapy for HIV Infection in 1998. JAMA. 1998; 280: 78.
- Carpenter CCJ. Antiretroviral Therapy for HIV Infection in 1997. JAMA. 1997; 277: 1962-1969.
- Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. New England J Medicine. 2015; 373: 795-807.
- Kleihues P, Leib SL, Strittmatter C, Wiestler OD, Lang W. HIV Encephalopathy: Incidence, Definition and Pathogenesis. Acta Pathologica Japonica. 1991; 41: 197-205.
- Xu JP, Francis AC, Meuser ME, Mankowski M, Ptak RG, Rashad AA, et al. Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action. PubMed. 2018; 5: 1070.
- Malim MH and Bieniasz PD. HIV Restriction Factors and Mechanisms of Evasion. Cold Spring Harbor Perspectives in Medicine. 2012; 2: a006940.
- Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, Hughes SH, et al. Structure and Function of HIV-1 Reverse Transcriptase: Molecular Mechanisms of Polymerization and Inhibition. J Molecular Biology. 2009; 385: 693-713.
- Leserman J. HIV disease progression: depression, stress, and possible mechanisms. Biological Psychiatry. 2003; 54: 295-306.
- Fauci AS. Immunopathogenic Mechanisms of HIV Infection. Annals of Internal Medicine. 1996; 124: 654.
- Engelman A, Mizuuchi K, Craigie HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer. Cell. 1991; 67: 1211-1221.
- Moir S, Chu TW, Fauci AS. Pathogenic Mechanisms of HIV Disease. Annual Review of Pathology. 2011; 6: 223-248.
- Ivanov AV, Valuev-Elliston VT, Ivanova ON, Kochetkov SN, Starodubova ES, Bartosch B, et al. Oxidative Stress during HIV Infection: Mechanisms and Consequences. Oxidative Medicine and Cellular Longevity. 2016; 1-18.
- Heaton R, Clifford D, Franklin Woods S, Ake C, Vaida F, Ellis R, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology. 2010; 75: 2087-2096.
- Palella FJ, Deloria-Knoll M, Chmiel JS, Moorman AC, Wood KC, Greenberg AE, et al. Survival Benefit of Initiating Antiretroviral Therapy in HIV-Infected Persons in Different CD4+ Cell Strata. Annals of Internal Medicine. 2003; 138: 620.
- Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirology 2002; 8: 136-142.
- Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018; 561: 479-484.
- Vanable PA, Ostrow DG, McKirnan DJ, Taywaditep KJ, Hope BA. Impact of combination therapies on HIV risk perceptions and sexual risk among HIV-positive and HIV-negative gay and bisexual men. Health Psychology. 2000; 19: 134.
- Elford J, Bolding G, Maguire M, Sherr L. Combination Therapies for HIV and Sexual Risk Behavior among Gay Men. J Acquired Immune Deficiency Syndromes. 2000; 23: 266-271.
- Chancellor JV, Hill AM, Sabin CA, Simpson KN, Youle M. Modelling the Cost Effectiveness of Lamivudine/Zidovudine Combination Therapy in HIV Infection. PharmacoEconomics. 1997; 12: 54-66.
- Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature. 2012; 492: 118-122.
- Moore RD, Chaisson RE. Natural history of HIV infection in the era of combination antiretroviral therapy. AIDS. 1999; 13: 1933-1942.
- Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, et al. Virologic and Immunologic Consequences of Discontinuing Combination Antiretroviral-Drug Therapy in HIV-Infected Patients with Detectable Viremia. New England J Medicine. 2001; 344: 472-480.
- Chesney MA, Morin M, Sherr L. Adherence to HIV combination therapy. Social Science and Medicine. 2000; 50: 1599-1605.
- Freedberg KA, Losina E, Weinstein MC, Paltiel AD, Cohen CJ, Seage GR, et al. The Cost Effectiveness of Combination Antiretroviral Therapy for HIV Disease. New England J Medicine. 2001; 344: 824-831.
- Kalichman SC, Ramachandran B, Catz S. Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J General Internal Medicine. 1999; 14: 267-273.
- Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, et al. Quantifying Residual HIV-1 Replication in Patients Receiving Combination Antiretroviral Therapy. New England J Medicine. 1999; 340: 1605-1613.
- Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Medicine. 1999; 5: 512-517.
- Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997; 387: 188-191.
- Chinese guidelines for diagnosis and treatment of HIV/AIDS. PubMed. 2021; 60: 1106-1128.
- Kanters S, Socias ME, Paton NI, Vitoria M, Doherty M, Ayers D, et al. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network mmeta-analysis.the Lancet. HIV. 2017; 4: e433-e441.
- Bruce RD, Kresina TF, McCance-Katz EF. Medication-assisted treatment and HIV/AIDS: aspects in treating HIV-infected drug users. AIDS. 2010; 24: 331-340.
- Etienne M, Hossain M, Redfield R, Stafford K, Amoroso A. Indicators of Adherence to Antiretroviral Therapy Treatment among HIV/AIDS Patients in 5 African Countries. J Int Association of Physicians in AIDS Care. 2010: 9: 98-103.
- Rosen S, Ketlhapile M, Sanne I, DeSilva MB. Cost to patients of obtaining treatment for HIV/AIDS in South Africa. PubMed. 2007; 97: 524-529.
- Taha H, Das A, Das S. Clinical effectiveness of dolutegravir in the treatment of HIV/AIDS. Infection and Drug Resistance. 2015: 339.
- Besednova NN, Zvyagintseva TN, Kuznetsova TA, Makarenkova ID, Smolina TP, Fedyanina LN, et al. Marine Algae Metabolites as Promising Therapeutics for the Prevention and Treatment of HIV/AIDS. Metabolites. 2019; 9: 87.
- Voshavar C. Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges. Current Topics in Medicinal Chemistry. 2019; 19: 1571-1598.
- Tran BX. Quality of Life Outcomes of Antiretroviral Treatment for HIV/AIDS Patients in Vietnam. PloS One. 2012; 7: e41062.
- Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ. British Medical J. 2009; 338: a3172.
- Ebrahim SH, Anderson JE, Weidle P, Purcell DW. Race/Ethnic Disparities in HIV Testing and Knowledge About Treatment for HIV/AIDS: United States. 2001. AIDS Patient Care and STDs. 2004; 18: 27-33.
- Okosun K, Makinde O, Takaidza I. Impact of optimal control on the treatment of HIV/AIDS and screening of unaware infectives. Applied Mathematical Modelling. 2013; 37: 3802-3820.
- Ghosh AK, Osswald HL, Prato G. Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS. J Medicinal Chemistry. 2016; 59: 5172-5208.
- Peek ST, Luijkx KG, Rijnaard MD, Nieboer ME, Van Der Voort CS, Aarts S, et al. Older Adults’ Reasons for Using Technology while Aging in Place. Gerontology. 2015; 62: 226-237.
- Kleihues P, Leib SL, Strittmatter C, Wiestler OD, Lang W. HIV Encephalopathy: Incidence, Definition and Pathogenesis. Acta Pathologica Japonica. 1991b; 41: 197-205.
- Weiss RA. How Does HIV Cause AIDS?. Science. 1993; 260: 1273-1279.
- Idele P, Gillespie A, Porth T, Suzuki C, Mahy M, Kasedde S, Luo C. Epidemiology of HIV and AIDS Among Adolescents. J Acquired Immune Deficiency Syndromes. 2014; 66: S144-S153.
- Fauci AS. HIV and AIDS: 20 years of science. Nature Medicine. 2003; 9: 839-843.
- Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013; 382: 1525-1533.