Wednesday, October 24, 2018

ART Chronicles: CD4 Count and Viral Load


By: Ronald Bugarin







Every newly diagnosed Person Living with HIV (PLHIV) has to absorb a wealth of information about their journey towards and in treatment.  Among the multitude of terms to remember, most commonly used are “CD4 Count” and “Viral Load” but what do these terms really mean and how important are they to every PLHIV who are on Antiretroviral Therapy (ART)?


CD4 Count

CD4 cells (also known as T-cells, or T helper cells) are white blood cells that fight off infections that enter the body.  Its main function is to send signals upon entry of a virus or bacteria to other types of immune cells, including CD8 cells to fight off the cells infected by bacteria and viruses.


Upon successful HIV transmission in the body, the virus enters the CD4 cells and replicates after which, new copies of the virus will then be released and attaches to other CD4 cells. This ultimately opens the body to possible opportunistic infections due to the continuous decline of the CD4 and CD8 cells.

CD4 count is tested upon HIV diagnosis to check the current state of the immune system. Likewise, CD4 Count serves as indicators of possible risk of opportunistic infections and advanced HIV infection.  It remains as a vital test that can help HealthCare Providers (HCPs) in their decisions for empiric treatment, particularly for PLHIV with advanced HIV infection.

Below is a table showing the normal range of CD4 Count as well as PLHIV CD4 Count in cubic millimeter (mm3):

CD4  COUNT
IMMUNE SYSTEM STATUS
Between 500 to 1,500 cells/mm3
Normal CD4 range, immune system is healthy
Below 500 cells/mm3
Possibly immune compromised if PLHIV
Below 350 cells/mm3
Advanced immune compromised if PLHIV, with possible opportunistic infections

Since 2013, the World Health Organization (WHO) guidelines in administering ART to PLHIV has set the threshold to below 500 cells/mm3  for the start of ART, giving priority to those with advanced HIV infection or with a CD4 Count of below 350 cells/mm3.  But in 2015, two large randomized controlled trials on the efficacy of ART at varying CD4 Count levels showed that starting ART, regardless of CD4 Count, has showed significant decline in the progression of the infection. Thus, WHO updated their guidelines in September 2015 to strongly recommend that all PLHIV should start with ART regardless of their CD4 Count and stop monitoring the CD4 Count of PLHIV who are already stable in their ART.

CD4 Count are measured prior to start of ART.  Upon ART initiation, CD4 count monitoring could be done every 3 to 6 months or upon ART failure.

Viral Load

Viral load (VL) is the amount of HIV present in your blood. The higher the viral load, the quicker a person’s immune system will be damaged, increasing their risk of opportunistic infections. Also, viral load provides an early and more accurate indication of ART failure and the need for a change in ART combination, which also reduces the risk of drug resistance (HIV becoming resistant to the ART’s efficacy) among PLHIV.

Viral load of PLHIV should be monitored routinely at 6 and 12 months interval from initial HIV diagnosis and then every 12 months thereafter to ensure the stability of the ART and detect treatment failure earlier and more accurately.  Monitoring PLHIV who are linked to care is important to ensure successful treatment, to identify adherence problems and to determine whether ART regimens should be changed.


ART failure occurs when the viral load of a PLHIV exceeds 1000 copies/mL based on two consecutive viral load measurements within a 3-month interval.  Adherence support and counselling are needed following the first viral load test to prevent drug resistance.

An Undetectable viral load (less than 34 copies/mL) is the ultimate indication of ART’s effectiveness and is a goal that many PLHIV strive for. This is also crucial with the recent pronouncement of UNAIDS that PLHIV who adhere to their ART and have undetectable status can no longer transmit HIV. This means that ART adherence can be a way to stop the spread of HIV.


CD4 Count versus Viral Load

Upon start of treatment, ART suppresses the further replication of CD4 cells infected with HIV. Upon viral suppression, the immune system then has a chance to recover naturally and ultimately fight off any opportunistic infections attacking the body.

The graph below shows the correlation of CD4 cells and viral load before and after ART initiation.  If a PLHIV does not start with ART upon diagnosis, the CD4 count decreases while the viral load continues to increase.  Likewise, when ART has been initiated, CD4 count slowly increases while the viral load decreases. Hence, CD4 count has an inverse correlation with viral load.

Image Retreived from: https://commons.wikimedia.org/wiki/File:Hiv-timecourse_copy.svg
Recent studies suggest that in situations where viral load testing is routinely available and individuals are virally suppressed (Undetectable), long-term CD4 Count monitoring adds little value and stopping CD4 Count for monitoring purposes will have major cost savings.

Below are the various CD4 Count and Viral Load Testing cost in selected hospitals / treatment centers:

Laboratory Clinic / Hospital
CD4
Viral Load
The Medical City I-REACT (Individual Rate)
1,715.00
13,900.00
The Medical City I-REACT (Group Rate)

6,230.00
Makati Medical Center
5,135.00
8,835.00
St Luke’s Medical Center (Global City)
2,575.20
8,689.60
St Luke’s Medical Center (Quezon City)
6,885.00
10,655.00
LoveYourSelf Anglo***
1,500.00
7,500.00
San Lazaro Hospital
2,000.00
5,000.00
National Kidney Transplant Institute
4,600.00
4,900.00
*** Please take note that LoveYourself offers its Viral Load and CD4 tests to clients enrolled in our treatment program for FREE. The prices in the table are cost assumptions for those services should if costed.


CD4 Count and Viral Load testing are covered by the Outpatient HIV/AIDS Treatment (OHAT) Package of Philhealth per Philhealth Circular No. 011-2015.  Per Department of Health Administrative Order No. 2014-0031, CD4 cell count is done to alert physicians if the ART regimen has no effect in immune recovery or potential adherence issues. Declining CD4 count can be used as basis for switching ART combination but the measurement has to be repeated which can be financially straining on PLHIVs.  Also, where viral load monitoring is not available, clinical monitoring and CD4 monitoring are then recommended. A number of countries have either reduced the frequency of or stopped routine CD4 Count monitoring for PLHIV who are stable on ART and rely on viral load alone to monitor the response to ART and detect potential viral failure. As shown in the cost comparison table above, it is quite expensive to have regular CD4 Count monitoring on top of the viral load testing since the OHAT Package of Philhealth only covers the initial CD4 Count testing.


Whether CD4 Count or viral load is used as basis in monitoring ART effectiveness, it is also crucial to have a comprehensive and achievable adherence counselling for our PLHIV to empower them on their journey towards a stable immune status and long term HIV viral suppression.

For more information on HIV Treatment as well Life Coaching Services, you may visit LoveYourself Anglo and Victoria by LoveYourself


References:
  1. Undetectable = Untransmittable Public Health and HIV Viral Load Suppression
  2. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection Recommendations for a Public Health Approach (Second Edition 2016)
  3. The Evolving Role of CD4 cell counts in HIV Care

Illustrations by TJ Gellada Monzon
Storyboard by Franco Moje and Mark de Castro
(Inspired by the Japanese manga series “Cells At Work”)

Monday, October 08, 2018

HIVisions: Hearing and HIV

By Carlos Diego A. Rozul

From the booming sounds during a party to the gentle whispers from a significant other, the sense of hearing plays a significant role in making our days more vibrant. For hearing people, it is an essential to understand and appropriately respond to verbal communication. In recent years, researchers[1] in the field of HIV care has put their attention towards the hearing health of people living with HIV (PLHIV). A 2013 integrative review by Assuiti, Lanzoni, dos Santos, Erdmann, and Meirelles[2] revealed that there was not enough evidence for a direct association or implication of antiretroviral therapy (ART) and hearing loss, however they suggested to investigate the associated factors further due to inconclusive data.

Image retreived from https://www.flickr.com/photos/photobythomas/11535403595/in/album-72157644872472185/
Hearing Complaints among PLHIV

According to van der Westhuizen, Swanepoel, Heinze, and  Hofmeyr[3] PLHIV were more likely to report auditory and otological symptoms such as tinnitus, vertigo, and otalgia due to otitis media while a few others have reported sensorineural hearing loss, especially for those who are in the advanced stages of the infection. It was previously suggested[4] that this was due to the direct action of the virus on the central auditory system, however there is also evidence pointing towards it acting upon the peripheral auditory pathway as well[5], which occurs more often when viral load is high.

Two major concerns for people living with HIV who are not enrolled in treatment are co-occurring infections that one may have when first infected, and opportunistic infections. When it comes to risk for hearing loss, CMV infection[6], bacterial meningitis[7], otosyphilis[8] are of the most concerning. Due to non-treatment, PLHIV may become immunocompromised wherein their immune system becomes less effective defending against pathogens. As such, those related to the neural and auditory system may significantly affect one’s hearing. With adherence to treatment however, these concerns are eliminated.

Image retrieved from: https://pixabay.com/en/pregnancy-woman-asian-2594275/
The Case with Pregnant Women Living with HIV

Aside from the mother, there is additional concern for the child a woman carries when she is infected with HIV. Maternal health and health behaviors can influence the development of the child, as such they are even more vulnerable for prenatal TORCH infections - one of the most common causes of congenital hearing loss. Among these are toxoplasmosis which has 70% incidence rate of hearing loss[9], rubella which is declining due to immunization programs[10], CMV wherein 33-50% of hearing loss incidences have late onset[11], and HSV which is transmitted when the child is delivered vaginally[12].

Image retrieved from https://www.flickr.com/photos/niaid/32483530942
Antiretroviral Medication and Hearing

Past studies[13] have shown a trend of higher hearing thresholds among PLHIV on treatment as compared to non-infected individuals, however inconclusive with regards to the mechanism of action[2]. Findings are mixed with some suggesting that components of some ART combinations such as nucleoside analog reverse transcriptase inhibitors[14], Epzicom, and Trizivir[15] have the potential to adversely affect hearing; while others suggest that HIV infection and ART adherence have no impact on cochlear function.

Image retrieved from https://www.facebook.com/PHnewbornhearingscreening/
In some ways, living with HIV and hearing loss are quite similar. Both are silent conditions that can only be identified when one decides to get tested. However, they do not need to coincide. Treatment is readily available for PLHIV in the Philippines to prevent any opportunistic infections that can cause hearing loss. The Universal Newborn Hearing Screening and Intervention Act of 2009 also ensures that all newborns, regardless of risk, are screened for hearing loss.

So talk to your doctor if you have any concerns with your own or your child’s hearing.  You can be referred to a Certified Newborn Hearing Screening Center or Hearing Center near you.

References
  1. https://www.audiology.org/news/hiv-and-hearing-loss
  2. http://www.scielo.br/pdf/bjorl/v79n2/en_v79n2a19.pdf
  3. http://yvdwaudiology.co.za/wp-content/uploads/2017/05/2013_Westhuizen-Swanepoel_IJA.pdf
  4. https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/1471-2334-6-28
  5. http://www.producao.usp.br/bitstream/handle/BDPI/9160/art_MATAS_Avaliacao_auditiva_na_Sindrome_da_Imunodeficiencia_Adquirida_2010.pdf?sequence=1
  6. https://www.sciencedirect.com/science/article/abs/pii/S0753332297823268
  7. https://www.researchgate.net/profile/Elizabeth_Molyneux/publication/8963254_The_effect_of_HIV_infection_on_paediatric_bacterial_meningitis_in_Blantyre_Malawi/links/02bfe50f78a79cb76f000000/The-effect-of-HIV-infection-on-paediatric-bacterial-meningitis-in-Blantyre-Malawi.pdf?origin=publication_detail
  8. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1468-3083.2004.00939.x
  9. https://www.ncbi.nlm.nih.gov/pubmed/8770668
  10. http://www.bioline.org.br/request?hg06026
  11. https://www.jpeds.com/article/S0022-3476(99)70328-8/ppt
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/
  13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081880/pdf/cln-69-07-469.pdf
  14. https://academic.oup.com/cid/article/32/11/1623/464432
  15. https://www.ncbi.nlm.nih.gov/pubmed/24487230
_______________________________________________________
Carlos Diego is an HIV counselor and the Head of Editorial for LoveYourself. Outside of volunteering, he is a clinical audiology student and a registered psychometrician. He aims to facilitate a deeper meaning to health by discussing the importance of aural, sexual, and mental health.