A5355: Phase II, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA)-based Anti-Cytomegalovirus (CMV) Vaccine (Triplex®) in Adults with Both Human Immunodeficiency Virus (HIV)-1 and CMV Who Are on Potent Combination ART with Conserved Immune Function

HIV comorbidities and complications

Since the early days of the HIV epidemic cytomegalovirus (CMV) has been one of the most common and devastating opportunistic infections (OIs) experienced by people with HIV. CMV is a common virus that usually causes few, mild, or no symptoms and typically remains in the body for life; in people with weakened immune systems, however, CMV can cause more serious symptoms affecting the eyes, lungs, liver, esophagus, stomach, and intestines ). HIV and CMV can work together against our bodies’ defenses, making transmission of each virus easier. We would like to change this.

In this study, you will be randomized to one of the study treatment arms. You will receive either Triplex^® study vaccine or placebo by injection into the muscle of your shoulder 2 times; once when you enter the study and again about 4 weeks later.

The purpose of this study is to see if an investigational vaccine for CMV (called Triplex®) is safe when given to people with both HIV and CMV. This study will also collect information on the effectiveness of Triplex® to reduce inflammation and immune activation markers compared to a placebo. This will be the first time that this type of information will be collected. You should be aware that the current standard of care for individuals with both HIV and CMV includes effective treatment for HIV but does not include treatment of CMV with either medication or vaccination – unless there is evidence that the CMV is causing or contributing to illness.

Requirements to Enter Study (things that must be true for you):

• Living with HIV-1 and with cytomegalovirus (CMV).
• Be between 18 and 65 years old.
• On an anti-HIV medications that are controlling your HIV for at least the past year.
• Agree to use contraception/birth control methods if capable of becoming pregnant or impregnating someone else.

Exclusion Criteria (things that cannot be true about you):

• Use of anti-CMV drugs within the past 2 weeks.
• Currently have hepatitis B or hepatitis C
• Currently have a sexually transmitted infection (such as, gonorrhea, syphilis, or chlamydia)
• History of CMV disease and symptoms within the past 12 months.
• Receipt of any vaccine (including for COVID-19) within the previous 4 weeks.
• Recent serious illness or condition requiring hospitalization.
• Breastfeeding or pregnant.
• Historic or current evidence of resistance to the study medication or other medications in its class.

Talk to your study staff for a complete list of inclusion/exclusion criteria. 

Procedures:

• Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
• Questionnaires asking for information on adherence to ART and use of other drugs.
• For 4 weeks following each study injection you will complete a daily study diary (which is also known as a study vaccination report card); you will need to take and record your body temperature for the first 5 days each time.
• At several of the clinic visits, saliva, rectal swabs, and/or genital fluid (semen or vaginal swab) will be collected.

Intervention:

When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of two study groups. You will have double the chance of receiving Triplex^® versus the placebo. You must continue to take your anti-HIV drugs throughout the study.

About 2 years (96 weeks).