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VA research on

Infectious Diseases


Introduction

Infectious diseases can be caused by bacteria, viruses, fungi, or parasites. These microorganisms are commonly referred to as germs, and they can be present on a person's skin or inside their body. While most microorganisms are harmless, some can cause disease under certain conditions.

Some infectious diseases are passed through the air by coughing or sneezing. Other diseases are transmitted through insect or animal bites, ingesting contaminated food or water, or being exposed to pathogens in the environment.

VA has determined that nine infectious diseases are related to military service in the first Gulf War, Iraq, and Afghanistan. They include malaria, brucellosis, campylobacter jejuni, coxiella burnetii (Q fever), mycobacterium tuberculosis, nontyphoid salmonella, shigella, visceral leishmaniasis, and West Nile virus. A fuller description of these diseases can be found here.

Certain infectious diseases can be treated with antibiotics, for instance, those caused by bacteria and fungi. However, many germs have become resistant to antibiotics. Bacteria, for example, can mutate so that they are no longer susceptible to antibiotics. When that happens, it is more difficult to treat those infections and patients often require extended hospital stays. Antibiotic resistance has become a public health threat.

A new type of coronavirus, SARS-CoV-2, emerged around the world in 2019 and became widespread in 2020. The disease it causes, COVID-19, can produce mild-to-severe respiratory illness and even death.  Its symptoms can include fever, chills, cough, shortness of breath, fatigue, and body aches. People who contract the disease may also experience loss of taste or smell, as well as multiple other physical and cognitive effects. VA has implemented a strong public health response to protect and care for Veterans, their families, health care providers, and staff in the face of this urgent health risk.

Among the steps VA is taking to prevent COVID-19 transmission are outreach to Veterans and staff, clinical screening at VA health care facilities, vaccinations, and protective procedures for patients admitted to community living centers and spinal cord injury units.

To find out about VA research on the new coronavirus, visit the COVID-19 topic page to learn about clinical trials, data analyses, and research partnerships that are taking place to find ways to prevent and treat COVID-19.

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Selected Major Accomplishments

  • 1946: Developed and tested effective therapies for tuberculosis through multicenter clinical trials that led to the development of the VA Cooperative Studies Program
  • 2005: Demonstrated the effectiveness of a new vaccine for shingles, a painful skin and nerve infection affecting older adults
  • 2011: Published findings showing a 60% or greater decrease in methicillin-resistant Staphylococcus aureus (MRSA) infections from a VA-wide infection control initiative
  • 2014: Learned that treatment for pneumonia that included the antibiotic azithromycin (Zithromax) was associated with a significantly lower risk of death and a slightly increased risk of heart attack
  • 2015: Found that patients who received antiretroviral therapy within a year of their infection were half as likely to develop AIDS, compared with those who waited longer
  • 2016: Determined that a hospital infection-control program aimed mainly at MRSA can also significantly reduce transmission of bacteria that cause infections such as pneumonia, blood infections, surgical infections, and meningitis
  • 2018: Found that people on a single tablet regimen for HIV infection had better outcomes than those on a multi-pill regimen to suppress the virus
  • 2018: Partnered with the Centers for Disease Control and Prevention to ramp up the fight against infectious diseases
  • 2021: Learned that patients who recover from COVID-19 are at risk for persistent, long-lasting health problems

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New, Ongoing, and Published Research

VA researchers are advancing the understanding, prevention, and treatment of numerous infectious diseases, ranging from the common cold to major public health threats such as COVID-19, tuberculosis, AIDS, hepatitis C, and influenza. They have developed a number of effective new prevention strategies, vaccines, and drugs to treat infectious diseases.

Some researchers are focusing on infectious diseases that may endanger American troops serving abroad, such as malaria and leishmaniasis. Others are searching for new approaches to treat infectious diseases, focusing on how pathogens change, and drug resistance evolves.

VA’s Health Services Research and Development Service is partnering with the Centers for Disease Control and Prevention (CDC) to create a research network that will identify ways to better protect patients and employees from infectious diseases in VA medical centers. Researchers will carry out studies in infection control and the proper use of antimicrobial drugs to best meet the growing threat of multi-drug resistant pathogens.

For more information on infectious diseases, visit our Hepatitis, Respiratory Health, and COVID-19 topic pages.

If you are interested in learning about joining a VA-sponsored clinical trial, visit our research study information page.

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➤ Historical studies

One of the earliest contributions made by VA researchers was establishing effective treatments for tuberculosis (TB), a bacterial disease that is spread through the air from one person to another. TB can be fatal if not treated properly.

Evidence of tubercular decay has been found in the spines of Egyptian mummies thousands of years old, and TB was common in ancient Greece and Imperial Rome. As late as the 19th century, the disease occurred at epidemic proportions in Europe and North America, and TB remained a major health problem well into the 20th century.

The first head of VA research was a TB specialist, and in the 1920s and 1930s, VA researchers published a number of scientific papers on the subject. After World War II, VA and the Department of Defense conducted a major study to test the effectiveness of the antibiotic streptomycin to treat TB. While initial results were very favorable, researchers soon learned that the antibiotic could cause inner ear damage and that many patients developed resistance to the drug.

In 1947, however, VA researchers determined in a follow-up study that a lower dose of streptomycin could achieve similar good results with fewer side effects and less risk of drug resistance. These studies, conducted at a number of VA facilities, were among VA's first-ever large-scale clinical trials. They eventually led to the development of VA's Cooperative Studies Program in 1972, which plans and conducts large, multicenter clinical trials and epidemiological studies for VA.

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➤Tuberculosis

TB rates in the United States have fallen to all-time lows, largely thanks to antibiotics such as streptomycin and its successors. In 2019, there were 8,916 cases of TB in the United States. As many as 13 million Americans have a latent case of TB, according to the CDC. Latent TB is when a person has the TB bacteria but does not display symptoms and is not infectious to others.

Four months of multi-drug therapy that included rifapentine and moxifloxacin treated active TB as effectively as the standard six-month regimen, according to an international study published in 2021 that included researchers from the VA San Antonio Health Care System.

Drugs to treat TB have been around for more than 20 years and are widely available. However, a shorter course of treatment would be easier for people to complete without missing doses, and may ultimately be more cost effective. The study enrolled more than 2,500 people in 13 countries, including nearly 200 people living with HIV, the virus that causes AIDS. Patients with HIV and a latent TB infection are at greater risk of progressing to active TB disease.

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➤Shingles

Shingles, or herpes zoster, results from the reactivation, multiplication, and spread of chickenpox virus that remains dormant in sensory nerves. It is marked by a painful, blistering rash, and can affect anyone who had chickenpox as a youth. Doctors in the United States treat more than a million cases of shingles each year.

Most cases of shingles clear up within two to three weeks, but some patients suffer anguishing nerve pain for months or even years. This stage, called postherpetic neuralgia, can involve burning, throbbing, stabbing, or shooting pain and can lead to insomnia, weight loss, depression, and other medical problems.

Shingles vaccine trial—In 2005, VA researchers and their colleagues published the results of the Shingles Prevention Study, one of the largest adult vaccine trials anywhere. The results showed that a live, attenuated zoster vaccine was well tolerated and protected older adults over 60 from shingles and postherpetic neuralgia.

Since then, the study team has continued to study the vaccine's benefits and ways it can be used most efficiently.

Zoster vaccine safe in older population—Researchers throughout VA in a 2013 study found the vaccine to be safe for older adults with a prior history of shingles. They have also determined the vaccine is safe and effective for people in their 50s (the original trial included only people 60 and older) and that the efficacy of the vaccine gradually declines in the years following vaccination, so a second dose may be needed.

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➤HIV/AIDS

Human immunodeficiency virus (HIV) is a chronic, progressive disease that leads to acquired immune deficiency syndrome (AIDS). The virus was first identified 30 years ago. According to amfAR, the Foundation for AIDS Research, 38 million people worldwide are now living with HIV infection. In the United States, VA is the single largest provider of medical care for HIV/AIDS.

VA researchers are focused on improving HIV identification and screening rates in primary care settings, managing complex challenges for Veterans with HIV, and improving access to care for Veterans at risk of HIV due to geographic, racial, or ethnic status. Screening for HIV is crucial because up to a quarter of people with HIV don't know they have it.

Abnormal lung function with HIV—A 2020 study by researchers at the Minneapolis VA Health Care System, the University of Minnesota, and other institutions found there is a greater risk for impaired lung function among men with HIV than those without.

The team tested 591 HIV-positive and 476 HIV-negative men for lung function. They found men with HIV were more likely to have abnormal lung function, based on low diffusing capacity in their lungs. Diffusing capacity measures the ability of the lungs to transfer oxygen into red blood cells, which carry it to other parts of the body.

Low diffusing capacity has been linked to worse quality of life, worse exercise capacity, and a higher risk of respiratory disease. The team suggested the most important thing HIV-positive men can do to avoid this issue is to eliminate exposure to cigarette smoke, including second-hand smoke.

HIV drug may increase kidney disease and fractures—A common treatment for HIV is associated with higher odds of chronic kidney disease and bone fractures, according to a 2020 study by researchers at the W.J.B. Dorn VA Medical Center in Columbia, South Carolina, and the University of South Carolina.

Among 5,000 VA patients with HIV, those taking the drug tenofovir disoproxil fumarate (sold as Viread) were 48% more likely to develop chronic kidney disease compared with those who did not. They also had more than twice the risk of bone fracture due to bone deterioration or low bone mass.

HIV regimens using this drug have been associated with impaired kidney function and loss of bone mineral density in the past, and the results of this study shed a light on the extent of this association.

Single-tablet HIV regimen shows advantage—HIV patients on a single-tablet daily regimen had better viral suppression than patients taking multiple pills, according to a 2018 study by researchers at the Michael E. DeBakey VA Medical Center in Houston and their colleagues.

Early antiviral therapy for HIV involved taking up to a dozen pills each day. Today, once-daily regimens are the new standard of care for the condition, but vary in the number of pills taken. Researchers compared two groups of HIV patients who were taking a single pill daily versus multiple pills daily. They found that taking a single tablet once a day increases patients’ quality of life and improves the likelihood they will adhere to their treatment.

After following the patients for a year, the team found that HIV patients who took one daily pill versus multiple pills better suppressed the virus in their blood. The team was unclear about why the single-tablet regimen led to better clinical outcomes.

For people who do not treat their HIV infection, the average survival time is 9 to 11 years.

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➤Influenza (flu)

Influenza (the flu) is a contagious respiratory illness that infects the nose, throat, and lungs. The flu viruses can produce mild to severe illness, and sometimes cause death. The best way to prevent the flu is by getting a flu vaccine each year.

Disadvantaged patients less likely to get flu shots—Socioeconomic factors can predict the likelihood of flu vaccination in patients with diabetes, according to a 2020 study that included a researcher at the Michael E. DeBakey VA Medical Center in Houston. 

The study looked at data on more than 25,000 patients with diabetes. About 36% of those patients did not receive a flu shot. Younger age, Black race/ethnicity, being uninsured, and having no usual source of health care all decreased the odds of getting a flu shot. Nearly 64% of patients with all four of these socioeconomic factors did not receive a flu shot. 

According to the research team, the findings highlight the need to increase vaccine coverage in disadvantaged communities.

COVID-19 patients at greater risk of death, health problems—Among hospitalized patients, COVID-19 was associated with an increased need for ventilators, more admissions into intensive care units (ICUs), longer hospital stays, and nearly five times the risk of death than patients with the flu.

In a study published in 2020, researchers at the St. Louis VA Health Care System and the Washington University School of Medicine examined data from 3,641 Veterans hospitalized with COVID-19 during the period Feb. 1 to June 17, 2020. They also looked at data from 12,676 patients hospitalized with the flu during the period January 2017 through December 2019.

Patients infected with COVID-19 were nearly five times more likely to die than those with influenza, four times more likely to require breathing machines, and almost 2.5 times more likely to be treated in the ICU. Also, COVID-19 patients were more likely to be hospitalized an average of three days longer than flu patients.

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➤Pneumonia

Pneumonia is an infection caused by viruses, bacteria, or fungi that inflame the air sacs in one or both lungs. It is a common infection and is most serious in infants, people who are immunocompromised, and those who are over 65 years old. Each year, close to 1 million adults in the United States seek hospital care for pneumonia, and 50,000 adults die from the disease.

Broad-spectrum antibiotics ineffective for pneumonia—Patients who are given drugs that target antibiotic-resistant bacteria as a first-line defense against pneumonia fare no better than those who receive standard medical care.

A 2020 study by researchers at the VA Salt Lake City Health Care System and the University of Utah looked at records for 88,000 Veterans hospitalized with pneumonia between 2008 and 2013. They wanted to know whether Veterans were initially treated with standard antibiotic therapy, standard therapy plus an antibiotic called vancomycin, or vancomycin without standard therapy. Vancomycin is a drug that can help prevent the development of methicillin-resistant staphylococcus aureus (MRSA) in the lungs, which can cause a rare but hard-to-treat form of pneumonia.

The team found no discernable benefit from using vancomycin in addition to standard treatment. The study is one of the largest ever to examine trends of antibiotic use in the treatment of pneumonia. 

Tooth brushing prevents pneumonia—Adequate oral care keeps harmful bacteria from migrating into patients’ lungs and causing pneumonia, according to a 2019 study led by researchers at the Salem VA Medical Center in Virginia. Removing the biofilm that accumulates around teeth by brushing twice a day reduced the number of monthly cases of pneumonia at Salem’s VA Community Living Center (CLC) from four to zero.

Salem’s work in reducing pneumonia by providing CLC patients with effective and consistent delivery of oral care has been replicated in eight other VA medical centers, and the VA health system is in the process of adopting the innovation nationwide.

Tocilizumab (TCZ) may treat severe pneumonia—TCZ, a drug often used to treat rheumatoid arthritis, is the focus of an ongoing clinical trial for COVID-19 patients with severe pneumonia. VA medical centers in Houston and Miami are among nearly 70 medical sites worldwide participating in the international study of the drug.

TCZ is in a class of drugs that reduce the strength of the body’s immune system. It is often used to treat rheumatoid arthritis, a chronic condition characterized by joint inflammation. It has the potential to block interleukin-6, a chemical that plays a key role in the body’s immune response and is involved in the development of many diseases.

All enrolled study participants must be newly hospitalized from pneumonia. They will be monitored for 28 days for their response to treatment, which includes disease progression, length of hospitalization, and the need for critical care. The primary study outcome is the number of participants who require mechanical ventilation by day 28. A secondary study outcome is the number of patients who die.

The researchers hope TCZ can prevent the inflammatory response in COVID-19 pneumonia that leads to uncontrolled inflammation and respiratory failure.

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➤Hospital-acquired infections

Methicillin-resistant Staphylococcus aureus (MRSA) is a type of staph bacteria that is resistant to certain antibiotics called beta-lactams. These antibiotics include methicillin and other antibiotics such as oxacillin, penicillin, and amoxicillin.

MRSA is a dangerous organism that can cause pneumonia or other infections. It is primarily spread through direct physical contact with an infected person or object, and typically resides on the skin or in the nose. MRSA is associated with invasive health care procedures or devices, like surgery or IV tubing, and is difficult to eradicate.

To combat MRSA, VA obtains nose swabs from all patients when they are admitted, transferred, or discharged; isolates all patients who test positive for MRSA; emphasizes the importance of thorough hand-washing for all staff; and is working to continuously improve infection control at all VA facilities.

Infection control at community living centers—Asking environmental service workers for their perspectives on infection control at VA community living centers (CLCs) is an important aspect of improving infection control policies, according to a 2020 paper by researchers at the Iowa City VA Medical Center and the VA Maryland Health Care System in Baltimore.

The research team interviewed 40 staff members at five VA CLCs to assess their knowledge, attitudes, and beliefs concerning infection prevention and resident-centered care. They found those interviewed felt challenged by the need to maintain effective infection control while still providing a home-like environment for residents. They also found environmental service workers had a unique way of thinking about infection control that typically was not considered by others at their facilities. These workers thought globally about controlling infection throughout the many different spaces and domains every CLC has.

The team interviewed epidemiologists, infectious disease specialists; nurse managers; nursing assistants; and environmental service workers, sometimes referred to as housekeeping staff. The investigators believe infection-control team members will find environmental service workers to be “natural, untapped allies” in improving policies at VA CLCs.

Inadequate hand hygiene in hospitals—Frequent switching of reminder signs does not improve compliance with hand hygiene in hospitals, according to a 2019 study at nine VA medical centers. Studies have shown that health care workers who use proper hand hygiene when they are in direct contact with patients can reduce hospital-acquired infections. However, adherence to hand-washing guidelines in hospitals is low.

The researchers aimed to boost adherence to hand-hygiene guidelines by changing visual reminders inside and outside patient rooms more frequently. Signs next to antibacterial hand soap dispensers were changed either weekly or monthly to make them more noticeable. A third group were left the same. Over six months, hand-washing rates remained the same in all three groups overall, and actually declined in the group that had the most-frequent sign changes.

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➤C. difficile

Clostridium difficileC. difficile or C. diff—is a bacterial infection in the colon that is difficult to treat. It typically occurs in older patients in hospitals or long-term care facilities after the use of antibiotics. The organism can cause mild to severe disease and has a very high recurrence rate. As many as 30% of patients experience recurrent episodes of C. difficle after an initial infection.

More study needed on C. difficile prevention—A 2020 study of C. difficile in VA facilities did not find a clear link between prevention practices and infection rates. Researchers from five VA medical centers surveyed C. difficile rates at 123 VA facilities.

Since VA implemented new prevention practices in 2012, the team found that 49% of health care facilities reported decreased C. difficile rates, 18% reported an increase, and 33% reported no change. The variation did not appear to be linked to self-reported cleaning practices, length of contact precautions, use of private rooms, or certification of infection preventionists.

According to the researchers, more study is needed on which practices best prevent C. difficile spread.

Toilet flushing increases bacterial contamination—Researchers at the Iowa City VA Medical Center found that flushing the toilet may contribute to the spread of harmful bacteria in hospitals.

In a 2020 study, researchers took air samples in the rooms of patients with C. difficile infections and found that the concentration of harmful bacteria were significantly higher after the toilet was flushed. Flushing a toilet can send tiny particles of fecal matter into the air. The researchers suggest that hospitals evaluate their prevention measures and add toilet lids where they are not currently in place.

More on Our Website

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Selected Scientific Articles by Our Researchers

Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. Dorman SE et al. The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718.

Alcohol use and antiretroviral adherence among patients living with HIV: is change in alcohol use associated with change in adherence? Williams EC et. al. Increased alcohol use leads to a decrease in medication adherence in patients with HIV, as does a decline in alcohol use. Those whose alcohol use remained steady had the most stable medication adherence. AIDS Behav. 2021 Jan;25(1):203-214.

Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with covid-19 and seasonal influenza: cohort study. Xie Yan, Bowe B, Maddukuri G, Al-Aly Z. COVID-19 is associated with an increased need for ventilators, more admissions into intensive care units (ICUs), longer hospital stays, and nearly five times the risk of death than faced by those with the flu. BMJ. 2020 Dec 15;371:m4677.

Association of tenofovir disoproxil fumarate exposure with chronic kidney disease and osteoporotic fracture in US veterans with HIV. Sutton SS, Magagnoli J, Hardin JW, Hsu LI, Beaubrun A, Majethia S, Cummings TH. In a large cohort of U.S. Veterans with HIV, current exposure to tenofovir disoproxil fumarate was associated with a 48% higher odds of chronic kidney disease and a greater than two-fold increase in the odds of osteoporotic fracture. Curr Med Res Opin. 2020 Oct;36(10):1635-1642.

Prevalence of and sociodemographic disparities in influenza vaccination among adults with diabetes in the United States. Bhugra P, Mszar R, Valero-Elizondo J, Grandhi GR, Virani SS, Cainzos-Achirica M, Vahidi FS, Omer S, Nassir K. One-third of adults with diabetes in the United States lack influenza vaccination, with younger age, Black race, and lower socioeconomic status serving as strong predictors. J Endocr Soc. 2020 Sep 24;4(11):bvaa139.

Lung function in men with and without HIV. Kunisaki KM, Nouraie M, Jensen RL, Chang D, D’Souza G, Fitzpatrick ME, McCormack MC, Stosor V, Morris A. HIV-positive men are at increased risk of abnormal gas exchange, indicated by low diffusing capacity for carbon monoxide, compared with men without HIV. AIDS. 2020 Jul 1;34(8):1227-1235.

Bioaerosols generated from toilet flushing in rooms of patients with Clostridioides difficile infection. Wilson GM, Jackson VB, Boyken LD, Schweizer ML, Diekema DJ, Petersen CA, Breheny PJ, Nonnenman MW, Perencevich EN; CDC Prevention Epicenter Program. Bioaerosols produced by toilet flushing potentially contribute to hospital environmental contamination. Infect Control Hosp Epidemiol. 2020 May;41(5):517-521.

Empirical anti-MRSA vs. standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia. Jones BE, Ying J, Stevens V, Haroldsen C, He T, Nevers M, Christensen MA, Nelson RE, Stoddard GJ, Sauer BC, Yarbrough PM, Jones MM, Goetz MB, Greene T, Samore MH. Empirical anti-MRSA therapy is not associated with reduced mortality for any group of patients hospitalized for pneumonia. JAMA Intern Med. 2020 Apr 1;180(4):552-560.

Environmental service workers as potential designers of infection control policy in long-term care settings. Van Tiem JM, Friberg JE, Goedken CC, Pineles L, Resinger HS, Morgan DJ, Solimeo SL. Environmental service workers' daily work inside patientrooms and within the wider facility produces a unique perspective that might help in the design of workable infection control policies in CLCs. Am J Infect Control. 2020 Apr;48(4):398-402.

Correlation of prevention practices with rates of health care-associated Clostridioides difficile infection. Musuuza JS et al. The research team found considerable variation in C. difficile infection rates among VA facilities, but was unable to identify which particular practices were associated with lower rates. Infect Control Hosp Epidemiol. 2020 Jan;41(1):52-58.

Effect of frequency of changing point-of-use reminder signs on health care worker hand hygiene adherence: a cluster randomized clinical trial. Vander Weg MW et al. The frequency of changing reminder signs had no effect on hand hygiene rates overall. JM Netw Open. 2019 Oct 2;2(10):e1913823.

National trends in the treatment of urinary tract infections among Veterans Affairs Community Living Center residents. Appaneal, HJ, Caffrey AR, Lopes VV, Crnich CJ, Dosa DM, LaPlante KL. Over a 5-year period, antibiotic use for UTIs significantly decreased among VA CLCs, as did use of fluoroquinolones. Infect Control Hosp Epidemiol. 2019 Oct;40(10):1087-1093. 

Implementation and dissemination of a Department of Veterans Affairs oral care initiative to prevent hospital-acquired pneumonia among nonventilated patients. Munro S, Haile-Mariam A, Greenwell C, Demirci S, Farooqi O, Vasudeva S. Implementation and dissemination of an oral care initiative enhanced the safety and well-being of Veterans at the Salem VA Medical Center by reducing the risk of non-ventilator-associated hospital-acquired pneumonia. Nurs Adm Q. 2018 Oct/Dec;42(4):363-372.

Single tablet HIV regimens facilitate virologic suppression and retention in care among treatment naïve patients. Hemmige V, Flash CA, Jarter J, Giordano T, Zerai T. Retention in care and virologic outcomes were better in patients prescribed a single-tablet daily regimen for HIV. AIDS Care. 2018 Aug;30(8):1017-1024.

Gaps up to 9 months between HIV primary care visits do not worsen viral load. Garner LI, Marks G, Patel U, Cachay E, Wilson TE, Stirratt M, Rodriguez A, Sullivan M, Keruly JC, Giordano TP. HIV primary care visit intervals of six to nine months for select patients may be appropriate. AIDS Patient Care STDS. 2018 Apr;32(4):157-164.

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