Review Paper

Is valganciclovir, or its intravenous equivalent, the best

preventive treatment for Cytomegalovirus?

Delaine M. Zayas-Bazán Burgos University of Puerto Rico

Abstract: Cytomegalovirus is a life altering and threatening infection that may cause serious complications in

risk patients. The patients who are in the risk population include immunocompromised patients and congenitally

infected infants. Immune system compromise may be caused by other conditions or by immuno suppressants.

Because of these complications, a series of studies have been conducted to discover the best treatment for the

infection. To date there are three known antivirals for cytomegalovirus. Of these, the best is valganciclovir.

Therefore, studies related to the use of valganciclovir were analyzed and compared. They confirmed that the

best treatment is valganciclovir, and, its intravenous equivalent, ganciclovir. Besides proving once more the

superiority of valganciclovir and ganciclovir, some external factors that contribute to their treatment success

were mentioned and discussed. These factors included the length of the study and the combination of

ganciclovir and valganciclovir in long-term regimens. Overall it was concluded that of the different antivirals

available for cytomegalovirus, valganciclovir was the most readily available, had less toxicity, and was highly

effective.

Introduction

Background

woff in 1959 stated that: “…all

true viruses have four

characteristics: They contain one

and only one type of nucleic acid; they are

reproduced from their genetic material and in the

form of their genetic material; they do not grow,

and they do not undergo binary fission; and they

posses no enzyme systems for energy production.”

With this definition, we can begin the discussion of

the main concept of this review paper:

cytomegalovirus. Cytomegalovirus is a virus from

the herpes virus family, which is composed of

viruses that contain DNA (Goodheart, 1969). The

herpes virus family is known by its latency and

reactivation mechanism. This mechanism consists

of a latency period occurring after contagion in

which the virus duplicates and infects other healthy

cells and the reactivation process, in which the virus

will express the disease and will damage the host

cells. This mechanism is also common among other

opportunistic infections similar to cytomegalovirus.

L

Because of this mechanism, the population

infected with cytomegalovirus can live without ever

knowing that they are infected. Currently more that

80% of the adult population of the world is infected

with cytomegalovirus that was recently classified as

an oncovirus. This classification means that it can

cause cancer or cancer related symptoms such as

tumors and abnormal cell growth.

Objectives

In this review paper, we discuss

valganciclovir and ganciclovir, its intravenous

equivalent, as the best treatment in the prevention of

cytomegalovirus. In the human body, valganciclovir

changes into ganciclovir, the intravenous

equivalent. It is proposed that the treatment of the

cytomegalovirus, with valganciclovir is the most

efficient and safest way of preventing

cytomegalovirus disease in immune compromised

patients thereby increasing their chances of

survival.

Development

Actual Treatments

Antiviral drugs also known as antivirotics

are currently the most common treatments dealing

with infections. Antiviral drugs do not destroy the

virus like antibiotics destroy bacteria. Instead, they

attack the virus by preventing the spread, slowing

the growth or by inhibiting its capacity to reproduce

and transmit its genetic material. Antivirotics are

not to be confused with vaccines. Vaccines are an

attenuated version of the virus that stimulates the

body to produce antibodies. These antibodies, once

infected, will block the capacity of duplication and

development of the disease in the individual.

Valganciclovir, and ganciclovir, is the best

known treatment for cytomegalovirus infection and

prevention. In Lombardi’s work in 2010 it is

registered that ganciclovir was the first medication

approved by the Food and Drug Administration and

that from 1990 it has been approved and used to

treat severe cytomegalovirus. Both of the

medications are currently being used to prevent and

treat cytomegalovirus disease in people who have

received different transplants or are risk patients.

Variables Compared and Contrasted

Many investigations are reviewed in this

paper in order to examine the success of

valganciclovir in the prophylaxis treatment of

cytomegalovirus infection. Different variables are

compared and contrasted. These are the length of

the study, dosage, sample, and effectiveness.

Length of the Study

The first difference between studies is the

duration of the treatment and the length of the

follow up. Of the three studies reviewed, the

lengths varied from 180 days up to 1,800 days.

These different variations showed a very important

aspect which is that the longer the treatment is

extended, in the case of solid organ transplants, the

better the outcome will be for the patient. The

follow up varied too, and it was important in

determining whether or not the treatment was

reliable. As it will be shown later, these two

variations made a difference in the results of the

diverse investigations compared.

Dosage: Amount and Entry Way

Two other variables differing in the studies

are the dosage of the medication and the way it

enters the body. In terms of the entry way, in one

study they utilized ganciclovir, which is

intravenous, in another study they also utilized

valganciclovir, which is oral, and in the last study

the medication was administered intravenously and

orally. In one of the studies the dosage was 450

milligrams tablets of oral valganciclovir, while in

the other two the dosage was of 900 milligrams

tablets. These variations in the dosages showed that

small portions of the medication are as effective as

large dosages. This also showed that in many cases

it is better to combine both entry ways: intravenous

and oral.

Sample: the patients

In some studies, the population was very

different to the population studied in other

investigations. For example, two of the studies can

be classified as solid organ transplant, while the last

one is about congenital cytomegalovirus. All of the

patients were immunocompromised and this

composed the main similarity among them.

The other aspect of the sample that merits

special attention is the size of the sample. This

differed from twenty-two to 157. Due to the

disparity in sample size, it was difficult to compare

results. For example, the results from the study with

twenty-two patients had one of the lowest success

rates because one out of eleven is a bigger fraction

than one out of eighty.

Effectiveness

In the studies that are being mentioned in this

review, the results were positive and confirmed previous

studies. The lowest success rate was in the study of

congenital symptomatic cytomegalovirus by Jacob Amir,

Dana G. Wolf and Itzhak Levy. This success rate was of

57% of improvement in patients, which is still a great

success. In Junichi Togashi, Yasuhiko Sugawara, Masao

Hashimoto, Sumihito Tamura, Junichi Kaneko, Taku

Aoki, Kiyoshi Hasegawa and Norihiro Kokudo’s

investigation the success rate was of 82% in the oral

valganciclovir group and of 91% in ganciclovir group.

Lastly, the success rate in the investigation by Scott M.

Palmer, Ajit P. Limaye, Missy Banks, Dianne Gallup,

Jeffrey Chapman, Clinton Lawrence, Jordan Dunitz,

Aaron Milstone, John Reynolds, Gordon L. Yung, Kevin

M. Chan, et all, was of 78% in the short-term group and

of 96% in the long-term group. In the following table

these success rates, along with other variables are

detailed.

Table 1. Comparison between studies: The aspect to be compared of the study is presented in the first column,

the author of the investigation in the second, third and fourth column. In the different rows the aspects are

detailed and contrasted.

Comparison and Analysis of the Table 1

These results are translated simply in the

confirmation of our prior aim. Valganciclovir, under

different circumstances is an effective treatment.

Different variables promote a better outcome, but

even if these variables are absent it is a great

treatment. Although not expressed before the

medication did not cause serious or unmanageable

secondary symptoms in any of the studies. These

results also show that different sectors of the risk

population are eligible to receive this treatment and

respond with great results.

Conclusions

In 2010 Caspar da Cunha-Bang and his team

stated in their investigation that: “… relatively few

studies have addressed combinations of risk factors

Variables to be compared

Investigation by Junichi Togashi et all

Investigation by Jacob Amir et all Investigation by Scott M. Palmer et all

Length of the study

The patients received the medication for 180 days. (approximately 6 months) The patients were followed 1 year after transplant, and three years after completion of the study.

The study was performed in 1,800 days (Approximately 60 weeks, 13 months or a year and one month) The infants were followed until they were three years old.

12 months of oral valganciclovir treatment The patients were followed for 6 months after the study’s completion.

Dosage

900 milligrams per day of oral valganciclovir or 5 milligrams per kilograms twice a day of intravenous ganciclovir

5 milligrams per kilogram of intravenous ganciclovir, every 12 hours for 6 weeks. Afterwards they were administered 450 milligrams tablets of oral valganciclovir, every 12 hours for t 6 weeks. Then one daily dose up to age 1 year. (The dose was adjusted to child’s growth after every kilogram of weight they gained)

intravenous ganciclovir for two weeks after surgery and then 900 milligrams of oral valganciclovir once a day

Sample

22 liver transplanted patients, 11 for each group.

23 infants born with cytomegalovirus.

157 lung transplant patients that had received the standard 3-months preemptive treatment.

Effectiveness

82% and 91% “In both groups, the overall 1-year survival rate after LDLT was 100%. The 1- and 3-year patient survival rates with CMV infection were 96% and 96%, versus 95% and 95% without CMV.”

The overall success was of 76% of improvement in the affected ears. In the other conditions caused by the virus the success was great. Many of the infants developed normally after 12 months of age.

68% of success (only 32% showed cytomegalovirus occurrence) and 96% of success (only 4% of cytomegalovirus occurrence)

predisposing to CMV infection.”. This statement is

one, of the many addressing the lack of

investigations concerning this disease. More

investigations and treatments in the prevention of

cytomegalovirus should be developed.

This review paper is the first, to our knowledge

that presents the main differences between the studies

that are being conducted about cytomegalovirus and

valganciclovir. In the review by Erin Wade Ticehurst,

Jennifer Trofe-Clark, Emily Blumberg and Roy D

Bloom, they discuss the effectiveness of valganciclovir

0in solid organ transplant recipients. They also show

several results that compare ganciclovir and

valganciclovir, but they do not determine which is the

best .

Based on this review, in congenital, lung

and other solid organ transplant, the best way to

prevent and treat cytomegalovirus is to combine

ganciclovir and valganciclovir in long treatment

regimens. Compared to the other two medications

approved in the treatment of cytomegalovirus

valganciclovir is superior. Two other medications

have been approved and are available. They are

foscarnet and cidofovir. Both of them remain as

second-line therapy for diverse reasons, among

those reasons is their high toxicity.

Valganciclovir as a preemptive treatment of

cytomegalovirus is effective, affordable and

accessible; therefore it is the best treatment

available. We can also conclude that a longer

treatment is better and raises the chances of not

acquiring the virus. These factors may change the

survival outcome of the patient.

Cytomegalovirus is a real threat, and it can

cause serious and life changing symptoms. There is

not enough information available for the public

about this virus and its possible effects in

inmunocompromised patients. More available

information will help patients, family members,

and communities struggling with the effects of this

virus.

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