Have you ever thought of complications associated with the drugs we take to tackle an infection?

World report: Detected HIV infection

India is not far behind

The devastating impact of HIV is evident in the alarming situation in Tripura, where 47 students have tragically lost their lives to the infection, and 828 have tested positive, underscoring the severe, lifelong consequences of this disease. This stark reminder of the ongoing threat of HIV highlights the critical need for awareness, prevention, and effective treatment strategies.

WHO Report on Current HIV Therapeutic Regime

ART Drugs: The Current Therapeutic Regime and Its Long-Term Side Effects

Antiretroviral therapy (ART) has been the cornerstone of HIV treatment, transforming what was once a fatal diagnosis into a manageable chronic condition. However, this life-saving regimen is not without its challenges. Over time, patients on ART may experience a range of side effects, from metabolic disturbances to cardiovascular issues, and even increased inflammation in various tissues. Let’s dive into each of these side effects in detail:

Side effects	Mechanisms of ART-Induced Complications	Drugs That Trigger Clinical Complications	References
Bone Density Loss	Some ART drugs directly impact bone cells by increasing osteoclast activity, increasing bone resorption, and reducing bone mineral density (BMD). ART causes a reduction in vitamin D levels, which are essential for calcium absorption and bone health.	Tenofovir Alafenamide (TAF) Abacavir Efavirenz: HIV RT inhibitor	Biver. et.al2022
Neuropsychiatric Effects	Dolutegravir downregulates folate transporters and induces brain inflammation, causing neuropsychiatric side effects. While the exact mechanisms of Efavirenz and Elvitegravir are unclear, both have been linked to similar side effects in patient studies	Elvitegravir: HIV integrase enzyme inhibitor Dolutegravir: HIV integrase enzyme inhibitor Efavirenz: HIV RT inhibitor	Huang. et.al.2024, Zhang .et.al2023
Liver and Kidney Toxicity	ART drugs like EFV, AZT, and ddI cause oxidative stress and mitochondrial dysfunction by inhibiting mitochondrial DNA synthesis, leading to liver cell damage. Nevirapine can trigger immune-mediated hepatotoxicity, causing inflammation and hepatitis, while protease inhibitors can cause metabolic disturbances, resulting in lipid accumulation in liver cells and potentially progressing to steatosis, NAFLD, fibrosis, and cirrhosis.	Efavirenz: RT inhibitor Nevirapine: RT inhibitor Protease Inhibitors (PIs) like Ritonavir and Atazanavir Zidovudine: NRTI Didanosine: NRTI
Lipid Abnormalities / Lipodystrophy	Immune cells in adipose tissue, including macrophages and T cells, play a crucial role in its function. In PLWH, a pro-inflammatory shift, exacerbated by ART, leads to adipose tissue dysfunction, chronic inflammation, and long-term metabolic complications	Thymidine analogue nucleoside reverse transcriptase inhibitors eg: zidovudine and stavudine Protease inhibitors: indinavir and full-dose ritonavir Alternate new ART drugs: tenofovir disoproxil fumarate and emtricitabine	Koethe. et.al.2020

However, the future holds promise

The development of effective vaccines against HIV is underway, aiming to prevent new infections and reduce the global burden of the disease. These advancements signal a potential shift from managing HIV to possibly curing and preventing it, marking a new era in the fight against this virus.

Video link: https://www.hiv.gov/hiv-basics/hiv-prevention/potential-future-options/hiv-vaccines

Cutting-edge research is now exploring advanced techniques such as CRISPR-Cas9 to target and potentially eradicate the integrated HIV genome, offering hope for a cure.

Video link: https://www.umassmed.edu/news/news-archives/2015/04/editing-hiv-out-of-our-genome-with-crispr/

References

1. Koethe, J.R. et al. (2020) ‘HIV and antiretroviral therapy-related fat alterations’, Nature Reviews Disease Primers, 6(1). doi:10.1038/s41572-020-0181-1.

2. Biver, E. (2022). Osteoporosis and HIV Infection. Calcified Tissue International, 110(5), pp.624–640. doi:https://doi.org/10.1007/s00223-022-00946-4.

3. Huang, C., Md. Tozammel Hoque, Qing Rui Qu, Henderson, J. and Bendayan, R. (2024). Antiretroviral drug dolutegravir induces inflammation at the mouse brain barriers. The FASEB Journal, 38(13). doi:https://doi.org/10.1096/fj.202400558r.

4. Zhang, W., Wang, Y., Li, E., Yan, D., Yu, J., Zhu, M., Shi, J. and Zheng, L. (2023). Neuropsychiatric Adverse Events Following Antiretroviral Therapy in People Living with HIV: A Real-World Study of Dynamic Trends and Risk Factors in Hangzhou, China. Infection and Drug Resistance, Volume 16, pp.5007–5019. doi:https://doi.org/10.2147/idr.s419308.

5. Gatch, M. B., Kozlenkov, A., Huang, R. Q., Yang, W., Nguyen, J. D., González-Maeso, J., & Dillon, G. H. (2013). The HIV antiretroviral drug efavirenz has LSD-like properties. Neuropsychopharmacology, 38(12), 2373-2384.

6. Mukonzo, J. K., Okwera, A., Nakwagala, F. N., Sabin, C. A., Bunn, J. E., Waako, P., & Owen, A. (2008). Pharmacokinetics of efavirenz influences susceptibility to malaria: a new paradigm for antimalarial therapy. Journal of Infectious Diseases, 198(2), 208-214.

7. Stern, J. O., Robinson, P. A., Love, J., Lanes, S., Imperiale, M. S., Mayers, D. L., & Johnson, M. (2003). A comprehensive hepatic safety analysis of nevirapine in different populations of HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes, 34(Suppl 1), S21-S33.

8. Stern, J. O., Robinson, P. A., Love, J., Lanes, S., Imperiale, M. S., Mayers, D. L., & Johnson, M. (2003). A comprehensive hepatic safety analysis of nevirapine in different populations of HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes, 34(Suppl 1), S21-S33.

9. Martin, J. L., Brown, A. J., Matthews, D. J., & Johnson, M. A. (1995). Mitochondrial toxicity of antiviral drugs. Nature Medicine, 1(5), 417-422

‌

‌

‌