The Principles of Therapy for HIV-1 Infection
Thomas R. O’Brien in Chemokine Receptors and AIDS, 2019
Drug toxicity is another major reason for alteration of therapeutic regimens. The major adverse effects that are associated with current antiretroviral drugs include mitochondrial toxicity, lipodystrophy, and hypersensitivity (see reference 58 for a review). Adverse effects thought to be related to mitochondrial toxicity are common with NRTIs and range in severity from mild to life threatening. These conditions include myopathy, neuropathy, hepatic steatosis, pancreatitis, and lactic acidosis. The prevalence and severity of these conditions are related to the duration of therapy, and both the rate and frequency of recovery varies by condition. These effects are thought to be caused by inhibition of the mitochodrial DNA polymerase y and resultant impaired synthesis of mitochondrial enzymes that generate ATP by oxidative posphorylation, but the conditions are, nonetheless, somewhat drug specific. Estimates of the frequency of NRTI-associated peripheral neuropathy (mainly due to ddl, d4T, and ddC) range up to 30%, but hepatic and pancreatic complications are less frequent. There are currently no assays that can predict who will develop these mitochondrial toxicities.
Role of Nanostructures in Inhibition and Treatment of Viral Infections
Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji in Viral and Antiviral Nanomaterials, 2022
Human immunodeficiency virus (HIV) is the source organism causing acquired immunodeficiency syndrome (AIDS), which is the main public health issue and cause of many deaths worldwide (Fauci et al. 2013). Yet there is no effective vaccine against HIV, due to its atypical pathogenesis. Studies for antiretroviral drugs against the infection were of great concern; currently, only 29 drugs have been approved based on their replication phases. However, due to their toxicity, systemic side effects, efficient concentrations in the viral pool, drug-drug interaction, poor patient acquiescence, and poor bioavailability, antiretroviral drugs have not been used as potential actions. So, to prevail over these problems, nanoformulation approaches have been developed in recent decades; a few are listed in Table 5.2. Some other nanoformulations are polyanionic carbosilane dendrimers (PCDs), used as topical microbicides; their mode of action is that they inhibit entry of the virus by fusion process (Telwatte et al. 2011). Tenofovir and maraviroc, in mixture with PCDs, are shown to have high efficacy as monotherapy; the combination decreases side effects and the number of doses needed, and also reduced the appearance of multidrug-resistant mutants of HIV (Sepulveda-Crespo et al. 2015).
AIDS-related malignancy
Pat Price, Karol Sikora in Treatment of Cancer, 2014
HIV infection causes immunosuppression, CD4 lymphocyte count loss and a progressive risk of opportunistic infection and tumours. Similarly, chemotherapy and radiotherapy for HIV-related malignancies is associated with an increased risk of infection secondary to the myelosuppression and additional CD4 lymphocyte count loss.71–73 The risk of infection is further raised by the presence of central venous catheters,74–77 neutropenia associated with HIV infection78,79 and many of the therapies utilized to treat HIV and its complications.80–82 These factors all combine to produce a significant risk of opportunistic infection in PLWH undergoing treatment for cancer. Guidelines for the initiation of opportunistic infection prophylaxis and cART are available,83 but these treatments should be started at higher CD4 cell counts in patients who are to undergo chemotherapy and radiotherapy. Patients treated with chemotherapy for NHL should receive antimicrobial prophylaxis including acyclovir, azithromycin, co-trimoxazole and fluconazole. There are significant and important pharmacokinetic interactions between antiretroviral drugs and cytotoxic chemotherapy agents, and treating physicians need to pay careful attention to these. For example, ritonavir-boosted protease inhibitors markedly potentiate the myelotoxicity of anthracyclines as a consequence of microsomal enzyme inhibition reducing the metabolism of anthracyclines.84
A literature review of the patent application publications on cabotegravir – an HIV integrase strand transfer inhibitor
Published in Expert Opinion on Therapeutic Patents, 2020
At this time, the cure for HIV/AIDS does not yet exist and therefore, the main purpose of antiretroviral drugs is to control progression of the illness through long-term inhibition of HIV replication [2]. The life quality and life expectancy of HIV-infected patients has been drastically improved by the arrival of highly active antiretroviral therapy. Currently, more than 30 antiretroviral drugs from seven mechanistic classes and multiple effective first-line treatments for HIV-1 treatment are known [3]. Current combined antiretroviral treatments (cART) are very potent and well tolerated [4], therefore having exceptional rates of virologic suppression. However, in order to maintain suppression of the virus, as well as to avoid emergence of the drug resistance and to reduce the risk of HIV transmission, strict adherence to daily antiretroviral therapy is crucial [5]. Complete elimination of HIV is currently not possible; medications must be taken permanently to maintain the virus under suppression. In this aspect, different approaches to antiretroviral treatment in the near future are needed to improve patient compliance and to reduce risk of the drug resistance emergence.
“There is a chain of connections”: using syndemics theory to understand HIV treatment side effects
Published in AIDS Care, 2018
An important outcome of our analysis is that side effects can act as a syndemic risk factor by making PLWH more susceptible to mental health issues (particularly depression), drug use and co-morbidities. Throughout the interviews, participants spoke at great length about the relationship between side effects and depression. They recognized that depression could be a side effect but for the majority, depression was a combination of the effects of antiretroviral drugs and a direct outcome of experiencing the physical, psychological, social, and economic burden of side effects – combined with the feeling of being sick and dealing with the daily reminder of being HIV-positive (i.e., the pills). For this reason, many participants had been or were taking antidepressants at the time of the interview. Some had been or were in therapy (Informant 41 in Table 2).
Investigational drugs for HIV: trends, opportunities and key players
Published in Expert Opinion on Investigational Drugs, 2023
Ronald J. Overmars, Zoë Krullaars, Thibault Mesplède
Our review illustrates how long-acting antiretroviral drugs do not solve the issue of treatment adherence. As much as people can fail to take their daily oral treatment for multiple reasons, they can also miss their appointment for an injection. Episodically forgotten oral dosing is usually rapidly self-corrected and without consequence on treatment outcome or health, as evidenced by intermittent drug scheduling [89], which we do not endorse. How missed injections should be managed is still being worked out. Typically, injections have a 7-day recommended window for administration. In the future, we hope self-administration will help prevent or mitigate such misadventures. The current strategy to deal with missed timely injections is to provide ‘in-pocket’ oral antiretroviral drugs.
Related Knowledge Centers
- Antiviral Drug
- Drug Resistance
- Opportunistic Infection
- Retrovirus
- Immune System
- HIV/AIDS
- HIV
- Serodiscordant
- Entry Inhibitor
- Maraviroc