Signs and Symptoms of HIV Infection

The general course and presentation of HIV infection makes it tricky to describe the signs and symptoms of infection in the way you might with another infectious disease. The signs and symptoms of initial, acute infection mimic the flu so closely that testing and diagnosis are often missed. Then, HIV can progress in the body undiagnosed for years on end until a significant opportunistic infection arises and manifests with its own signs and symptoms. Once HIV infection has progressed to AIDS, the signs and symptoms are simply the signs and symptoms of the various opportunistic infections and cancers that occur.

Nevertheless, some signs and symptoms are associated with each stage of infection, and I've listed them here, for adults, based on WHO's clinical criteria for staging and reporting.

Primary HIV Infection (2-4 weeks post exposure)

Signs

Elevated viral load (rises quickly, then returns to baseline)

Low CD4+ T cell count (falls quickly, then returns to baseline)

Fever

Lymphadenopathy

Orogenital ulcers

Diffuse rash
Meningoencephalitis

Symptoms

"Feels like the flu"

Sore throat

Clinical stage 1: Asymptomatic

Signs

Low viral load

CD4+ T cell count >500

Persistent generalized lymphadenopathy

Symptoms
Generally asymptomatic

(This is an especially dangerous time--due to mildness (or even absence) of symptoms, the person is essentially asymptomatic and unlikely to seek out testing and treatment. They are at risk for uncontrolled progression as well as for spreading the disease to others.)

Clinical Stage 2: Mild Symptoms

Signs

Increased viral load

CD4+ T cell count between 350 and 499

Stage 2 Conditions
Moderate unexplained weight loss (<10% of normal body weight)
Recurrent respiratory tract infections (sinusitis, tonsilitis, otitis media, pharyngitis)
Herpes zoster (shingles)
Angular cheilitis (lesion at the corner of the mouth)
Recurrent oral ulceration
Rash
Seborrhoeic dermatitis (eczema-like)
Fungal nail infections

Clinical Stage 3: Moderate Symptoms

Signs

CD4+ T cell count 200-349

Stage 3 Conditions
Unexplained severe weight loss (>10% of normal body weight)
Unexplained chronic diarrhea > 1 month
Unexplained persistent fever > 1 month
Persistent oral candidiasis (thrush)
Oral hairy leukoplakia
Pulmonary tuberculosis
Severe bacterial infections (e.g. pneumonia, meningitis, bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis
Unexplained anemia, neutropenia, or chronic thrombocytopenia

Clinical Stage 4: Severe Symptoms, AIDS
Signs
Presumptive or definitive clinical diagnosis of any stage 4 condition AND confirmed HIV infection OR CD4+ T cell count<200

Stage 4 Conditions

HIV wasting syndrome
Pneumocystis pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection
Candidiasis of esophagus, trachea, bronchi, or lungs
Extrapulmonary tuberculosis
Kaposi's sarcoma
Cytomegalovirus infection
Central nervous system toxoplasmosis
HIV encephalopathy
Extrapulmonary cryptococcosis (e.g. meningitis)
Disseminated non-tuberculosis mycobacterial infection
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis with diarrhea
Chronic isosporiasis
Disseminated mycosis (coccidiomycosis or histoplasmosis)
Recurrent non-typhoidal Salmonella bacteremia
Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated tumors
Invasive cervical carcinoma
Atypical disseminated leishmaniasis
Symptomatic HIV-associated neuropathy or symptomatic HIV-associated cardiomyopathy

Resources
I found it interesting that information about signs/symptoms of HIV is not especially well-disseminated via the websites for WHO or the CDC. (WHO's main HIV information: http://www.who.int/features/qa/71/en/index.html. CDC's: http://www.cdc.gov/hiv/topics/basic/index.htm.)

I think this has to do with two things: first, that there is a move to "opt-out" testing, where everyone is tested routinely, rather than testing by signs/symptoms. Second, we know that the signs and symptoms of primary HIV infection mimic the flu.

Closer to home, WebMD publishes a list of signs and symptoms (http://www.webmd.com/hiv-aids/guide/hiv-symptoms) which seems a bit oversimplified/alarmist. Proceed with caution!

References

Lewis, Heitkemper, Dirksen, O'Brien, & Bucher. Human immunodeficiency virus infection. Medical-Surgical Nursing: Assessment and Management of Clinical Problems. Mosby, 2007.

World Health Organization (2007). WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Retrieved October, 2011 from: www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf

The Pathophysiology of HIV

The Short Version

Once human immunodeficiency virus (HIV) has entered the body, the virus replicates, primarily attacking lymphocytes called CD4+ T cells. Loss of these cells essentially destroys the immune system, leaving the client unable to fight off opportunistic infections. As viral load increases and CD4 cell counts drop, the danger increases. Primary cause of death is an opportunistic infection, such as respiratory arrest due to P. jiroveci pneumonia, with HIV as the underlying cause.

The Longer Version

HIV cannot replicate unless it is inside a living cell. To enter a CD4+ T cell, proteins on the envelope of the virus must bind with receptor sites on the cell. These proteins bind with CD4 receptors as well with chemokine receptors (specifically CXCR4 and CCR5 receptors, which will come up again when we talk about the relationship of genetics to HIV acquisition).

Once inside the cell, the virus begins the process of replication:

1. RNA is transcribed into DNA with help from an enzyme called reverse transcriptase.
2. The DNA strand copies itself and the two strands enter the cell's nucleus.
3. The DNA splices itself into the cell's genome with an enzyme called integrase. This means that HIV is now a permanent part of the cell. Every daughter cell will also be infected with HIV.
4. The cell produces HIV using the enzyme protease.
5. The new viruses exit the CD4 cell via budding, which eventually destroys the cell.

Here is a good illustration of viral replication, courtesy of NIAID. (Caveat: My numbering does not match theirs.)

Each step of viral replication, then, is an opportunity for treatment to stop replication. (We'll cover treatment in a future post.)

Initial infection is marked by both a high viral load and signs/symptoms resembling the flu. Then, the viral load drops for what can be a long period of time (up to ten years) without clinical symptoms. Two characteristics of this latent period make the virus especially insidious: First, an asymptomatic person is less likely to seek testing and treatment, heightening the risk that they will transmit the virus to others. Second, the virus replicates at such a fast pace that it mutates wildly, and this genetic variability hinders vaccine development.

A healthy adult has 800-1200 CD4+ T cells per microliter of blood; the immune system can function well with a CD4 count as low as 500. As HIV progresses, the body's ability to replace destroyed CD4+ T cells is overtaken by the ability of HIV to destroy those cells. When the CD4 count drops below 500, immune problems begin to occur, increasing in severity as the count continues to drop.

A client progresses to AIDS according to this classification system set out by the CDC; a person in Category 3 or Category C (or both) has AIDS. The system tracks CD4 count against the presence of opportunistic infection.

CD4 Counts	Clinical Categories
	A*	B**	C***
1. ≥500	A1	B1	C1
2. 200-499	A2	B2	C2
3. <200	A3	B3	C3

*Category A: Asymptomatic, acute HIV infection, or persistent generalized lymphadenopathy

**Category B: Symptomatic conditions that are not A or C. These are conditions attributed to HIV infection or immunosuppression; or they are conditions complicated by HIV infection. Some examples are: thrush, pelvic inflammatory disease, oral hairy leukoplakia, shingles, and peripheral neuropathy.

***Category C: AIDS-defining conditions. This long list of conditions includes: recurrent bacterial pneumonia, esophageal candidiasis, invasive cervical carcinoma, HIV-related encephalopathy, chronic herpes simplex, Kaposi's sarcoma, P. jiroveci pneumonia, progressive multifocal leukoencephalopathy, toxoplasmosis of the brain, and wasting syndrome (involuntary loss of more than 10% of body weight with chronic diarrhea).

References

1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. MMWR, December 18, 1992. Retrieved October 2011 from: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm

HIV Replication Cycle. NIAID, 2010. Retrieved October, 2011 from: http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/pages/hivreplicationcycle.aspx

Lewis, Heitkemper, Dirksen, O'Brien, & Bucher. Human immunodeficiency virus infection. Medical-Surgical Nursing: Assessment and Management of Clinical Problems. Mosby, 2007.

Primary HIV-1 infection: Pathogenesis; epidemiology and clinical manifestations. Up to Date, 2011. Retrieved October, 2011, from: http://www.uptodate.com.offcampus.lib.washington.edu/contents/primary-hiv-1-infection-pathogenesis-epidemiology-and-clinical-manifestations?source=search_result&search=hiv+pathophysiology&selectedTitle=1~150

Epidemiology of HIV in Mozambique

First, some background on HIV

Human immunodeficiency virus (HIV) is the virus that causes acquired immune deficiency syndrome (AIDS). HIV is transmitted via specific bodily fluids (blood, semen, vaginal secretions, and breast milk); common forms of transmission are sexual intercourse or sharing needles with an infected person. The virus attacks the immune system, destroying a specific type of white blood cell called CD4 and thus reducing a person's ability to fight off infection and cancer. Though great strides have been made in treatment of HIV, there is no vaccine and no cure.

The 30-year anniversary of the HIV/AIDS epidemic passed in June of this year. On June 5, 1981, the CDC first reported on cases of a rare pneumonia in five otherwise healthy young gay men in Los Angeles. By 1985, every region of the world had reported a case of HIV/AIDS, and by 1988 more women than men were living with HIV/AIDS in sub-Saharan Africa.

The advent of rapid HIV testing (1992) and highly active antiretroviral therapy (HAART, 1995) reduced mortality rates in the U.S., but by 2000 it was clear that the burden of the epidemic had shifted resoundingly to the developing world. Today it is estimated that sub-Saharan Africa is home to 60% of all HIV-infected adults and 90% of HIV-infected infants. Almost 25 million people in sub-Saharan Africa are living with HIV, and nearly 3 million are newly infected each year.

Next, some background on Mozambique

The Republic of Mozambique lies on the Indian Ocean in southeastern Africa, bordered by Tanzania to the north and South Africa to the south. The Portuguese arrived in the early 1500s to colonize it. Mozambique became independent in 1975 and promptly fell into a disastrous civil war that lasted until the early 1990s. Since then, Mozambique has struggled to emerge from poverty and take advantage of its resources. The population today is around 22 million; the per capita gross income is US$440; life expectancy at birth is 48.

Epidemiology of HIV in Mozambique: Prevalence

UNAIDS/WHO's most recent estimates show the prevalence of HIV in Mozambican adults at 12.5%. (As contrast, prevalence in the U.S. is <1%.) One hundred thousand children are infected. Mortality continues to rise, with an estimated 81,000 people dying in 2007.

Prevalence varies geographically. Larger urban centers (such as Maputo and Beira) show HIV prevalence in pregnant women (chosen for "sentinel surveillance") at an alarming 25-39%, while prevalence rates in rural areas can be as low as 1-5%.

One of the most dramatic stories in Mozambique is the number of "AIDS orphans"—children who have lost both parents to AIDS. UNAIDS/WHO estimates that as of 2007 there are over 400,000 children who have lost their parents in Mozambique.

Epidemiology of HIV in Mozambique: Access to Care

Access to care is a significant issue for Mozambicans. The UN estimates the prevalence of contraception of any method at 16.5%, and of condoms at 1.1%. UNAIDS/WHO estimates that less than 50% have access to facilities that provide HIV testing and counseling.

Only 90,000 people receive antiretroviral therapy, though it is estimated that almost 400,000 should be on the medications—that is, less than 25% of those people who need antiretroviral therapy are receiving it. These numbers have improved over time, but it is clear that further "ramping up" is necessary.

Progress is being made in preventing mother-to-child transmission. In 2003, only 3% of the pregnant women received antiretrovirals; by 2007 this number was up to 46%.

Epidemiology of HIV in Mozambique: Health Education

The following data is from 2003, and I can only hope that things have changed over the intervening years. A study demonstrated that less than 30% of young people (defined as 15-24) could correctly name two ways of preventing HIV transmission and reject two misconceptions. Less than 20% of those who had more than one partner over the previous 12 months reported use of a condom during the most recent intercourse.

References

Choi R, Farquhar C. AIDS, Epidemiology and Surveillance. In: Heggenhougen K, Quah S, eds. International Encycolopedia of Public Health. Vol. 1. San Diego: Academic Press, 2008:76-90.

Kaiser Family Foundation. The global HIV/AIDS epidemic: a timeline of key milestones. Retrieved October, 2001, from: http://www.kff.org/hivaids/aidstimeline

UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance. Epidemiological fact sheet on HIV and AIDS, Mozambique, 2008 update. Retrived October 2011 from:

UNICEF. Mozambique statistics. Retrived October, 2011, from: http://www.unicef.org/infobycountry/mozambique_statistics.html#73

Hello!

Welcome to my blog for NSG 521, Infectious Disease and Infection Control.

My name is Susan. I'm a recently minted RN moving on to a master's in (ready?) Advanced Practice Community Health Systems Nursing, Cross-Cultural and Global Health. I'm also in the graduate certificate program in HIV and STIs.

I'm interested in HIV specifically as a global health issue. I've worked with refugee populations and in resource-constrained settings, and I'm looking forward to learning more about how to reduce transmission risk and implement successful treatment in these areas.

For this blog, I've chosen to focus on HIV in Mozambique. I spent a few weeks in Mozambique this summer working in a small clinic in Beira, and can't wait to get back there someday. Here's a photo of the consultório from my POV.