In recent years, an HIV diagnosis is no longer a death sentence, thanks to the remarkable progress in medical advancements. However, despite the availability of powerful medications, HIV remains a formidable global public health threat. In 2022 alone, there were 1.3 million new infections and nearly half as many deaths.
As the number of people living with HIV continues to grow, sustained efforts in testing, treatment, and prevention become crucial to prevent a potential rebound in new infections. This article delves into the comprehensive strategies, goals, and challenges outlined by a United Nations program aimed at reducing new HIV infections and AIDS-related deaths, with the ultimate goal of ending the epidemic by 2030.
Historical Progress and Current Treatment Landscape
The journey from the approval of the first HIV treatment, AZT (azidothymidine), in 1987 to the present day has witnessed significant advancements. The introduction of combination antiretroviral therapy (ART) in 1996 marked a turning point, transforming HIV into a manageable chronic condition. Today, ART disrupts HIV replication and invasion of immune cells, achieving viral suppression and preventing transmission. Dr. Monica Gandhi, director of the University of California, San Francisco Center for AIDS Research, emphasizes the continuous improvement in treatment efficacy since 1996.
TABLE 1 – Antiretroviral therapy (ART)
Antiretroviral therapy (ART) is a medical intervention designed to manage and treat infections caused by the human immunodeficiency virus (HIV). HIV is a retrovirus that attacks the immune system, specifically the CD4 cells (T cells), which play a crucial role in the immune response.
Mechanism of Action:
- Targeting Viral Replication: ART consists of a combination of different classes of antiretroviral drugs that target various stages of the HIV life cycle. These classes include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and entry inhibitors.
- Blocking Reverse Transcription: NRTIs and NNRTIs interfere with the reverse transcription process, where viral RNA is transcribed into DNA by the enzyme reverse transcriptase. NRTIs act as faulty building blocks, causing premature termination of the DNA chain, while NNRTIs bind directly to reverse transcriptase, inhibiting its function.
- Disrupting Integration: INSTIs prevent the integration of viral DNA into the host cell’s genome by inhibiting the activity of the enzyme integrase. This step is essential for the virus to become a permanent part of the host cell and replicate.
- Inhibiting Viral Maturation: Protease inhibitors block the activity of the HIV protease enzyme, preventing the cleavage of viral polyproteins into functional, mature proteins. This step is crucial for the assembly of new viral particles.
Goals of Antiretroviral Therapy:
- Viral Suppression: The primary goal of ART is to achieve and maintain an undetectable viral load, meaning that the amount of HIV in the blood is so low that it cannot be detected by standard tests. This helps preserve immune function and prevent the progression to AIDS.
- Immune System Preservation: By suppressing viral replication, ART allows the immune system to recover and rebuild CD4 cell counts. This helps the body defend itself against opportunistic infections and other complications associated with advanced HIV disease.
- Preventing Transmission: Effective ART not only benefits the individual but also reduces the risk of transmitting the virus to others. When the viral load is undetectable, the likelihood of HIV transmission through sexual contact or from mother to child during childbirth is significantly reduced.
Treatment Guidelines:
- Initiation of Treatment: The decision to start ART is based on various factors, including CD4 cell counts, viral load, clinical symptoms, and overall health. Recent guidelines often recommend early initiation of treatment, regardless of CD4 count, to maximize the benefits of therapy.
- Adherence to Medication: ART requires strict adherence to the prescribed medication regimen. Missing doses or not taking medications as directed can lead to the development of drug-resistant strains of HIV and treatment failure.
- Regular Monitoring: Patients on ART undergo regular monitoring, including viral load tests, CD4 cell counts, and assessments of overall health. This monitoring helps healthcare providers assess treatment effectiveness and make adjustments if necessary.
- Management of Side Effects: Antiretroviral drugs can have side effects, ranging from mild to severe. Healthcare providers work closely with patients to manage side effects and, if necessary, adjust the treatment regimen to minimize adverse reactions.
Challenges and Considerations:
- Drug Resistance: HIV has a high mutation rate, leading to the development of drug-resistant strains. Regular monitoring of viral load and early intervention with alternative drug combinations help manage drug resistance.
- Access to Treatment: Despite advances in HIV treatment, access to ART remains a challenge in many parts of the world. Economic, social, and healthcare system factors contribute to disparities in treatment availability.
- Long-Term Health: The long-term effects of ART are a topic of ongoing research. Some concerns include potential cardiovascular and metabolic effects, as well as the impact of prolonged treatment on organ systems.
- Cure Research: While ART effectively manages HIV, it does not cure the infection. Intensive research is ongoing to develop strategies for curing HIV, including gene therapies and immunotherapies.
Goals and Targets for 2030
A global effort under the United Nations program seeks to reduce new HIV infections and AIDS-related deaths dramatically by 2030. The program’s ambitious goal is to bring the rate of new infections and deaths below the reproductive rate of 1, ensuring that each person living with HIV infects fewer than one other person in their lifetime.
Challenges and Targets
To achieve the program’s goals, the “95-95-95” target for 2025 is crucial. This target aims for 95% of people with HIV to know their status, 95% of those diagnosed to take HIV drugs, and 95% of those treated to achieve viral suppression. However, the latest UNAIDS report for 2022 reveals that only 76% of the 39 million people with HIV worldwide were taking ART, and 71% were virally suppressed. Closing this gap necessitates addressing challenges such as reaching vulnerable populations, particularly children, and improving prevention and testing for teen girls and young women.
Vulnerable Populations: Children and Teen Girls
In 2022, only 57% of the 1.5 million children under 15 with HIV received treatment. Challenges include limited child-friendly formulations and the absence of long-acting ART options for children under 12. Efforts to integrate pediatric care with family-focused services are crucial. Similarly, prevention and testing for teen girls and young women, who face unique socio-economic challenges, must be improved through discreet prevention services, sex education, and access to effective tools like cabotegravir.
Other At-Risk Populations
Several at-risk populations, including transgender people, men who have sex with men, sex workers, and people who inject drugs, lag behind the targets. Discriminatory policies, social taboos, and legal barriers hinder access to HIV care. Addressing these challenges requires lifting discriminatory policies, integrating HIV care into community-based programs, and ensuring access to preventive measures.
Access to Treatment and Cost Barriers
While there has been a significant increase in the number of people taking pre-exposure prophylaxis (PrEP) pills, cost remains a barrier for widely adopting cabotegravir, a potential game-changer. Expanding access to affordable medications and routine viral-load testing, alongside addressing socio-economic factors contributing to treatment interruptions, is crucial.
TABLE 2 – Pre-exposure prophylaxis (PrEP) pills
Pre-exposure prophylaxis (PrEP) is a biomedical HIV prevention strategy that involves the use of antiretroviral drugs by individuals who are at a high risk of acquiring the human immunodeficiency virus (HIV). The goal of PrEP is to prevent the establishment of HIV infection in individuals who are HIV-negative but are at substantial risk of exposure.
In this detailed explanation, we will delve into various aspects of PrEP, including its mechanism of action, efficacy, considerations for use, and ongoing research.
Mechanism of Action:
- Antiretroviral Drugs Used in PrEP: The primary drugs used in PrEP are tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). These drugs are nucleoside reverse transcriptase inhibitors (NRTIs) and are also components of some antiretroviral therapy (ART) regimens used to treat HIV. In PrEP, they work by inhibiting the reverse transcriptase enzyme, which is essential for the replication of HIV.
- Preventing Viral Replication: PrEP pills, when taken consistently, help maintain a constant level of the antiretroviral drugs in the bloodstream. This prevents HIV from establishing itself in the body by blocking the early stages of viral replication, specifically the conversion of viral RNA into DNA.
- Site of Action: The drugs in PrEP primarily target mucosal tissues, especially in the genital and rectal areas, which are common sites of HIV entry. By creating a barrier at these sites, PrEP reduces the risk of HIV transmission.
Efficacy:
- Clinical Trials: The efficacy of PrEP has been demonstrated in several landmark clinical trials, including the iPrEx study, Partners PrEP, and the TDF2 trial. These studies showed that consistent use of PrEP reduced the risk of HIV acquisition by a significant margin in diverse populations, including men who have sex with men (MSM), heterosexual couples, and injection drug users.
- High Levels of Adherence: The effectiveness of PrEP is closely tied to adherence. Studies indicate that individuals who take PrEP consistently as prescribed have a high level of protection against HIV acquisition. Regular medical check-ups and monitoring are essential to ensure adherence and detect any potential side effects.
Considerations for Use:
- Risk Assessment: PrEP is recommended for individuals at substantial risk of HIV infection. This includes individuals in serodiscordant relationships (where one partner is HIV-positive and the other is not), MSM, transgender individuals, and people who engage in high-risk behaviors such as injection drug use.
- Prescription and Monitoring: PrEP is available only by prescription, and its use requires regular medical monitoring. Before prescribing PrEP, healthcare providers conduct thorough assessments of HIV risk, kidney function, and sexually transmitted infections. Regular HIV testing is also performed to ensure ongoing HIV negativity.
- Adherence Counseling: Effective use of PrEP involves adherence counseling to promote consistent pill-taking. Healthcare providers discuss the importance of taking PrEP daily, potential side effects, and strategies to overcome barriers to adherence.
- Sexual Health Services: PrEP is often integrated with sexual health services, including counseling on safer sex practices, condom use, and testing for other sexually transmitted infections.
Ongoing Research and Developments:
- New PrEP Formulations: Research is ongoing to develop alternative formulations of PrEP, such as long-acting injectables or implants, to address issues related to daily pill adherence.
- Resistance and Breakthrough Infections: Studies continue to explore instances of breakthrough infections in individuals taking PrEP and the development of drug resistance. Understanding these occurrences is crucial for optimizing PrEP guidelines and strategies.
- Expanding Access: Efforts are underway to expand access to PrEP globally. This includes addressing issues of affordability, awareness, and stigma, particularly in regions with high HIV prevalence.
- PrEP for Different Populations: Research is exploring the use of PrEP in diverse populations, such as adolescent populations, transgender individuals, and pregnant or breastfeeding women, to understand its safety and efficacy in these groups.
Success Stories and Ongoing Challenges
Several countries, including Botswana, Eswatini, Rwanda, the United Republic of Tanzania, and Zimbabwe, have already achieved the 95-95-95 target. However, the U.S. and Eastern Europe still face challenges due to factors like systemic inequalities, stigma, and limited access to care.
Beyond 2030
While progress has been made in transforming HIV into a manageable chronic disease, the quest for an HIV vaccine and cure remains essential. Investments in research and development continue to be crucial for achieving the ultimate goal of eradicating HIV.
Conclusion
The global fight against HIV requires a multifaceted approach, addressing challenges in treatment access, testing, and prevention. The UN program’s goals, if achieved, could bring us closer to ending the HIV epidemic by 2030. Success hinges on bridging gaps in vulnerable populations, improving access to innovative treatments, and dismantling societal barriers that impede progress. The journey toward eradicating HIV is challenging, but with sustained efforts, it is an achievable goal that would transform the virus into a manageable health condition for individuals worldwide.
