Slide 2
Over 15 years into the HIV pandemic, the developing world continues to
bear the greatest burden of this disease. Based on UNAIDS data through the
end of the year 2000, this panel shows the estimated number of adults and
children newly infected with HIV during 2000 by region. Sub-Saharan Africa
had the largest number of new infections, followed by South and South-East
Asia. Overall, it is estimated that there were 15,000 new infections each
day, with over 95% of these in the developing world. Of newly infected
adults, 47% were women and over 50% were in 15-24 year olds.
Slide 3
In addition to the direct effects of HIV/AIDS as a cause of disease and
death, a related tragedy is the number of children who have been orphaned
by the death from AIDS of their mother or both parents. Again, Sub-Saharan
Africa has suffered the most from this calamity with over 12 million
children orphaned by the end of 1999.
Slide 4
When regional statistics concerning individuals living with HIV/AIDS
are examined, considerable differences both in total numbers and in the
percentage of adults who are HIV-infected are seen. These differences are
related to the population sizes in these regions, to the differing ages of
the epidemic in different areas and to the differences in local
epidemiology, particularly the risk factors for the spread and
transmission of HIV. In Sub-Saharan Africa, the epidemic began in the
later 1970s and HIV has been primarily spread through heterosexual
transmission; on the other hand, in Eastern Europe and Central Asia the
epidemic began in the later 1990s and has been spread primarily through
injection drug use. In other geographic areas, transmission has occurred
through varying combinations of heterosexual contact, injection drug use,
and men having sex with men.
Slide 5
Globally, sexual transmission, primarily heterosexual, is the
predominant mode of HIV transmission. Magnitude of risk varies with
different types of sexual activity. Receptive vaginal intercourse is
associated with a risk of 0.1-0.2% per episode. The risk with receptive
anal intercourse is somewhat greater and the risk with insertive vaginal
or anal intercourse is somewhat lower. Although the risk with oral
intercourse is low, there is now data to suggest that this may account for
a significant minority of transmissions, particularly with sex between
men.
Slide 6
The second major mode of transmission is parenteral contact, through
blood or blood product transfusion, injection drug use, or, more
uncommonly, with needle stick exposure of health care workers. Transfusion
is a particularly efficient means of transmission with 95% chance of
infection when a single unit of HIV-infected whole blood is transfused.
Risk per exposure from injection drug use is significantly lower.
Perinatal transmission is the third major type of transmission with a
baseline risk of 25-30% in the absence of antiretroviral drugs and
accessibility to scheduled Cesarean section. The degree of risk with
traditional practices, such as female circumcision, using non-sterile
instruments is unknown.
Slide 7
The CD4+ T lymphocyte, a type of white blood cell, is a primary target
of the human immunodeficiency virus and measurement of these cells is the
major indicator of immune system function in an individual infected with
HIV. With initial infection the CD4 cell count, normally greater than 1000
cells/mm3, drops precipitously. As the body's immune defenses bring the
infection under some degree of control, the CD4 count begins to rise
again, recovering in different degrees in different individuals based on
their individual immune response. However, over time and in the absence of
antiretroviral therapy, CD4+ T lymphocytes are depleted at a fairly steady
rate of approximately 50 cells/year. When the CD4 count drops below 200
cells/mm3, the infected person is defined as having AIDS and is at
increasing risk for the opportunistic infections which are the primary
cause of death in individuals with HIV infection.
Slide 8
Measurement of HIV-RNA, also known as the viral load, is performed on
fresh or fresh-frozen plasma or serum and is a powerful and accurate
indicator of prognosis in HIV infection. It is very useful in determining
response to antiretroviral therapy, drugs which directly fight HIV.
HIV-RNA levels suggest how much the virus is multiplying, and are very
high with acute infection. Over the first few weeks to months the
HIV-specific immune response begins to control the intensity of viremia
and a "viral set-point" is established, which varies by
individual, and reflects a steady state between viral replication and
elimination. This viral set point is highly predictive of the rate of
future progression of illness, with higher viral set points associated
with more rapid decline in CD4 cell counts and more rapid occurrence of
clinical disease. Without treatment, HIV-RNA levels gradually increase,
and as end-stage HIV disease approaches, viral loads tend to increase more
rapidly and to high levels.
Slide 9
This graph superimposes key clinical landmarks of HIV infection on the
CD4 cell count and HIV-RNA levels over time. A transient symptomatic
illness can be identified in 40-90% of cases of primary HIV infection. The
signs and symptoms of acute HIV infection are non-specific and mimic those
of many acute viral illnesses. The most frequently reported clinical
manifestations include fever, fatigue, rash, headache, lymphadenopathy,
pharyngitis, night sweats, mild gastrointestinal upset, and oral
ulcerations. This syndrome is accompanied by wide dissemination of virus
and viral seeding of lymphoid organs, and is a time of high infectivity.
After clinical symptoms resolve, the HIV-infected person enters a period
of clinical latency, which usually lasts for a number of years. During
this time, she is asymptomatic and may not know she is infected and at
risk for transmitting infection to others. Eventually, with progressive
failure of the immune system, general or constitutional, usually
nonspecific symptoms, such as fever, weight loss, and night sweats, again
develop. With further decline in CD4 cell counts, generally to levels less
than 200 cells/mm3, the woman is at risk for the opportunistic infections
and malignancies that are the hallmark of AIDS and the direct cause of
death in patients with AIDS.
Slide 10
We have just talked about the epidemiology and the natural history of
HIV infection and have seen that, while it is truly a global problem, the
areas hardest hit have limited resources to fight this disease. And yet,
many individuals at risk for HIV do not think they are at risk. Based on a
series of local surveys, this bar graph represents the proportion of 15-19
year old sexually active women in different countries who did not think
they were at any risk of acquiring HIV infection.
Slide 11
However, when the actual HIV prevalence in women attending antenatal
clinics in these same countries is examined, there is frequently a
significant difference between perception and reality. For example, in
Zimbabwe, where 30% of women attending antenatal clinics in major urban
areas are HIV-infected, half of sexually active young women do no think
they are at risk at all, when in fact all women should think themselves
"at risk". This underscores the importance of education on a
wide scale basis to convey accurate information about HIV, to counter or
dispel misperceptions and myths, and most importantly, to promote
prevention. We know how to prevent this infection and the means to prevent
HIV are available in high and low resource areas alike..
Slide 12
In order to provide appropriate care for the woman with HIV, it is
first important to make the diagnosis of HIV infection. In areas where HIV
testing resources are scarce, health care providers may suggest HIV
testing because of signs or symptoms suggestive of HIV disease or because
of high risk characteristics noted on risk assessment. Pregnant women are
a priority for counseling and voluntary testing because of greater
availability of effective short-term antiretroviral therapies to reduce
the risk of mother-to-child transmission. A diagnosis of HIV remains the
cause of significant stigma and discrimination. Testing should be
voluntary and results should be confidential. Pretest counseling should
include information about HIV transmission and natural history, the
testing process and meaning of test results, and a private discussion of
personal risk characteristics and risk reduction.
The most commonly used HIV assays detect antibodies to the virus in
blood but results are generally not available until 1-2 weeks later.
Unfortunately, studies have shown that typically fewer than 50% of
individuals tested return for results, particularly in areas where travel
to and from a clinic is difficult. A good alternative in certain
circumstances is the use of rapid tests, a number of which are now
available internationally; these tests are easy to perform in the field
and some require as little as 5 minutes to obtain results, making it
possible to test and give results at a single visit. Most rapid tests are
very accurate, with 95-100% sensitivity and specificity.
It is also important to counsel the individual after testing has been
done and results are available in order to give and interpret results, to
reinforce risk reduction plans in HIV-negative individuals, to educate
HIV-infected individuals about prevention of transmission to others, and
to link persons who are infected with needed services.
Slide 13
Voluntary counseling and testing or VCT is an entry point for
prevention and care for HIV-infected individuals. This includes helping
the infected person begin to accept the fact of their infection and plan
for the future; promoting and facilitating prevention of further
transmission, such as with condom use; providing access to early medical
care and management of infections; making reproductive health care
available, including sexually transmitted infection screening and
treatment and access to family planning; providing maternity services to
reduce mother-to-child transmission; and encouraging support from family
and the community. VCT can also be a point of entry for services and care
for HIV-negative individuals, who may still be at high risk for infection
and need access to medical care and prevention.
Slide 14
The goals of care for individuals with HIV who live in limited resource
settings are no different from the goals of care for those with HIV who
live in areas where a full range of antiretroviral and other therapies are
available. These goals are:
- To improve the quality of life and reduce suffering
- To prolong life And to prevent transmission to others
Slide 15
There are several medical interventions that can help achieve these
goals. Good nutrition is important to prevent micronutrient deficiencies,
such as folate and vitamin A deficiency; and to offset weight loss. Anemia
has been shown to be an independent predictor of progression and death in
HIV infection; therefore, prevention or correction of anemia with proper
nutrition, prevention of postpartum hemorrhage, and treatment of malaria
and other parasitic diseases will help prolong life in the HIV-infected
person. Ability to prevent and treat opportunistic infections is limited
by drug availability. UNAIDS currently recommends prophylaxis against two
specific types of infection, pneumocystis pneumonia or PCP and
tuberculosis or TB in HIV-infected individuals meeting certain criteria.
These infections can be prevented using inexpensive medications that are
more likely to be available and accessible in low-resource settings. In
the case of tuberculosis, prophylaxis is important not only in the
management of HIV but also for the prevention of active tuberculosis and
transmission of tuberculosis. Individuals dually infected with both TB and
HIV are at a 50-100 times greater risk of developing active tuberculosis.
Although antiretroviral drugs are not yet generally available in
limited resource settings for the treatment of HIV, they may be available
for short-term use for prevention of mother-to-child transmission. In the
developed world these drugs have been responsible for dramatic reductions
in morbidity and mortality from HIV in infected individuals and major
declines in rates of mother-to-child transmission.
Slide 16
The most common HIV-related conditions, with the exception of
tuberculosis, are associated with exposure to organisms that are often
found in the daily environment but do not pose a danger to individuals
with healthy immune systems. These are known as opportunistic illnesses
and they generally occur late in the course of HIV infection when the
immune system is badly damaged. Oral candidiasis or thrush is the most
frequently found HIV-associated condition globally, although there are
significant variations from country to country. In Africa, tuberculosis is
the most common opportunistic infection. In limited resource settings,
these conditions represent major challenges because of inadequate
diagnostic techniques and lack of affordable or available drugs for
treatment.
Slide 17
There are several gynecologic problems that are common in the setting
of HIV infection and these often occur when the woman with HIV has no
other symptoms. In one study almost one-half of HIV-infected women
developed a gynecologic problem over the course of follow-up and another
study of hospitalized AIDS patients found that 83% of women had coexisting
gynecologic disease. These include menstrual disorders, genital ulcer
disease, abnormal vaginal discharge, pelvic inflammatory disease, and
human papillomavirus infections and lower genital tract dysplasia and
neoplasia. Several of these conditions are more frequent or more severe
with declining immune function; others may be associated indirectly with
HIV because of common risk behaviors, weight loss, or other factors.
Slide 18
An important aspect of care for the HIV-infected woman is provision of
appropriate contraception to prevent unintended pregnancy. Considerations
for contraceptive choice include safety and efficacy; in addition,
noncontraceptive benefits, such as reduction of menstrual bleeding with
hormonal methods, may have additional benefits in correction or prevention
of anemia. In addition, a very important consideration is the effect of
contraceptive methods on HIV and sexually transmitted infection,
transmission or acquisition. Both male and female condoms offer the most
significant protection against HIV transmission and STI acquisition and
should be a part of any contraceptive regimen.
Slide 19
Sexually transmitted infections or STIs and HIV are closely
interrelated. The clinical findings of certain STIs are changed in the
presence of HIV. Furthermore, STIs, both ulcerative and nonulcerative,
increase the risk of transmission of HIV 2-5-times. Genital ulcers disrupt
the epithelial barrier, and STIs also increase the number of cells
vulnerable to HIV, increasing susceptibility to HIV in uninfected
individuals. On the other hand, HIV-infected persons with STIs have
increased genital tract HIV viral load, increasing infectiousness.
Treatment of these infections reduces the amount of virus in the genital
tract. These findings suggest that screening and treating sexually
transmitted infections can be another way to prevent HIV transmission.
Indeed, in one clinical trial in Tanzania, enhanced syndromic management
of STIs resulted in a 38% decrease in HIV seroconversion over two years.
Slide 20
For HIV-infected women who are pregnant or considering pregnancy, there
are special issues that need to be addressed. These issues should also be
discussed with women of unknown status in areas of high HIV prevalence or
women who are at high risk for other reasons. The magnitude of the risk of
mother-to-child transmission and current interventions to prevent this
transmission should be discussed using the most up-to-date information and
considering what resources are available, including information on
antiretroviral agents, if these are accessible. In addition,
infant-feeding options to balance infant health and risk of transmission
through breastfeeding must be addressed. Disclosure of her HIV status to
sexual partners who do not know she is infected should be discussed and
facilitated, if possible, after assessment of potential risks of violence
for the woman. Condom use should be encouraged throughout pregnancy for
prevention of transmission of HIV to sexual partners, as well as to
prevent acquisition of STIs. Other infant care issues, including future
care for infants who are uninfected, are important to discuss. Finally,
for women who have an undesired pregnancy, termination of pregnancy may be
an option if available legally and safely.
Slide 21
There are several maternal and obstetrical risk factors which have been
identified as potentially increasing, or in some cases, decreasing the
likelihood of mother-to-child transmission. Factors relating to HIV
infection itself which increase the risk of transmission include more
advanced clinical disease, lower CD4 cell count, and perhaps most
significantly higher HIV-RNA levels, both in the blood and in the genital
tract. Certain maternal behavioral or physiologic factors, such as
unprotected sex with multiple partners, cigarette smoking, and substance
abuse have been implicated in increased risk of transmission.
Slide 22
Furthermore, the presence of STIs or other coinfections, or vitamin A
deficiency have been implicated in the increased risk of transmission.
Several different antiretroviral regimens beginning late in pregnancy or
at the onset of labor have shown effectiveness in reducing mother-to-child
transmission, including a very inexpensive regimen with a single dose of
nevirapine to both mother and newborn. Most transmission occurs around the
time of labor and delivery; preterm delivery, placental disruption with
abruption or chorioamnionitis, invasive fetal monitoring, and prolonged
duration of membrane rupture have been associated with increased risk of
transmission. Scheduled Cesarean section, prior to the onset of labor or
rupture of membranes, appears to reduce the risk of transmission, but must
be balanced against maternal risk with operative delivery. Finally,
breastfeeding carries significant risks of mother-to-child transmission,
especially in mothers newly infected in pregnancy or postpartum:
breastfeeding may account for over 50% of new pediatric HIV cases globally
each year. Although some of these factors cannot be altered, others
provide the opportunity for intervention, even in limited resource
settings.
Slide 23
In the absence of access to specific treatments for HIV, progression of
disease appears to be inevitable and eventually a range of nonspecific
signs and symptoms develop which significantly reduce quality of life.
Pain, similar to that seen in cancer patients, is the most prevalent
symptom and requires prompt and aggressive treatment.
Slide 24
These medications are part of the list of essential drugs assembled by
UNAIDS. They include some simple and relatively inexpensive drugs to
manage symptoms seen in late stage HIV disease to reduce suffering and
improve remaining life quality.
Slide 25
An important part of the comprehensive care of the individual with HIV
infection is prevention of further transmission to others. There are a
number of factors that affect sexual transmission of HIV, in terms of both
infectiousness and susceptibility. Both late HIV disease and primary HIV
infection increase infectiousness, probably related to increased levels of
viremia in both plasma and genital tract. Genital tract infections
increase local viral shedding and increase infectiousness and
susceptibility. Menstruation in women and the lack of a foreskin in
uncircumcised males have also been linked with increased risk of both
transmission and acquisition of HIV. Pregnancy, the use of hormonal
contraception, and the presence of cervical ectopy have been linked in
some studies with increased viral shedding in the genital tract, as well
as potentially increased susceptibility. Barrier contraceptive methods,
specifically condoms reduce both infectiousness and susceptibility.
Spermicides have in vitro activity against HIV, but a recent clinical
trial conducted by UNAIDS found that nonoxynol-9 users had an increased
rate of HIV seroconversion as compared to regular lubricant users,
probably related to increased rates of irritation and mucosal trauma with
frequent use. Although data are unclear regarding infectiousness with
intrauterine device or IUD use, this method has been associated with
increased susceptibility and is not an optimal method for women at
increased risk for HIV.
Slide 26
This information can be used to counsel women about secondary
prevention of transmission, with a focus on low risk behavior, consistent
use of condoms, and STI prevention and treatment. For those who are
injection drug users, prevention of secondary transmission includes drug
treatment, if available; avoiding the sharing of needles or other drug
equipment or high-level disinfection of injection works after use, if
sharing continues. All injection drug users should be taught how to safely
dispose of needles after use to avoid accidental needle sticks.
Slide 27
There is a lot of stigma and fear associated with HIV among health care
workers. It's important for health care workers to better understand what
their risks are and what they aren't. The highest risks for HIV
transmission are associated with exposure to blood, serum, semen, vaginal
secretions, and sputum. Percutaneous exposure with needlestick or other
break in integrity of the skin carries the highest risk, approximately
0.4% per single needlestick. This is followed by mucocutaneous exposure to
mouth or eyes from splashes of blood or other body fluids, with an
approximate risk of 0.09% per exposure. Exposures to intact skin carry a
theoretical but undocumented risk. Other risk factors relate to the
quantity of blood to which the health care worker is exposed and how sick
the source patient is. As noted earlier, individuals are most infectious
both very early and very late in the course of their disease. The health
care workers own immune system plays an unclear role in risk of infection.
Finally, post-exposure prophylaxis, if available and easily accessible,
may decrease risk after an exposure.
Slide 28
There are some simple things that can be done for infection prevention
related to HIV in the health care setting. The use of personal protective
equipment, including gloves, gowns, and face and eye protection, is
important during the performance of surgery, obstetrical deliveries and
other procedures. Handwashing both before and after any contact with blood
or other body fluids is necessary. Needles and other sharp instruments
should be handled carefully and disposed of safely in containers designed
for that purpose. Instruments should be appropriately disinfected after
use and tissues and other contaminated items should be disposed of
carefully. When available, hepatitis B vaccination should be encouraged
for all health care workers to prevent acquisition of hepatitis B, which
is much more easily transmissible than HIV.
Slide 29
In conclusion, although countries with limited resources bear the
greatest burden of HIV disease, there are important, simple, and
inexpensive interventions that can be employed to care for individuals
with HIV, to relieve their suffering and provide comfort and improved
quality and quantity of life, while reducing further spread of HIV.
