Clarithromycin Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing
Drugs That Prevent Opportunistic Infections In HIV
When you have HIV/AIDS, you're at higher risk of infections your body would normally be able to fight off. They can also be more severe, more frequent, or both. These infections are called opportunistic infections.
The risks are higher if you have very low levels of CD4 T cells. These are white blood cells that fight infection. The more severe your HIV infection, the lower your CD4 levels get, and the weaker your immune response to invaders. If your CD4 cells drop below 200, that means your HIV infection has progressed to the most severe phase called AIDS.
Fortunately, with the rise of antiretroviral therapy (ART) for HIV in the 1990s, opportunistic infections have gone down significantly. ART does a very good job of getting your CD4 levels back up. But some people may not respond well to ART and need additional protection from infection. And some germs and viruses find ways to cause infection even when you have high CD4 counts.
The most important things you can do to prevent opportunistic infections are to:
Your doctors may recommend additional treatments to help shield you from opportunistic infections, as well.
This is the first line of treatment for HIV and the No. 1 way to prevent opportunistic infections. Infections can happen in people who are getting ART, but it happens mostly in people who aren't.
If you're diagnosed with HIV early, when your CD4 count is still high, and you start ART right away, it's possible that you'll never develop an opportunistic infection.
If you're diagnosed with HIV later, after the disease has already weakened your immune system, and you go to the doctor with an opportunistic infection, you'll start taking medicine to fight the opportunistic infection right away. When you should start your ART regimen, however, depends on what opportunistic infection you have.
You can start ART right away, or within 2 weeks of most opportunistic infections, including:
In advanced HIV, the combination of ART and treatment for the opportunistic infection may cause dangerous side effects. So, you may need to wait 2 to 4 weeks to start ART if you have:
In addition to protecting you by making your immune system stronger, some ART medicines also specifically work against other viruses. The ART drug tenofovir, for example, also works against hepatitis B virus (HBV). If you have both HIV and HBV, your ART regimen may include tenofovir.
While ART is the most effective way to protect yourself, it's not a cure. Even after years of ART, after your CD4 levels have bounced back, your immune system remains affected by HIV. That's why it's important to know about other ways to prevent opportunistic infections.
Everyone with HIV should be screened for some opportunistic infections. You may need additional screenings if you've been exposed to certain infections (such as tuberculosis or sexually transmitted infections) or live in areas where some infections are more common.
Your doctor may screen you for:
It's especially important for people with chronic conditions like HIV to get all recommended vaccines, including COVID vaccines and a yearly flu shot. Respiratory diseases, such as pneumonia caused by pneumococcal bacteria, are especially common and dangerous to people with HIV. Pneumococcal disease can be prevented by vaccination. All people with HIV, if not already immune, should be vaccinated against hepatitis A and hepatitis B. A vaccine is now available to prevent shingles, which is caused by the same virus that causes chickenpox.
Take caution with live vaccines like MMR, chickenpox (not the same as the shingles vaccine), or the nasal spray vaccine for the flu. Live vaccines use a weakened form of a virus to give you immunity. When you have HIV, your body is at risk of getting an infection even with the weakened version of a virus. If your CD4 counts are high enough, these may be safe, but you'll need to talk with your doctor first.
HIV can weaken your body's response to vaccines, so early detection of HIV is key so that you can get vaccinated before your CD4 cell count drops too low.
Certain antibiotic medicines can be used to prevent some common opportunistic infections in people with HIV/AIDS.
However, your doctor will consider the risks and benefits of antibiotics for preventing infection in your situation. Antibiotics can lead to drug resistance, and they can disrupt the balance of the microbes in your gut, which can increase your risk for certain gastrointestinal infections.
Antibiotics to prevent tuberculosis (TB). Latent (inactive) TB infections are common and dangerous to someone diagnosed with HIV. As CD4 counts drop, a latent TB infection can reactivate.
A latent TB infection is diagnosed by a tuberculin skin test (TST, sometimes called a PPD) or by a blood test. Doctors often combine isoniazid and rifamycin antibiotics in a "drug cocktail" to prevent latent TB from turning into active TB. Your doctor may also start this treatment if you have been exposed to someone with active TB, even if you don't test positive for latent TB.
Rifamycin antibiotics can interfere with ART. If you're already on ART and are diagnosed with latent or active TB, your doctor may either change your ART drugs or use an alternative drug to treat your TB. Your doctor may need to tweak your regimen to make sure both treatments are working safely and effectively and monitor you to keep an eye on any toxic side effects. Rifamycin antibiotics can also lead to drug resistance fairly quickly, so you usually take them in combination with other drugs.
Trimethoprim-sulfamethoxazole (TMP-SMX). If your CD4 counts are below 200 cells, which means your HIV infection has progressed to AIDS, your doctor may use TMP-SMX to protect against a fungal pneumonia called pneumocystis pneumonia (PCP). You may also be advised to take TMP-SMX if you have a history of thrush, which is a fungal infection in your mouth and throat caused by the yeast candida albicans.
TMP-SMX also protects against lots of other diseases. These include:
If you've had PCP before, you may need to take TMP-SMX long-term to prevent it from coming back.
Some people have a bad reaction to TMP-SMX and need an alternative antibiotic medicine. Dapsone is a good alternative antibiotic for people allergic to TMP-SMX.
You will stay on TMP-SMX, or an alternative, until your CD4 levels go back up, and restart the medicine if they ever drop back down.
Antibiotics to prevent MAC. Germs from the Mycobacterium avium complex, or MAC, are related to the bacteria that causes tuberculosis. These germs are commonly found in soil, food, and water and are dangerous for people with weak immune systems.
MAC diseases happen in up to 40% of people with advanced HIV who are not taking ART. Preventing MAC disease is only recommended if you have a very low CD4 count (less than 50), aren't taking ART, or your ART is not working.
Antibiotic drugs used to prevent MAC disease include:
Your doctor will want to choose your drug regimens carefully. You will get this treatment until your CD4 counts go back up.
Immune globulins. If you haven't had chickenpox and you haven't been vaccinated for it, you may be given preventive medicines if you have contact with someone who has chickenpox. Your doctor will give you an immune globulin that can protect you after being exposed by directly giving you the antibodies against chickenpox. This is different from a vaccine, which uses pieces of a germ to make your body develop those antibodies itself.
Preventive drugs can be used in two key ways: preventing first-time infections (primary prophylaxis) and preventing infections from coming back (secondary prophylaxis).
In people with AIDS, serious fungal infections (like cryptococcal disease) or viral infections (like cytomegalovirus) often come back, so you may have to take secondary prophylaxis for a long time after an initial infection. This will depend on your CD4 count and the type of infection.
The herpes virus can also come back, so you may take "suppressive therapy" long term with an antiviral drug such as acyclovir or valacyclovir after a herpes infection.
Inhaled Amikacin Shows Promise For Untreated MAC Lung Infections
SAN DIEGO -- Adding amikacin liposome inhalation suspension (ALIS; Arikayce) to a macrolide-based regimen appeared to reduce respiratory symptoms and improve culture conversion rates in patients with newly diagnosed or recurrent Mycobacterium avium complex (MAC) lung infections, the randomized ARISE trial showed.
As measured by the nine-item Quality of Life-Bronchiectasis Respiratory Domain (QOL-B RD), 43.8% of patients in the ALIS arm achieved a meaningful improvement in symptoms from baseline to 7 months, as compared with 33.3% of those assigned to the macrolide-based regimen plus placebo, reported Charles Daley, MD, of National Jewish Health and the University of Colorado School of Medicine in Denver.
Culture conversion rates were numerically higher in the ALIS arm both following the 6-month period of daily treatment (80.6% vs 63.9% P=0.071) and at 7 months, a month after stopping treatment (78.8% vs 47.1%, nominal P=0.001), according to findings presented here at the American Thoracic Society annual meeting.
The main goal of the ARISE study was to validate patient-reported-outcome (PRO) tools using modern psychometric methods for key symptoms of MAC lung disease -- with respiratory symptoms and fatigue previously established as the most prevalent and bothersome to patients.
"It turns out there's no currently validated fit-for purpose PRO instrument for people with MAC lung disease," said Daley. "The symptoms that are most important to our patients are covered in two instruments" -- the QOL-B RD and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a.
Daley's presentation focused on the validation of the QOL-B RD (against the Patient Global Impression of Severity-Respiratory scale); the impact of ALIS on patients' respiratory symptoms using the QOL-B RD; and microbiologic outcomes with ALIS as part of a macrolide-based regimen for this patient population.
The QOL-B RD is a self-administered questionnaire with nine items to assess sputum, coughing, congestion, wheezing, chest pain, and other symptoms -- with eight of the items scored on a Likert Scale (a lot, a moderate amount, a little, not at all) and the sputum question requiring a descriptive answer.
Each score is standardized on a 0-100 scale, with 100 indicating no symptoms. Ultimately a 14.8-point change in an individual patient was deemed to be a meaningful difference on the QOL-B RD, said Daley.
While the study was not powered to show a significant difference between arms, the least-squares mean change from baseline to 7 months on the QOL-B RD favored the ALIS arm (12.24 vs 7.76, P=0.1073).
Results of the ARISE trial are "a significant step toward an area of unmet need in patients with non-cavitary [MAC lung disease]," said Sarah Taimur, MD, of the Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the study.
"It provides much-needed evidence for validation of a self-administered, patient-reported outcome measure that has been previously lacking in this patient population, and could serve as a critical tool that patients and their medical teams can use to gauge response to treatment," Taimur told MedPage Today.
ALIS is currently approved only for patients with MAC lung infections that do not respond to traditional treatments; the validated QOL-B RD instrument will help support the evaluation of the inhaled therapy in an ongoing phase III registrational study (ENCORE) testing a macrolide-based regimen plus either ALIS versus placebo in patients with newly diagnosed or recurrent MAC lung infections who have not received antibiotics for their current infection.
Daley presented findings from ARISE (Validation of Patient-Reported Outcome Measures in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex), which randomized 99 adults with newly diagnosed or recurrent MAC lung infections and non-cavitary disease who had not yet been treated with antibiotics for their current infection. Patients were enrolled at 76 sites across 15 countries, including the U.S.
All patients received azithromycin and ethambutol as their macrolide-based regimen and were randomized 1:1 to ALIS or an empty liposomal control (placebo) once daily for 6 months, followed by a month off of treatment for follow-up. All patients had a mean QOL-B RD score of 85 or less. Patients with mixed infections were allowed in the trial so long as MAC was the dominant species present.
Exclusion criteria included refractory or relapsed MAC infections, more than three previous MAC lung infections, prior ALIS exposure, a smoking history, and certain comorbidities (cystic fibrosis, prior lung transplant, active malignancy).
Participants had a median age of 67-72 years, three-fourths were women, and 81% were white. Most were enrolled from either North America (39%) or Europe (38%). Concurrent respiratory illnesses included bronchiectasis in 49%, asthma in 21%, chronic obstructive pulmonary disease in 16%, cough in 16%, and allergic rhinitis in 11%.
For 73% of the patients, this was their initial MAC infection. Overall, 32% had M. Avium infections, 43% had M. Intracellulare infections, and the rest had other or unspecified MAC infections.
Culture conversion was defined as no growth of MAC in sputum cultures on agar and broth media. Four sputum samples were collected from patients at each monthly visit during the study.
Patients in the ALIS arm achieved culture conversions a median 1 month earlier than those in the comparator arm. Overall, 12.8% of patients who achieved culture conversion in the ALIS arm experienced recurrence at any point in the study compared with 50% of those in the placebo arm. No patients in either group developed MAC isolates with resistance to ALIS.
Treatment-emergent adverse events (TEAEs) were reported in 92% of patients in the ALIS arm and 80% of those in the placebo arm, the most common of which included dysphonia (42% vs 4%, respectively), cough (27% vs 8%), diarrhea (27% vs 25%), and COVID-19 (13% vs 10%). Treatment discontinuation of ALIS specifically occurred in 19%, as compared with 6% with the placebo.
Serious TEAEs were reported in 15% of the ALIS arm and 6% of the comparator arm. No deaths were reported.
Adverse events of special interest included dizziness (4.2% in the ALIS arm vs 9.8% in the placebo arm), tinnitus (4.2% vs 7.8%, respectively), vertigo (4.2% vs 2%), deafness (2.1% vs 2%), dyspnea (10.4% vs 7.8%) or dyspnea on exertion (2.1% vs none), wheezing (6% vs none), hemoptysis (10.4% vs 5.9%), exacerbation of an underlying pulmonary disease (none vs 3.9%), and neuromuscular disorders (2% in each arm).
Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow
Disclosures
The study was funded by Insmed.
Daley reported relationships with Insmed, AN2 Therapeutics, Bugworks, Paratek Pharmaceuticals, Juvabis, AstraZeneca, Cepheid, Hyfe, MannKind, Matinas Biopharma, Nob Hill Therapeutics, Spero Therapeutics, Zambon, Genentech, Pfizer, Otsuka Pharmaceutical, Eli Lilly, and the Bill and Melinda Gates Foundation.
Taimur reported no disclosures.
Primary Source
American Thoracic Society
Source Reference: Daley CL "Change in patient reported respiratory symptoms in a randomized, double-blind, trial of amikacin liposome inhalation suspension in adults with newly diagnosed or recurrent Mycobacterium avium complex lung disease: the ARISE study" ATS 2024; Abstract A1032.
Secondary Source
American Thoracic Society
Source Reference: Daley CL "Microbiologic outcomes from a randomized, double-blind trial of amikacin liposome inhalation suspension in adults with newly diagnosed or recurrent Mycobacterium avium complex lung disease: the ARISE study" ATS 2024; Abstract A1033.
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MicuRx To Present New Data At 7th World Bronchiectasis Conference
SHANGHAI, June 19, 2024 /PRNewswire/ -- Shanghai MicuRx Pharmaceutical Co., Ltd. ("MicuRx", 688373.SH), a multi-asset biopharmaceutical company focused on the discovery and development of novel anti-infective therapies for treating life-threatening infections, today announced 3 new studies will be presented at the 7th World Bronchiectasis Conference, taking place from July 4 - 6, 2024 in Dundee, Scotland.
The presentations will showcase nonclinical data for MRX-5 and MRX-8. MRX-5 is an oral investigational candidate for the treatment of adults with nontuberculous mycobacteria (NTM) pulmonary diseases. MRX-5 demonstrates potent antimicrobial activity against Mycobacterium avium complex (MAC), the most common NTM pathogen, as well as Mycobacterium abscessus complex (MABC), the more difficult-to-treat NTM. MRX-5 is currently in Phase 1 clinical studies and topline results are expected in late 3Q2024.
MRX-8 is a novel compound in the polymyxin class. Nebulized MRX-8 is developed for treating chronic Pseudomonas aeruginosa lung infection in patients with bronchiectasis, including infections caused by drug resistant isolates.
Presentations pertaining to MRX-5 and MRX-8:
Title: In Vitro And In Vivo Activity Of A Novel Leucyl-Trna Synthetase Inhibitor Against Mycobacterium AbscessusPresenting Author: Regis Vilchez, MD, PhD (MicuRx)
Title: In Vitro Activity of Novel Leucyl-tRNA Synthetase Inhibitor Against Mycobacterium Avium ComplexPresenting Author: Wen Wang, PhD (MicuRx)
Title: In Vitro And In Vivo Activity Of A Novel Antibiotic In The Polymyxin Class Against Pseudomonas AeruginosaPresenting Author: Wen Wang, PhD (MicuRx)
About MicuRx
MicuRx is a biopharmaceutical company focusing on novel therapeutics for infectious diseases. With global independent intellectual property and competitiveness, we are committed to the discovery, development, and commercialization of innovative drugs for unmet medical needs. Since the company was founded in 2007, MicuRx has adhered to the principle of "Better therapy through superior medicine", focusing on the increasingly serious problem of global antimicrobial resistance.
For more information, please visit our website at www.Micurx.Com
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SOURCE MicuRx Pharmaceuticals
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