Symptoms By Mayo Clinic staff

Friday, July 3, 2009

The symptoms of HIV and AIDS vary, depending on the phase of infection.

Early infection
When first infected with HIV, you may have no signs or symptoms at all, although it's more common to develop a brief flu-like illness two to four weeks after becoming infected. Signs and symptoms may include:

• Fever
• Headache
• Sore throat
• Swollen lymph glands
• Rash

Even if you don't have symptoms, you're still able to transmit the virus to others. Once the virus enters your body, your own immune system also comes under attack. The virus multiplies in your lymph nodes and slowly begins to destroy your helper T cells (CD4 lymphocytes) — the white blood cells that coordinate your entire immune system.

Later infection
You may remain symptom-free for eight or nine years or more. But as the virus continues to multiply and destroy immune cells, you may develop mild infections or chronic symptoms such as:

• Swollen lymph nodes — often one of the first signs of HIV infection
• Diarrhea
• Weight loss
• Fever
• Cough and shortness of breath

Latest phase of infection
During the last phase of HIV — which occurs approximately 10 or more years after the initial infection — more serious symptoms may begin to appear, and the infection may then meet the official definition of AIDS. In 1993, the Centers for Disease Control and Prevention (CDC) redefined AIDS to mean the presence of HIV infection as shown by a positive HIV-antibody test plus at least one of the following:

• The development of an opportunistic infection — an infection that occurs when your immune system is impaired — such as Pneumocystis carinii pneumonia (PCP)
• A CD4 lymphocyte count of 200 or less — a normal count ranges from 800 to 1,200

By the time AIDS develops, your immune system has been severely damaged, making you susceptible to opportunistic infections. The signs and symptoms of some of these infections may include:

• Soaking night sweats
• Shaking chills or fever higher than 100 F (38 C) for several weeks
• Dry cough and shortness of breath
• Chronic diarrhea
• Persistent white spots or unusual lesions on your tongue or in your mouth
• Headaches
• Blurred and distorted vision
• Weight loss

You may also begin to experience signs and symptoms of later stage HIV infection itself, such as:

• Persistent, unexplained fatigue
• Soaking night sweats
• Shaking chills or fever higher than 100 F (38 C) for several weeks
• Swelling of lymph nodes for more than three months
• Chronic diarrhea
• Persistent headaches

If you're infected with HIV, you're also more likely to develop certain cancers, especially Kaposi's sarcoma, cervical cancer and lymphoma, although improved treatments have reduced the risk of these illnesses.

Symptoms of HIV in children
Children who are HIV-positive may experience:

• Difficulty gaining weight
• Difficulty growing normally
• Problems walking
• Delayed mental development
• Severe forms of common childhood illnesses such as ear infections (otitis media), pneumonia and tonsillitis

When to see a doctor
If you think you may have been infected with HIV or are at risk of contracting the virus, seek medical counseling as soon as possible. Questions to consider include:

• Why should you get tested? The idea of being tested for HIV infection may be frightening. But testing itself doesn't make you HIV-positive or HIV-negative, and it's important not only for your own health but also to prevent transmission of the virus to others. If you engage in a high-risk behavior such as unprotected sex or sharing needles during intravenous drug use, get tested for HIV at least annually.
• What if you're pregnant? If you're pregnant, you may want to get tested even if you think you're not at risk. If you are HIV-positive, treatment with anti-retroviral drugs during your pregnancy can greatly reduce the chances you'll pass the infection to your baby.
• Where can you get tested? You can be tested by your doctor or at a hospital, the public health department, a Planned Parenthood clinic or other public clinics. Many clinics don't charge for HIV tests. Be sure to choose a place in which you feel comfortable and that offers counseling before and after testing. Don't let concern about what people may think stop you from being tested. For a referral, or to make an appointment for an HIV test at a Planned Parenthood clinic near you, call 800-230-PLAN (800-230-7526). You can also contact your local or state health department.
• Will your results be private? All states and U.S. territories report positive HIV and AIDS test results to state public health officials to help track the spread of the disease. Most states use name reporting, but the results are released only to the health department and not to anyone else — including the federal government, employers, insurance companies and family members — without your permission. In addition, legal provisions ensure the highest degree of confidentiality with regard to name-based HIV data. If you are concerned about having your name reported, many states offer anonymous testing centers. If you do test positive and seek treatment, however, you will likely have to provide your name to your doctor.

Scientists now trying to outflank HIV/AIDS virus

Wednesday, July 1, 2009

WASHINGTON – Like a general whose direct attacks aren't working, scientists are now trying to outflank the HIV/AIDS virus.

Unsuccessful at developing vaccines that the cause the body's natural immune system to battle the virus, researchers are testing inserting a gene into the muscle that can cause it to produce protective antibodies against HIV.

The new method worked in mice and now has proved successful in monkeys, too, they reported Sunday in the online edition of the journal Nature Medicine. The team is led by Dr. Philip R. Johnson of the Children's Hospital of Philadelphia.

That doesn't mean an AIDS vaccine for people is in the wings, Johnson said. Years of work may lie ahead before a product is ready for human use.

Nevertheless, the report was welcomed by Dr. Beatrice Hahn, an AIDS researcher the University of Alabama at Birmingham, who was not part of Johnson's team. "It basically shows there is light at the end of the tunnel," she said in a telephone interview.

"It shows thinking outside the box is a good idea and can yield results, and we need perhaps more of these nonconventional approaches," she added.

According to the International AIDS Vaccine Initiative, AIDS is one of the most devastating pandemics. More than 20 million people have died so far and about 33 million are living with HIV. The Center for Disease Control and Prevention last year estimated there are about 56,000 new HIV infections annually in the United States.

Most efforts at blocking AIDS have sought to stimulate the body's immune system to produce antibodies that fight the disease. This model has worked for diseases such as measles and smallpox. It hasn't done as well with HIV/AIDS; test vaccines have failed to produce a protective reaction.

So Johnson decided to try something different.

"We used a leapfrog strategy, bypassing the natural immune system response that was the target of all previous HIV and SIV vaccine candidates," Johnson said. HIV, or human immunodeficiency virus, causes AIDS in people. The closely related simian virus, or SIV, affects monkeys.

"Some years ago I came to the conclusion that HIV was different from other viruses for which we were trying to develop vaccines and we and might not ever be able to use traditional approaches," Johnson said in a telephone interview.

He said the researchers knew there were proteins that could neutralize the HIV virus, so they began thinking about whether they could use them to fight the disease.

In a decade-long effort, Johnson, K. Reed Clark of Nationwide Children's Hospital in Columbus, Ohio, and their team developed immunoadhesins, antibody-like proteins designed to attach to SIV and block it from infecting cells.

Then they needed a way to get the immunoadhesins into the cells.

The researchers selected the widely used adeno-associated virus as the carrier because it is an effective way to insert DNA into the cells of monkeys or humans. That virus was injected into muscles, where it carried the DNA of the immunoadhesins. The muscles then began producing the protective proteins.

Scientists first tested the idea in mice and then turned to monkeys because SIV is closely related to HIV and would be a good test model.

A month after administering the AAV, the nine treated monkeys were injected with SIV, as were six not treated in advance.

None of the immunized monkeys developed AIDS and only three showed any indication of SIV infection. Even a year later they had high concentrations of the protective antibodies in the blood.

All six unimmunized monkeys became infected; four died during the experiment.

The next step is moving toward human trials, Johnson said. He said he is working with the International AIDS Vaccine Initiative in hopes of getting tests in humans under way in the next few years.

The research was supported by the National Institute of Allergy and Infectious Diseases.

Definition of Human immunodeficiency virus

HIV, the cause of AIDS. HIV has also been called the human lymphotropic virus type III, the lymphadenopathy-associated virus and the lymphadenopathy virus. No matter what name is applied, it is a retrovirus. (A retrovirus has an RNA genome and a reverse transcriptase enzyme. Using the reverse transcriptase, the virus uses its RNA as a template for making complementary DNA which can integrate into the DNA of the host organism). Although the American research Robert Gallo at the National Institutes of Health believed he was the first to find HIV, it is now generally accepted that the French physician Luc Montagnier (1932-) and his team at the Pasteur Institute discovered HIV in 1983- 84.

Fighting the Virus: Treatment Options for HIV and AIDS

Though it is not possible to comletely eliminate HIV from the body, the goal of treatment is to keep the virus from reproducing. This is important because many studies have shown that people with high levels of virus in the blood (the viral load) will progress more rapidly to AIDS. The goal is achieve a viral load test that shows undetectable levels of HIV (the virus never goes away, just goes to very low levels). When the virus is not reproducing quickly, it is less likely to kill CD4 cells. As the CD4 cell count increases, the immune system regains strength.

When to start treatment

The International AIDS Society–USA is an organization that specializes in keeping physicians informed about the latest research in HIV/AIDS. It recommends that patients start taking antiviral medications (anti-retrovirals) before the CD4 count falls below 350 cells per cubic milliliter of blood. The exact timing of treatment depends on many factors, and doctors and patients should discuss the risks and benefits before starting therapy.

If the decision is made to start treatment, your doctor will choose a combination of anti-retrovirals to fight your HIV infection. Several medications must be used together—often called a drug cocktail or highly active anti-retroviral therapy (HAART). These medications attack HIV at multiple points in its growth cycle and are more effective in suppressing the virus. Combining drugs also limits the risk that HIV will become resistant to these medications. When HIV becomes resistant to antivirals, these drugs become much less effective in controlling the virus.

Anti-retroviral drugs

There are more than 20 anti-retroviral medications available in the United States today. Many of these come in combination form, making the total number of different "pills" available closer to 30. These drugs have two or three names and may be referred to by the generic name, trade name, or a three letter abbreviation (for example, AZT is also known by its generic name, zidovudine, and by its trade name, Retrovir). Currently available anti-retroviral drugs include:

• Nucleoside reverse transcriptase inhibitors (NRTIs) block HIV reproduction at the virus' "reverse transcriptase." Examples include zidovudine (Retrovir, AZT), didanosine (Videx, ddI), stavudine (Zerit, d4T), abacavir (Ziagen, ABC), emtricitabine (Emtriva, FTC) and lamivudine (Epivir, 3TC) Tenofovir (Viread) is a commonly prescribed drug in a related family (nucleotide reverse transcriptase inhibitors). There are many NRTI combination pills including lamivudine and zidovudine (called Combivir) and emtricitabine and tenofovir (called Truvada).
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act on the same HIV reverse transcriptase that the NRTIs block, but at a different location. Drugs in this class include nevirapine (Viramune) and efavirenz (Sustiva)
• Protease inhibitors (PIs) block the assembly of new HIV virus particles (they inhibit the virus' "protease"). Atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase), and Tipranavir (Aptivus) are all Pis. PIs are often "boosted" with ritonavir to increase potency. Lopinavir and ritonavir are combined into one pill (Kaletra) for this purpose.
• Cell entry blockers block the virus at the cell surface. A fusion inhibitor called enfuvirtide (Fuzeon) and a CCR5 co-receptor antagonist, called maraviroc (Selzentry), are currently the only medications available that block HIV from getting inside the cell in the first place. Enfuvirtide is only available in injectable form.
• Integrase inhibitor. Raltegravir (Isentress) is the only medication available today that blocks the "integration" of the virus’ genetic material with the cell’s genetic material. This blocks HIV from reproducing inside the cell.

Which drugs are right for you?

Numerous combinations can be made depending on patient and doctor preference. Because many of these drugs have side effects, such as nausea and diarrhea, the exact medications prescribed for a particular person may depend on side effects (which will vary from person to person).

The most commonly recommend initial therapy is a combination of the NNRTI efavirenz (Sustiva) and two NRTIs. A potential choice for people who are likely to miss doses of medication is a combination pill called Atripla. It contains efavirenz, emtricitabine, and tenofovir. Atripla is taken as one pill, once per day.

It is very important to tell your doctor about ALL other medications you take (including herbals and non-prescription medication) because there can be serious interactions with commonly used medications. Also, no one should take an anti-retroviral medication that was not specifically prescribed for them by a health care provider.

In addition to anti-retrovirals, people with low CD4 counts should take drugs to prevent the development of opportunistic infections. For example, people with CD4 cell counts below 200 cells per milliliter of blood should take trimethoprim-sulfamethoxazole (known as Bactrim or Septra) to protect themselves against

Protein Mimics Trap HIV Virus in a Cellular Box

06 December 2007 - HIV has killed over 25 million people since its emergence in late 1981. The virus’ resilience comes from mutations – there could be thousands of different HIV strains in a single patient, each with their own resistance to treatments. Research teams from the University of Zurich and the University of Washington have potentially developed a new class of drugs to treat the pandemic Human Immunodeficiency Virus

All HIV strains are RNA lentiviruses that attack the same way, regardless of how often they mutate. First, the virus injects viral RNA into the host cell. Then, using viral reverse transcriptase, it creates DNA that is incorporated into the host’s own genetic code. This reverse transcription process is error-prone and can leave many mutations. This is one of the main reasons why HIV mutates so rapidly, making it so difficult to treat.

However, this study shows that the mechanism also represents an HIV weak spot. Viral DNA, once copied into the cell nucleus, can not leave and must export RNA molecules in order to have an effect. Since the virus is not native to the cell, the transport process must be carried out by another viral protein, called Rev.

The team, led by Professor John A. Robinson, target Rev binding sites on the viral RNA through the use of a peptide mimetic. These peptides ‘mimic’ the structure of a target protein and firmly bind to Rev responsive elements (RRE) on the viral RNA, thereby inhibiting Rev binding. Without Rev, viral RNA cannot leave the host nucleus and the virus is effectively trapped within the host cell and will not be able to cause any further damage.

Previous efforts to find RRE inhibitors have been met with limited success. “Hairpin peptide mimetics are a highly promising new class of drugs,” says Dr. Robinson. Mimetics provide one novel way to target drug-resistant strains of HIV as RRE’s are a very common feature of the HIV virus.

Whether such mimetic treatment plans will prove effective in the long run remains to be seen. Further research into effectiveness and delivery is currently underway.

Written by Charley Wang
Reviewed by Andrew Wang
Published by Pooja Ghatalia.

Infection with Hepatitis C Virus among HIV-Infected Pregnant Women in Thailand

1Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA 30341-3717, USA
2Thailand MOPH-U.S. CDC Collaboration, CDC, Nonthaburi 11000, Thailand
3Faculty of Medicine Siriraj Hospital, Mahidol Univeristy, Siriraj, Bangkoknoi, Bangkok 10700, Thailand
4Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
5Queen Sirikit National Institute of Child Health, Department of Medical Services, Ministry of Public Health, Bangkok 10400, Thailand
6Department of Public Health Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
7Department of Medical Services, Rajavithi Hospital, Ministry of Public Health (MOPH), Bangkok 10400, Thailand
8Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA





Received 5 March 2008; Revised 28 June 2008; Accepted 3 November 2008

Recommended by Daniel Landers





Abstract

Objective. The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women. Methods. Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV. Results. Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51–14.25%). Conclusions. HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women.


1. Introduction

Worldwide, the hepatitis
C virus (HCV) seroprevalence rate among pregnant women is approximately 1% [1]. This is similar to the 1.6% prevalence of HCV
antibody in the general population in the United States
[2]. Among HIV-infected pregnant women, much
higher prevalences of HCV positivity have been reported, ranging from as high
as 30 to 50% in some settings [3, 4], particularly in populations with high
rates of injection drug use.

Although the
perinatal transmission rate of HCV is estimated to be less than 5% among
HIV-uninfected women, it is generally higher in HIV-infected women [1]. Not all studies, however, have found
increased HCV transmission rates among HIV-infected women [5] and a wide range
of estimates of the risk of vertical transmission of HCV among coinfected women
has been reported with wide geographic variation [6, 7].

The purpose of this study was to
describe the epidemiology of coinfection with hepatitis C virus and HIV among a
cohort of pregnant Thai women.
2. Materials and Methods

The current study
population includes 1771 women previously enrolled in three vertical
transmission studies in Bangkok,
Thailand [8–10] who had
specimens available for HCV testing.
From the first study (peri-1), 342 HIV-uninfected women and 293 HIV-infected
women are included. From the second
(peri-2) and third studies (peri-3), 391 and 745 HIV-infected women are
included, respectively. Women in these
studies were either enrolled during antenatal care (peri-1 and 2) or at
delivery (peri-3). All children born to
HIV-infected women were followed
for 4–18 months and
their mothers did not breastfeed. No
follow-up information is available for infants born to HIV-uninfected women in
peri-1. Peri-1 was an observational prospective
cohort study without treatment interventions, peri-2 was a randomized
placebo-controlled clinical trial assessing the efficacy of short-course
zidovudine prophylaxis antenatally and
intrapartum, and peri-3 was an observational
study of short-course zidovudine and single-dose nevirapine propylaxis. All three studies were conducted jointly by
the Thailand Ministry of Public Health and the U.S. Centers for Disease Control
and Prevention (CDC) at two large Bangkok
hospitals from 1992 to 2004. The three
perinatal studies (peri-1,2,3) and this current retrospective laboratory study
were all approved by the institutional review boards at the CDC in Atlanta and
the Ethical Review Committees for Research in Human Subjects at the Thailand
Ministry of Public Health and Siriraj Hospital in Bangkok.

In the original
studies, specimens were collected and tested for HIV, HIV viral load, CD4 count
as previously described [8, 9]. Stored
plasma specimens from pregnancy or delivery were screened for antibodies to HCV
(anti-HCV) using enzyme immunoassay (EIA; Abbott Murex version 4.0, Abbott Laboratories, Abbott Park, Ill USA).
All positive EIAs were tested with qualitative reverse transcriptase
polymerase chain reaction (RT-PCR; Ampliscreen, Roche Diagnostic Systems, Branchburg, NJ,
USA). If the qualitative RT-PCR was negative, the
plasma specimen was retested with recombinant immunoblot assay (RIBA 3.0,
Chiron Corporation, Emeryville,
Calif, USA). All women who were EIA positive and either
qualitative RT-PCR or RIBA positive are considered HCV infected (either current
or past); all other women are considered HCV uninfected. All specimens with detectable virus were
tested with quantitative PCR (COBAS Amplicor HCV Monitor Test, version 2.0,
Roche Diagnostic Systems) with a lower limit of detection of <600
copies/mL. All women with detectable
virus are considered to have active HCV infection. Specimens with detectable HCV were genotyped
using the Trugene HCV 5′NC genotyping kit (Bayer HealthCare LLC, Berkeley, Calif,
USA) and
sequence analysis with the OpenGene DNA sequencing system. Results were then confirmed using sequence analysis (ABI
PRISM 310 Genetic Analyzer, Applied Biosystems, Calif,
USA)
methods. In 8 cases where the results from
the two techniques were discordant, the 715 nt E1-E2 region at position
883-1597 nt was directly sequenced.

Stored plasma from
infants born to women coinfected with HIV and HCV was also tested for HCV. An HCV-infected infant was defined as an
infant who was anti-HCV positive (i.e., EIA-positive with confirmatory RIBA) at
18 months of age or older or who had positive HCV RNA on two occasions. Several serial samples from infants were
tested, depending on availability of samples and testing results, since HCV
infection often cannot be excluded in infants by one-time testing [11]. However, due to limited availability infant
specimens, 18/48 (37.5%) of infants tested had testing at only one time point.

Statistical analyses
were performed using SAS software version 9.1 (SAS Institute, Cary, NC, USA). Odds ratios with 95% confidence intervals
were estimated using unconditional logistic regression, adjusting for the three
perinatal studies. Ninety-five percent confidence intervals for HCV
transmission rates were estimated using exact binomial
methods.
3. Results

There were low rates of intravenous drug use
(1.5%) among the 1771 women included in this study (Table 1). A higher proportion of women reported several
other risk factors for hepatitis C acquisition, including having an injection
drug-using partner (10.2%) and ever having been a commercial sex worker
(7.8%). HIV-infected women had
moderately high CD4 counts at delivery (mean 428 cells/mm3); the
mean viral load at delivery was 10 000 copies/mL.
tab1
Table 1: Demographic and clinical characteristics of
1771 women enrolled in 3 vertical transmission HIV studies
in Bangkok, Thailand, 1992–2004 (n (%)).

Among 1429 HIV-infected pregnant women 62 (4.3%)
were found to have HCV antibodies by EIA.
Of those, 54 had positive confirmatory testing by either RT-PCR
(n=43) or by RIBA (n=11). Thus, 3.8%
(54/1429) of HIV-infected pregnant women were found to be coinfected with HCV
and 3.0% (43/1429) had evidence of
active infection. Among 342
HIV-uninfected women, 2 (0.6%) were found to have HCV antibodies by EIA. Of those, only one of the women had positive
confirmatory testing by RT-PCR. Thus, 0.3% (1/342) of HIV-uninfected
pregnant women were found to be infected with HCV.

Among the 54
HCV-seropositive women, 22 did not receive any antiretroviral prophylaxis, 22
received 4 weeks of antenatal zidovudine and intrapartum zidovudine, and 10
received 4 weeks of antenatal zidovudine and intrapartum zidovudine and
nevirapine. Of the 43 HIV-infected women with quantifiable HCV, the serum
levels of HCV RNA were as follows: 12 women with <100 000 copies/mL, 17
women with 100 000–850 000
copies/mL, and 13 women with >850 000 copies/mL. One woman who was HCV RNA-PCR positive on the
qualitative assay had undetectable virus (<600 copies/mL) on the
quantitative assay. The HIV-uninfected
woman with quantifiable HCV had a serum level of HCV of 62 000 copies/mL. The HIV-infected women in later cohorts
(peri-2 and peri-3) were more likely to be HCV infected (4.1 and 4.4%, resp.)
compared with HIV-infected women in the earlier cohort (1.7%) (see Table 1). Among the 35 HCV-infected women with
confirmed HCV genotyping results, 14 (40%) were genotype 3a, 14 (40%) were
genotype 1a, 4 (11.4%) were genotype 1b, 2 (5.7%) were genotype 6a, and 1 (2.9%)
was genotype 4a.

In unadjusted
analyses, factors associated with pregnant women being HCV infected included more
education, intravenous drug use, having a partner with a history of injection
drug use, ever having been a commercial sex worker, and having received a blood
transfusion. These risk factors remained significant when
adjusting for perinatal study (Table 2).
In a multivariate model adjusted
for all covariates in Table 2, only three factors remained significant: intravenous drug use (adjusted odds ratio
70.5; 95% CI 24.8–201), having a partner with a history of injection drug use
(adjusted odds ratio 3.4; 95% CI 1.5–7.4), and having received a blood
transfusion (adjusted odds ratio 6.7; 95% CI 1.9–23.9). Since HIV-uninfected women were only included
in peri-1, we included only women in peri-1 when estimating the odds of HCV
infection by HIV status. This study did
not find an association between HIV infection status and HCV infection (adjusted
odds ratio 5.9; 95% CI 0.7–51.0).
tab2
Table 2: Odds of
being HCV-infected among 1771 pregnant women enrolled in 3 vertical transmission HIV studies in Bangkok, Thailand, 1992–2004.

For peri-1, all 5 infants born to HIV/HCV-infected
women had samples tested for HCV RNA at 2, 4, and 6 months and no infants were
found to be HCV infected. For peri-2,
12/16 infants had 6-month samples available which were tested for HCV RNA and 13/16
infants had 18-month samples available which were tested for HCV
antibodies. All infants had testing from
at least one time point and 10 infants were tested at more than one time point. From peri-2, one infant was HCV-RNA positive
at 6 months; additional testing of a 4-month sample from this infant confirmed
that this infant was HCV-RNA positive.
In addition, three infants were anti-HCV positive by EIA at 18
months. However, only one of these
infants had positive confirmatory testing by RIBA. For peri-3, 15 infants had serial testing at
both 2 and 4 months and 27 infants had testing performed for at least one time point.
No infants were found to be HCV infected.

In summary, among 48 infants tested for HCV
who were born to HIV/HCV coinfected women, two infants were HCV infected for an
HCV transmission rate of 4.2% (95%  0.51–14.25%). One of these infants was born to a woman who was
infected with HCV genotype 3a and had an HCV viral load of 764 323 copies/mL
and an HIV viral load of 2092 copies/mL.
The mother of this infant received zidovudine for 4 weeks antenatally and
during labor; this infant was HIV uninfected.
The other infant was born to a woman who was infected with HCV genotype
1a and had an HCV viral load of >850 000 copies/mL and an HIV viral load of
20 342. The mother of this infant did
not receive any antiretroviral prophylaxis; this infant was HIV infected.

The HIV vertical transmission rate among
infants born to the 1429 HIV-infected women was 12.9% (Table 3). There was a 9.4% (5/53) HIV transmission rate among
HCV-infected mothers and a 13.0% (170/1306) HIV transmission rate among HCV-uninfected
mothers (P=.445). The odds of an
infant being HIV infected did not differ significantly by the mother’s HCV
status neither in unadjusted
analyses (odds ratio 0.70; 95% CI 0.27–1.77), nor in analyses adjusted for perinatal
study (adjusted odds ratio 0.82; 95% CI 0.32–2.12).
tab3
Table 3: HIV/HCV status and clinical characteristics
of infants born to 1429 HIV-infected women enrolled in 3 vertical transmission of HIV
studies in Bangkok, Thailand, 1992–2004 (n (%)).
4. Conclusions

HCV infection in pregnancy is
emerging as an increasingly important issue.
Due to improved HCV blood screening, mother-to-child transmission of HCV
has now replaced transfusion-associated transmission as the predominant mode of
spread in children [1]. In this retrospective
analysis of more than 1700 pregnant women in Thailand, most of whom were HIV infected,
we found relatively low hepatitis C seroprevalence rates. Among the HIV-infected pregnant women, HCV
seroprevalence was 3.8% and active HCV infection was 3.0%. Among HIV-uninfected pregnant women, HCV
seroprevalence was 0.3%. The low rate of
injection drug use in the population (1.5%) likely accounts for this relatively
low HCV seroprevalence, which is only slightly higher than many general
populations of pregnant women who are HIV uninfected. (1) In a study conducted in Thailand
from
1993-1994 among a
convenience sample of 120 HIV-infected women, 6.7% were anti-HCV positive by EIA
[12]. In another study in Thailand
in
1991, 2.7% of 883 women admitted to the hospital with gynecologic abnormalities
had HCV antibodies [13]. Among Thai
women reporting injection drug use, higher HCV prevalence rates have been
reported, with 15% of 200 female injection drug users HCV infected in a recent
study [14].

The risk factors for HCV infection identified, which included more education,
intravenous drug use, having a partner with a history of injection drug use,
ever having been a commercial sex worker, and having received a blood
transfusion, were similar to risk factors associated with HCV in prior studies
[15]. Although the number of
HIV-uninfected women was small in this study, we did not find HIV infection to
be a significant risk factor for HCV infection. As expected, a history of
injection drug use was the strongest predictor of HCV infection (adjusted OR
126; 95% CI 48.6–326), similar to other studies among blood donors which have also
identified injection drug use as a strong risk factor for HCV infection [15]. There are six major HCV genotypes, which are
numbered 1–6 and subtyped a, b, and
c. Type 1b is the most common genotype
worldwide. Types 1a and 3a, which were
the predominant genotypes in the present study, are largely associated with
injection drug use [16, 17].

In the United States,
routine HCV screening is recommended for persons with certain high-risk
characteristics (e.g., history of injection drug use or blood transfusion) and
for children born to HCV-infected women [18].
However, routine screening is not recommended for pregnant women without
other risk factors [19]. U.S.
guidelines
also recommend that HIV-infected persons be routinely screened for HCV [20]. In Thailand, although current national
guidelines do not address routine HCV screening or hepatitis testing for
HIV-infected patients, most physicians provide hepatitis testing for
HIV-infected adults with symptoms or risk factors, and pediatric providers in
tertiary care centers often test HIV-infected children who are at risk. Pregnant women in antenatal clinics are also
routinely screened for hepatitis B, but not HCV. HCV treatment is available in Thailand
at cost to patients
or to patients with private health insurance.

The HCV perinatal
transmission rate among infants born to HIV/HCV coinfected women in this study was
4.2%. However, due to the small number
of HCV-infected women in our sample, the confidence interval was wide. The estimated frequency of HCV transmission
in this current study is similar to those of two recent multicenter studies conducted among
mostly HIV-uninfected women in the United States [21] and Europe [22] which reported
transmission rates of 3.6% and 6.2%, respectively. Since HIV-infected women in
this cohort had relatively high CD4 counts at delivery, it is not clear how
generalizable these findings are to other cohorts of HIV-infected pregnant
women. Although the published literature
has shown a correlation of maternal HCV viral load and the risk of HCV vertical
transmission [4, 23], there were too few HCV mother-to-child transmission in
our study to draw conclusions. However, both
HCV-infected infants born to HIV-infected women had high HCV viral loads.
Acknowledgments

The authors wish to thank the TUC laboratory staff for their
outstanding work processing and testing all the specimens, and Daniel Newman
for his extensive assistance with data management for the study. This study
received funding from the Opportunistic Infections Working Group at the Centers
for Disease Control and Prevention. The findings and conclusions in this
article are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.

Focusing On The HIV Virus: £1.7M Award To Develop Nanotechnology For Use In Health Care

Scientists at the University of Liverpool have been awarded £1.7 million to investigate how nanotechnology could be used to improve the effectiveness of pharmaceutical drugs.

Nanotechnology involves the manipulation of matter at sizes close to molecular level to produce particles that are small clusters of molecules. The collaborative project between the Departments of Chemistry and Pharmacology will apply nanotechnology techniques to develop new approaches for future drug development.

Many medicines currently in use have poor solubility and have to be administered in large doses to ensure that enough of the drug is absorbed into the body to be effective. Scientists, working closely with industry experts, will investigate the possibility of creating viable drugs in nanoparticle form - each particle being approximately 1/800th the width of a human hair. By examining how successfully they can be absorbed into the intestine, and in what form they pass into the bloodstream, they will also look to establish if nanotechnology can reduce the toxicity of drugs by using smaller doses without losing effect.

The project will focus on the HIV virus - the incurable disease that can lead to AIDS. There are more than 20 HIV medicines already on the market, which aim to prevent AIDS by ensuring that the disease cannot replicate uncontrollably in the body. It is important to maintain efficacy while avoiding excessively high or low doses that allow the development of resistance to the drugs. HIV drugs are a lifelong commitment and the doses currently needed have significant associated toxicity when administered over a lifetime. Complications include heart problems, osteoporosis and visible fat redistribution.

Professor Steve Rannard, from the University's Department of Chemistry, said: "Control of matter on this nano-scale is gathering global interest and several new nano-medicines are now commercially available. Our approach will use existing drugs but will focus on changing their size rather than their chemistry. We aim to control their activity and the ability to target the drug to areas where the virus is usually inaccessible.

"Our close collaboration with industry partners and advisors will ensure that we maximise the opportunities available through nanotechnology and, more importantly, that we improve current methods of healthcare for the benefit of patients."

Dr Andrew Owen, from the University's Department of Pharmacology, said: "We aim to improve the activity of currently available drugs but safety is at the forefront of this research, which involves the Medical Research Council Centre for Drug Safety Science.

"We will explore the hypothesis that less medicine is needed in nano-form and hope to prove that creating nano-drugs could enhance their ability to kill the HIV virus while reducing their toxicity. We will look closely at how much of each drug gets into the bloodstream and into different cells and hope to confirm that the nano-medicines are not toxic to their target cells or to the body as a whole."

The three-year project will be undertaken in collaboration with industry partners Astra Zeneca; Merck, Sharpe and Dohm; Gillead; Abbott; and Iota NanoSolutions.

The funding, awarded by Research Councils UK, forms one area of the Nanotechnology Grand Challenges scheme - designed to investigate how nanotechnology could be beneficial to a range of areas such as health, energy and the environment.

Source:
Laura Johnson
University of Liverpool

The STI Files: Human Immunodeficiency Virus (HIV)

Stat: About 1 out of every 250 people in the United States carries the HIV virus according to current estimates, and women are the group hardest hit globally by HIV and AIDS.

What is it exactly? HIV is a virus that destroys the immune system and thus weakens the body's ability to fight disease and infection, even common infections like flus and colds. HIV usually progresses to AIDS. This makes HIV the most dangerous sexually transmitted infection today. It is the fifth leading cause of death for the young under 40 in the United States. At this time, no one has been cured of HIV or AIDS.

About how many people have it? About 40,000 people in the United States become infected with HIV every year.

How is it spread? Through body fluids (namely blood, semen, penile and vaginal secretions and breast milk -- HIV can be present in saliva, but kissing and other general exposures to saliva are not known to present risks of transmission) through anal and vaginal intercourse or oral sex, shared needles used for injecting IV drugs or accidental pricks with infected needles, blood transfusions, childbirth or breastfeeding.

What are its symptoms? Initial or acute infection may have symptoms that resemble mononucleosis or the flu within 2 to 4 weeks of exposure, but in many people, HIV infection does not show any symptoms for extended periods of time, and for some, is asymptomatic for as long as 20 years.

For those who experience symptoms, they may inluce: sore throat or mouth sores, aching or stiff muscles or joints, headaches, diarrhea, swollen glands, fevers, persistent fatigue or tiredness, rashes or excema, yeast infections, rapid weight loss or chronic PID.

How is it diagnosed? By a blood test which screens for antibodies. Because it can take up to three months or more of the antibodies to appear, a negative test should always be reapeated, and an annual or semi-annual HIV screening is advised.

Is it treatable? Yes, through an intensive combination of antiviral drugs and consistent health care. HIV treatment acts to try and protect the immune system from further infection, and to delay the progression to AIDS.

Is it curable? There is no cure for HIV.

Can it effect fertility? It cannot affect fertility, but is very commonly transmitted from mother to child during pregnancy or childbirth.

Can it cause death? Any severe compromise of the immune system can cause death, and if HIV infection becomes acute or progresses to become AIDS, it is fatal. Most HIV infections do progress to AIDS.

How can we protect against it? By using condoms ALWAYS for vaginal intercourse, anal intercourse or oral sex. HIV can also be prevented by decreasing your number of sexual partners, by avoiding high-risk sexual practices like anal sex or oral-anal sex or unprotected vaginal or oral sex, by avoiding sex with those who use intravenous drugs and by not participating in IV drug use yourself, by disallowing urine to come into contact with the mouth, anus, eyes, or open cuts or sores, and by getting annual or semi-annual HIV screenings, and insisting your partners do likewise.

HIV-Like Virus Found in Gorillas

A form of HIV has been found in wild gorillas in western central Africa. This is the first time the AIDS-causing virus has been detected in primates other than chimps and humans. It is also the "first time someone has looked at HIV infection in wild living gorillas," said Martine Peeters, a virologist at the French government's Institut de Recherche Pour le Développement and at the University of Montpellier, France.

"We found they were infected—and to our surprise are infected with a virus which is closely related to the one we find in chimpanzees and also in humans."

Simian immunodeficiency virus (SIV) was detected in gorilla populations more than 250 miles (400 kilometers) apart, suggesting that SIV may be common and widespread in the lowland gorilla subspecies.

Peeters is the lead author of a study published today in the journal Nature. She says chimpanzees may have transmitted the virus to gorillas.

Reservoir Species

The gorilla virus is closely related to HIV-1 group O, one of three HIV groups known to infect humans.

A different viral strain, HIV-1 group M, is responsible for the current global HIV/AIDS pandemic. Some 40 million people are currently infected, and an estimated 25 million have died of AIDS.

The team of international scientists used antibody tests and RNA analysis on hundreds of chimp and gorilla fecal samples collected in the remote forests of Cameroon (Cameroon map, facts, and music). RNA, or ribonucleic acid, helps control chemical activities in cells.

Researchers did not survey the mountain gorilla subspecies, which lives in East Africa.

Earlier this year the same team reported that the chimpanzees in southeast Cameroon were the primary reservoir of the HIV-1 group M virus.

At the time, the researchers also suggested the chimps were the reservoir for a second, less common HIV-1 strain known as group N. Group N is currently responsible for only about ten human HIV cases in Cameroon. The HIV-1 group O virus, though, is responsible for about one percent of current human HIV cases in Cameroon. Until the latest study, group O had not been found in nonhuman primates. Peeters says it is still too early to say whether western lowland gorillas are a reservoir species or merely a carrier of the virus.

But she believes chimpanzees could have infected gorillas with the group O virus in the distant past.

More than 30 primate species are known to carry SIV viruses, the study authors note.

But—unlike HIV-positive humans—chimps, gorillas, and other primates that carry SIV do not appear to suffer illness.

Peeters says a goal now "is to find out how [HIV] moved—when, how, and which animal transmitted it to humans."

Such findings could better explain the processes that drive some viruses to leap from animals to humans and cause global disease pandemics, while other outbreaks remain restricted to small populations, Peeters says.

"What we would like to know now is, [is] this virus circulating in chimpanzees and gorillas? How [have these] been transmitted from one species to another? What happens amongst humans when there is cross-species transmission?"

Biologist Eddie Holmes studies virus evolution at Pennsylvania State University in University Park.

Holmes described the new study as "extraordinary."

"I guess I ruled out gorillas as a carrier of HIV," he said, adding that "it is amazing to learn that there is a new primate carrier of HIV."

He thinks the findings are also significant because they further illuminate the diversity of the HIV virus in natural populations and the processes by which these viruses jump species.

"If you look at the rise of HIV, there's been a jump from chimpanzees to humans," Holmes said. He attributes the transfer of HIV to logging and to trading wild animal meat, both activities that bring humans into close contact with ape and monkey flesh. (See a "bush meat" photo gallery—warning: graphic images.)

Holmes says growing human interaction with wild species—as a result of changing land use, deforestation, global travel, war, famine, and the expansion of cities—will provide more opportunities for new viruses to emerge.

Human Papilloma Virus And Cancer, HIV Discoveries Recognized In 2008 Nobel Prize In Physiology Or Medicine

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2008 with one half to: Harald zur Hausen for his discovery of "human papilloma viruses causing cervical cancer" and the other half jointly to Françoise Barré-Sinoussi and Luc Montagnier for their discovery of "human immunodeficiency virus."

This year's Nobel Prize awards discoveries of two viruses causing severe human diseases.

Harald zur Hausen went against current dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer, the second most common cancer among women. He realized that HPV-DNA could exist in a non-productive state in the tumours, and should be detectable by specific searches for viral DNA. He found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer. His discovery has led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis and the development of prophylactic vaccines against HPV acquisition.

Françoise Barré-Sinoussi and Luc Montagnier discovered human immunodeficiency virus (HIV). Virus production was identified in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunodeficiency, and in blood from patients with late stage disease. They characterized this retrovirus as the first known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment.

Discovery of human papilloma virus causing cervical cancer

Against the prevailing view during the 1970s, Harald zur Hausen postulated a role for human papilloma virus (HPV) in cervical cancer. He assumed that the tumour cells, if they contained an oncogenic virus, should harbour viral DNA integrated into their genomes. The HPV genes promoting cell proliferation should therefore be detectable by specifically searching tumour cells for such viral DNA. Harald zur Hausen pursued this idea for over 10 years by searching for different HPV types, a search made difficult by the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.

Importance of the HPV discovery

The global public health burden attributable to human papilloma viruses is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population. Of the more than 100 HPV types known, about 40 infect the genital tract, and 15 of these put women at high risk for cervical cancer. In addition, HPV is found in some vulval, penile, oral and other cancers. Human papilloma virus can be detected in 99.7% of women with histologically confirmed cervical cancer, affecting some 500,000 women per year.

Harald zur Hausen demonstrated novel properties of HPV that have led to an understanding of mechanisms for papilloma virus-induced carcinogenesis and the predisposing factors for viral persistence and cellular transformation. He made HPV16 and 18 available to the scientific community. Vaccines were ultimately developed that provide =95 % protection from infection by the high risk HPV16 and 18 types. The vaccines may also reduce the need for surgery and the global burden of cervical cancer.

Discovery of HIV

Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.

Importance of the HIV discovery

Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood

products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.

Identification of virus-host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.

HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people.

Harald zur Hausen, born 1936 in Germany, German citizen, MD at University of Düsseldorf, Germany. Professor emeritus and former Chairman and Scientific Director, German Cancer Research Centre, Heidelberg, Germany.

Françoise Barré-Sinoussi, born 1947 in France, French citizen, PhD in virology, Institut Pasteur, Garches, France. Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, Paris, France.

Luc Montagnier, born 1932 in France, French citizen, PhD in virology, University of Paris, Paris, France. Professor emeritus and Director, World Foundation for AIDS Research and Prevention, Paris, France.

Understanding the HIV virus

Ever since the HIV virus was discovered in 1983, a lot of research has been done around its genome. In the face of emerging and re-emerging viral threats, large-scale genome sequencing efforts are underway to monitor viral evolution in real-time. To fully appreciate the mechanisms of viral adaptation and evolution, and to also develop reagents and resources for a better molecular diagnosis of viral infections, there have been efforts at producing full-length viral genome sequences.

Research has shown that HIV drug resistance can be identified by genome sequencing. Hence it is important to study the influence of the changes in the HIV genome. At the National AIDS Research Institute (NARI) in Pune, scientists are just six months away from completing the sequencing of the HIV genome. And according to Director Dr R.S. Paranjape, initial trends show that the Indian virus is slower in its progression than the South African Sub type B and C. The Indian subtype C strain of HIV is different from the subtype C strain in China and South Africa, he explained.

NARI has been working on this project for two-and-a-half years and has sequenced 60 strains in the country. “What is the genetic make up of the virus? How has it evolved? How can the evolution go further? These are the issues being looked at. A large number of samples from patients, stored away for years, is being analysed and we are looking at evolutionary trends,” says the director.

Dr Jayanta Bhattacharya, who is also working on the project, says genome sequencing basically means to read the genetic makeup of a given virus strain. The genetic sequence of HIV is obtained by amplification (through polymerase chain reaction) of the integrated provirus in peripheral blood mononuclear cells (PBMC) or from the HIV + plasma and subsequently reading the DNA sequences with the help of a genetic analyser.

HIV virus particle

If you were to look at a HIV virus particle under a microscope, it would look something like this:

The size of the particle is around 0.0001mm.

(For a more detailed simulation, see 3D HIV.)

There are two main parts, essentially: the inner core (the "pill-shaped" section in the diagram), and the viral membrane. Let's look at these in a little more detail:

The viral membrane encloses the particle, and has about nine or ten gp160 spikes embedded in it which are involved in binding and membrane fusion when the virus particle attaches to a cell.

The inner core is the "payload" of the virus, containing the viral RNA and some enzymes (reverse transcriptase, protease, integrase).