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March 2016 continues upward HIV trend in Phl with 736 new cases

Seven hundred and thirty-sex (736) new HIV Ab seropositive individuals were reported to the HIV/AIDS & ART Registry of the Philippines this March, a number that – while lower than the February figure of 751 – was still 10% higher compared to the same period last year.

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Seven hundred and thirty-sex (736) new HIV Ab seropositive individuals were reported to the HIV/AIDS & ART Registry of the Philippines this March, a number that – while lower than the February figure of 751 – was still 10% higher compared to the same period last year (667). Of the new cases, most (97%) were male, with the median age of 28 years old (age range: eight years-63 years). More than half belong to the 25-34 year age group while 27% were youth aged 15-24 years.

The regions with the highest number of reported cases for March were: National Capital Region (NCR) with 284 (39%) cases, Region 4A with 94 (13%) cases, Region 3 with 82 (11%) cases, Region 7 with 71 (10%) cases, and Region 11 with 65 (9%) cases.

Reported modes of transmission were sexual contact (709), needle sharing among injecting drug users (IDU) [26], and mother-to- child transmission (1). Eighty-six percent (86%) of those transmitted through sexual contact were among males who have sex with males (MSMs).

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The effect of HIV among the youth continue to be even more defined, with the March data showing 204 (28%) cases involving youth aged 15-24 years. Most (96%) were male. Ninety-nine percent (203) were infected through sexual contact (17 male-female sex, 110 male-male sex, 76 sex with both males and females), and 1 (<1%) through needle sharing among IDU.

Also becoming even more defined is the emergence of those who engage in transactional sex as a key affected population. People who engage in transactional sex are those who report that they pay for sex, regularly accept payment for sex or do both. In March, 12% (90) of the reported cases engaged in transactional sex. Most (96%) were male (Table 4) whose ages ranged from 18 years-54 years (median: 28 years) while 4 were female whose ages ranged from 23 years-34 years (median: 25 years). Forty percent (35) of males who engaged in transactional sex were the ones who paid for sex while 2 of the females engaged in both.

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Also in March, there were 520 people living with HIV (PLHIV) who started taking antiretroviral medicine (as part of antiretroviral therapy). This was 16% higher than the same period last year (n=448). The median CD4 of these patients upon enrollment was 151 cells/mm3.

A total of 13,387 PLHIVs were presently on ART as of March 2016. Most (96%) were males. The median age of patients was 31 years (range: 11 months-77 years). Ninety-six percent were on first line regimen, 3% were on second line regimen and <1% were on mixed first and second line regimen.

For the month of March 2016, there were 26 reported deaths. Of the number, 92% (24) were male while 8% (two) were female. Fifteen (58%) of the reported deaths belong to the 25-34 year age group, eight were in the 35-49 year age group, two were youth aged 15-24 years old and one belongs to the 50 years and older age group. All were infected through sexual contact (four male-female sex, 14 male-male sex, eight sex with both males and females).

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Study suggests that after enrolling in HIV treatment program, less youth adhere to care regimens

Despite similar rates of enrollment into medical care, youth with HIV have much lower rates of viral suppression–reducing HIV to undetectable levels–compared to adults, according to an analysis funded by the National Institutes of Health

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Despite similar rates of enrollment into medical care, youth with HIV have much lower rates of viral suppression–reducing HIV to undetectable levels–compared to adults, according to an analysis funded by the National Institutes of Health.

Among more than 1,000 youth, most of whom were newly enrolled in care at treatment centers throughout the US, 12% had attained viral suppression, far lower than the 32% to 63% observed in studies of adults over age 24. The findings suggest that after they enroll in an HIV treatment program, a low proportion of youth adhere to care regimens. The study appears in the Journal of Acquired Immune Deficiency Syndrome.

“Our findings indicate an urgency for research on how best to tailor HIV intervention services to the needs of youth,” said the study’s first author, Bill G. Kapogiannis, M.D., of the Maternal and Pediatric Infectious Diseases Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The analysis was funded by NICHD, the National Institute on Drug Abuse and the National Institute of Mental Health.

The researchers analyzed data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), an NIH-supported network of 13 sites dedicated to the health and care of youth with and at risk for HIV. The youth were enrolled in care through the SMILE (Strategic Multisite Initiative for the Identification, Linkage and Engagement in Care of Youth) Collaborative, a network of clinics at each ATN site that offers diagnostic services and referral to treatment facilities.

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Among the 1,411 youth ages 12 to 24 years who were referred to the ATN sites, 75% were enrolled in care, with 34% remaining in care and beginning anti-HIV (antiretroviral) treatment and 12% achieving viral suppression after a median interval of nearly 5 months. Viral suppression occurs when antiretroviral therapy reduces a person’s HIV in the blood to an undetectable level. Maintaining viral suppression for at least 6 months after a person’s first test finds no detectable levels of the virus prevents the sexual transmission of HIV and allows people with HIV to remain healthy.

On average, youth who were referred to care within a shorter time frame after an HIV diagnosis were more likely to achieve viral suppression. Compared to youth referred to care after three months, those referred within one to six weeks were 2.5 times more likely to reach viral suppression. Those referred from six weeks to three months were roughly twice as likely to reach viral suppression.

To ensure the shortest possible time to enrollment in care, the study authors stressed the importance of enlisting trained peer counselors and of maintaining frequent contact with youth through text and social media messages. They added that additional strategies to ensure that youth enroll and remain in care are urgently needed.

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POZ

Vitamin E effective, safe for fatty liver in people with HIV

Vitamin E has been shown to improve fatty liver in the general population. A study now finds that Vitamin E is also beneficial to people living with HIV, who have a higher prevalence of fatty liver disease.

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A type of fatty liver disease that commonly affects patients with HIV can be safely treated with vitamin E, a McGill-led study has found.

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) and is characterized by liver inflammation and cell damage. It is a potentially dangerous condition that can progress to cirrhosis or liver cancer.

“Vitamin E has been shown to improve fatty liver in the general population,” says the study’s lead author Dr. Giada Sebastiani, Associate Professor in the Department of Medicine, McGill University and scientist at the Research Institute of the McGill University Health Centre. “Here we provide evidence for its beneficial effect and safety in people living with HIV, who have a higher prevalence of fatty liver disease.”

The study appears in the journal AIDS.

Dr. Sebastiani notes that NAFLD currently affects up to 48% of Canadians (alone) living with HIV and 25% of the general population, while NASH affects about one third of patients with NAFLD. There are several theories to explain the high prevalence of fatty liver among HIV-positive patients, explains Dr. Sebastiani: “It is possibly due to HIV-related inflammation, the antiretroviral drugs that they have to take lifelong, and to very frequent metabolic problems, such as diabetes and high lipids. Unfortunately, there is no approved therapy for fatty liver in people living with HIV.”

In the study, 27 patients with HIV and NASH were given vitamin E in an easily-tolerated dose of two pills per day. “We found that vitamin E improved both liver transaminases (the main blood tests for liver function) and liver fat measured by a non-invasive ultrasonographic test,” says Dr. Sebastiani. “These improvements were even more marked than those reported in the HIV-uninfected population.”

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Although she suspected vitamin E would reduce inflammation and fat in the HIV-positive group, Dr. Sebastiani was pleasantly surprised by the size of the effect.

Dr. Sebastiani notes that because the study did not have the benefit of a control group, and the study group was small and had a short follow-up (24 weeks), it’s considered a pilot project. “We would be interested in conducting a larger randomized controlled trial, with a longer follow-up,” she says.

Dr. Sebastiani came to McGill seven years ago from Italy with the goal of establishing a world-class research program focused on fatty liver and non-invasive diagnostic tools for liver disease. In the intervening years, cases of fatty liver disease, which was previously associated only with alcohol abuse, have exploded, particularly among obese Canadians. Dr. Sebastiani predicts that NAFLD will become the leading cause of liver transplants in the next 10 years.

“Vitamin E is an effective treatment for non-alcoholic steatohepatitis in HIV mono-infected patients” was written by G. Sebastiani, P. Ghali, M. Klein, et al.

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A new way to study HIV’s impact on the brain

Using a newly developed laboratory model of three types of brain cells, Penn and CHOP scientists reveal how HIV infection–as well as the drugs that treat it–can take a toll on the central nervous system.

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Though many negative repercussions of human immunodeficiency virus infection can be mitigated with the use of antiretroviral therapy (ART), one area where medical advances haven’t made as much progress is in the reduction of cognitive impacts. Half of HIV patients have HIV-associated neurocognitive disorders (HAND), which can manifest in a variety of ways, from forgetfulness and confusion to behavior changes and motor deficiencies.

To better understand the mechanisms underlying HAND, researchers from Penn’s School of Dental Medicine and Perelman School of Medicine and from the Children’s Hospital of Philadelphia (CHOP) brought together their complementary expertise to create a laboratory model system using three of the types of brain cells thought to be involved. Led by doctoral student Sean Ryan, who was co-mentored by Kelly Jordan-Sciutto of Penn Dental Medicine and Stewart Anderson of CHOP and Penn Medicine, the model recapitulates important features of how HIV infection and ART affect the brain.

“Frankly the models we generally use in the HIV field have a lot of weaknesses,” says Jordan-Sciutto, co-corresponding author on the paper, which appears in the journal Stem Cell Reports. “The power of this system is it allows us to look at the interaction between different cell types of human origin in a way that is more relevant to patients than other models.”

In addition to studying HIV, members of the team plan to use the same model to shed light on the neurological mechanisms that underlie other conditions, such as schizophrenia, Alzheimer’s, and even normal aging.

“We’re collaborating with a variety of colleagues to use this system to study Alzheimer’s disease as well as schizophrenia,” says Anderson, co-corresponding author on the paper. “We have the components in a dish that we know are interacting in these diseases, and this gives us a new mix-and-match way to understand how certain cells are contributing to neuronal damage.”

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Indeed, the impetus to create the model grew not out of HIV research but work that Ryan was pursuing in Anderson’s lab on schizophrenia.

“We had been looking at the role of microglia, the resident immune cells of the central nervous system,” says Ryan, first author on the work. “We wanted to see if we could see the mechanistic changes that occur with microglia in schizophrenia.”

To do so, Ryan and Anderson were interested in using human-induced pluripotent stem cells–adult cells that are reprogrammed to resemble embryonic stem cells–which can be coaxed into differentiating into a variety of different cell types.

But schizophrenia is a complicated disease with a variety of contributing genetic and environmental factors and a broad spectrum of presentations. Rather than looking at something complex, they sought to apply their new system to a disease that likewise causes neurological damage but does so in a more dramatic way and in which microglia are also implicated: HIV/AIDS infection.

They reached out to Jordan-Sciutto, who has deep experience investigating the mechanisms of HAND and was eager for the opportunity to develop a model superior to those currently available. Together, the scientists identified the three cell types they were most interested in studying: neurons, astrocytes, and microglia.

Neurons aren’t directly infected by HIV but are known to be damaged during infection. Meanwhile astrocytes are believed to interact with neurons, causing damage by sending pro-inflammatory factors into the spaces between cells, called synapses. And microglia, which are responsible for maintaining a healthy environment in the absence of disease, are seen to expand and contribute to inflammation during HIV infection.

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After nailing the technical challenge of creating this tractable model in which each cell type is generated independently and then mixed together, the team used it to probe how HIV infection and ART impact the cells, both alone and in combination.

“A lot of people are taking PreEP [pre-exposure prophylaxis] if they’re in a situation where their risk of contracting HIV is heightened,” says Ryan. “Just as we want to understand the cognitive impacts of HIV, we also want to see whether these drugs alone are impacting the brain health of otherwise healthy people.”

The researchers looked at RNA expression in their cultures to get a sense of what proteins and signaling pathways were becoming activated in each scenario. During infection, they saw inflammatory pathways that had previously been implicated in HIV in earlier research. When they introduced the antiretroviral drug EFZ, which is not in common use in the United States but remains a frontline therapy in many other areas of the world, with an infection, the activity of most of these pathways was reduced.

“But this scenario involved its own unique response,” says Ryan. Certain pathways associated with inflammation and damage remained despite the introduction of EFZ.

“EFZ treatment of the tri-cultures that included HIV-infected microglia reduces inflammation by around 70%,” Ryan says. Interestingly, EFZ by itself also triggered inflammation, though to a lesser extent than infection.

“It seems a combination of infection and ART is creating its own unique response that is different from the sum of its parts,” Ryan says. “Knowing what pathways are still active due to ART could help us appropriately target additional therapies so patients don’t develop HAND.”

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Many features of infection seen in the three-cell culture mirror what is known from HIV infection and ART treatment in people, giving the researchers confidence in the reliability of their model.

“Just looking at the microglia,” says Anderson, “we see in our system that they are taking on both of their normal roles in keeping key signaling systems balanced during their normal state and activating and causing damage when they’re fighting infection. We’re able to model normality and abnormality in a way we haven’t been able to before.”

For Jordan-Sciutto, the new system “is really going to change the way my lab operates going into the future.” She’s hopeful many other HIV scientists will take it up to further their studies as she also explores more aspects of HIV’s impact on the brain, such as how it navigates through the blood-brain barrier that normally protects the central nervous system from inflammation and infection.

The study authors give credit to the collaborative environment at Penn for this cross-disciplinary project. “Tentacles of this project extend from CHOP to the dental school to the vet school to the medical school,” says Anderson. “Penn is a very special place where people seem to be more likely to share their technologies around and let other people work with and develop them. This project is a great example of that.”

Kelly L. Jordan-Sciutto is vice chair and professor in the Department of Basic and Translational Sciences in Penn’s School of Dental Medicine, associate dean of graduate education, and director of biomedical graduate studies at the Perelman School of Medicine.

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PLHIVs battle access to meds during quarantine

The DOH stated that “treatment facilities shall ensure mechanisms are in place for the close coordination and communication between treatment facilities, partner organizations/support groups, and PLHIVs.” Meaning: PLHIVs ought to still coordinate with their respective hubs if these have efforts at all re access to treatment, care and support during the quarantine period.

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Designated treatment hubs and primary HIV care facilities are advised to “observe client-centered approach in the provision of antiretroviral (ARV) drugs to PLHIVs amid the imposition of Enhanced Community Quarantine and declaration of the entire Philippines under a state of calamity over Covid-19.”

DOH recognizes that “this current situation poses challenges in accessing life-saving medications… which may result in treatment interruption”, so it is mandating treatment facilities to “exhaust all possible methods to ensure reliable access to PLHIVs to treatment without having to risk increased exposure to Covid-19 when accessing their medicines.”

For the DOH, various methods recommended are:

  1. Use of available courier service for pick-up and delivery of ARVs. Cost of service may be shouldered by the treatment facility, the client, community-based organizations (CBOs), or PhilHealth’s OHAT package
  2. Hub-designated ARV access points (e.g. local government units or CBOs)
  3. Use of LGU vehicles for delivery of ARVs at agreed meeting points
  4. Use of electronic or SMS appointment information as proof of entry of PLHIVs in areas under community quarantine during extreme instances where visit to the primary treatment facility is inevitable

The DOH also emphasized the provisions of the Guidelines on Service Delivery of PLHIV Affected by the Community Quarantine, including the catering of affected PLHIVs by other treatment facilities for their ARV refills and for other services.

There is still confusion re access to treatment, however.

For instance, some facilities are reportedly requiring PLHIVs not under their care to bring their HIV confirmatory test results and their ARV booklets (that list down their ARV intake); but these requirements are with the primary hubs, not with the PLHIVs.

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In the end, the DOH is giving hubs leeway on implementation, stating that “treatment facilities shall ensure mechanisms are in place for the close coordination and communication between treatment facilities, partner organizations/support groups, and PLHIVs.”

Meaning: PLHIVs ought to still coordinate with their respective hubs if these have efforts at all re access to treatment, care and support during the quarantine period.

Some hubs reiterate the policy on co-sharing of responsibility – e.g. In a Facebook post, Dr. Jeffrey Garcia stated: “To all the patients from DOH-RITM ARG and other treatment hubs/primary HIV Clinics: You may temporarily have your ARV refill and medical consultations at a hub nearest to you.”

However, Garcia himself eventually noted that “there were incidents where PLHIVs/patients were not allowed to pass through the borders to have their ARV refill despite showing their IDs and cards” while “some cannot go the nearest hubs due to public transportation suspension.”

“I hope the DOH will address this soon”, just as he is asking other government agencies (e.g. Department of Social Welfare and Development, Armed Forces of the Philippines and local government units) to “please help our patients.”

Garcia added: “For now, you may seek assistance from your local government units/barangay officials.”

This, obviously, introduces other issues to PLHIVs – e.g. the need to unnecessarily disclose their HIV status so that other agencies will help them.

There are hubs that have been stepping up – e.g. Ospital ng Biñan – HIV/AIDS Core Team is conducting emergency ARV refill stations.

CBO The Red Whistle, meanwhile, partnered with MapBeks to create the Oplan #ARVayanihan map so those who want – or are able – to access other treatment hubs while the quarantine is in effect.

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In a Facebook post, Benedict Bernabe – who helms the group – stated that “because of road closures at borders between towns, cities, and municipalities, the paralyzation of the public transport system, the unreliability of courier services, the lack of viable documents that can be accepted at checkpoints, some PLHIVs are worrying about their supply of ARVs.” So the group created a map containing “ALL the DOH-designated treatment hubs across the country. This will give you the nearest treatment hub where you are located.”

The map also contains 1-km and 2-km area markers for PLHIV to check if the treatment hubs are within walking distance if there’s no transportation available.

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Immediate antiretroviral therapy makes HIV reservoirs in humans 100 times smaller

The initiation of ART at this very early stage leads to a drastic decrease in the size of viral reservoirs by clearing large pools of infected cells harboured in gut-associated lymphoid tissues and lymph nodes, which are known to be preferential sites for HIV persistence during ART.

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HIV hides in reservoirs during antiretroviral therapy (ART). These viral sanctuaries are the reason why ART is not a cure. And research teams have striven for years to determine how the HIV reservoirs are established and maintained during ART. Thanks to an unprecedented access to blood, and biopsies of rectums and lymph nodes of people at the earliest stages of HIV infection, an international team of researchers at the University of Montreal Hospital Research Centre (CRCHUM), the US Military HIV Research Program and the Thai Red Cross AIDS Research Centre has shown that the first established reservoirs are still “sensitive” during these early stages and could be downsized about 100 times upon immediate ART initiation.

In this study published in Science Translational Medicine, the researchers provide insight into the events unfolding during the crucial stages of early HIV infection. Through the U.S. Military HIV Research Program’s acute infection cohort, RV254/SEARCH010, which started 10 years ago in collaboration with the Thai Red Cross AIDS Research Centre, they identified acutely infected individuals in the first two weeks of infection (Fiebig I-II stages) and placed them onto ART immediately.

“The initiation of ART at this very early stage leads to a drastic decrease in the size of viral reservoirs by clearing large pools of infected cells harboured in gut-associated lymphoid tissues and lymph nodes, which are known to be preferential sites for HIV persistence during ART,” said Dr. Nicolas Chomont, a CRCHUM researcher and a professor at Université de Montréal.

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“Although the viral reservoirs from these early treated people are extremely small, the virus is still there and one might say there is no immediate clinical benefit for now. Nonetheless, since these early treated individuals have viral reservoirs 100 times smaller compared to our control group, we could reasonably think that it will be easier to eradicate these mini-reservoirs than the large reservoirs in people who started ART later.”

Louise Leyre, the study’s first author and a master student in Chomont’s lab at the time of the research, analyzed blood and tissues collected from individuals at the earliest stages of HIV infection to identify the locations in which HIV reservoirs are seeded and persist during ART. Previous studies in nonhuman primates had shown that the viral reservoirs can be found preferentially in lymphoid tissues.

“It was the first time researchers had access to blood, rectal and lymph node biopsies from the same people at this very early stage of infection,” said Dr. Chomont. “We owe these volunteers a lot.”

For this study, the researchers used samples from 170 acutely infected individuals in Thailand with a median age of 27, who initiated ART within a median time of 2 days after diagnosis. Ninety-six per cent (164) of the participants were male.

The researchers showed that participants starting ART at the earliest infection stages, known as Fiebig I to III, demonstrated a drastic decrease in the frequency of infected cells to nearly undetectable levels throughout the body. The rare infected cells that persisted were mostly found in their lymphoid tissues. Initiation of ART in infected individuals at later stages, i.e. Fiebig IV-V or chronic infection, induced only a slight reduction in the frequency of infected cells.

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According to the World Health Organization, approximately 37.9 million people were living with HIV at the end of 2018. The majority of what is known about HIV comes from research done in high-income countries, where HIV subtype B predominates. However, subtype B only accounts for 12 per cent of global HIV infections. Nearly 50 per cent of all people living with HIV have subtype C. In this study, HIV subtype AE, prevalent in the Southeastern Asia region, was investigated.

This research was supported by the U.S. Military HIV Research Program, Walter Reed Army Institute of Research; the Foundation for AIDS Research (amfAR Research Consortium on HIV Eradication); the Canadian Institutes of Health Research and the Fonds de Recherche du Québec-Santé.

“Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection” by Louise Leyre et al. appeared in Science Translational Medicine.

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Op-Ed

Covid-19 for people living with HIV

With persons living with HIV voicing their concerns regarding COVID-19, especially if their immunocompromised status makes them more vulnerable to the coronavirus, the AIDS Society of the Philippines provides the following advice for prevention.

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By AIDS Society of the Philippines

How can Persons Living with HIV protect themselves from COVID-19?

Recently, persons living with HIV have been voicing their concerns regarding COVID-19, especially if their immunocompromised status makes them more vulnerable to the coronavirus. The AIDS Society of the Philippines acknowledges and empathizes with the key affected population, and provides the following advice for prevention.

Adhere to ARV regimen

Continue to faithfully take your anti-retrovirals (ARVs) and ensure you have enough supply of ARVs. Reach out to your treatment hub, primary care facility, or community-based organization so they can help expedite your ARV refill despite the community quarantine in NCR. Call them to set an appointment before you visit.

Maintain a strong immune system

Continue to maintain a strong immune system with proper diet and enough sleep. Currently, there is no COVID-19 data specifically about persons who are immunocompromised. However, Dr. John Brooks from the HIV/AIDS Division of the CDC said publicly that, most likely, the risk for severe illness will be greater for persons at lower CD4 cell counts and those who aren’t virally suppressed.

Follow general precautions vs. COVID-19

Continue to follow DOH and WHO advice in COVID-19 prevention. This includes frequent handwashing, practicing cough hygiene, avoid touching the mouth, eyes, and nose, social distancing (maintain 3 feet distance), working from home, going out as little as possible, and seeking medical care when you have fever, cough, or difficulty breathing.

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If you have been exposed to a Person Under Investigation or Person Under Monitoring (PUI and PUM) for COVID-19, contact your treatment hub or primary care facility to request for advice. Home quarantine will likely be required, even without symptoms. If symptoms appear, visit your nearest government hospital for triaging and indicate the presence of co-morbidities.

Keep in touch with friends and family

Continue to take care of your mental health by reaching out and staying in touch with friends, family members, and support groups remotely or through the Internet. Social distancing doesn’t mean social isolation. But advise family and friends that due to your status, you have to limit your exposure to others. Finally, encourage other PLHIV and fellow Filipinos.

We stand with you in this difficult time. Stay strong—we will get through this together.

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