New HIV Prevention technology pipelines – ARV treatment of index partners

There is strong evidence to suggest that antiretroviral treatment
reduces HIV transmission by lowering viral load. Evidence from at
least one study show that current efforts to expand access to
treatment in sub-Saharan have probably resulted in a major reduction in HIV transmission. A three year study in Uganda of antiretroviral treatment coupled with intensive adherence support, behavioural counselling and partner testing led to an estimated 90% reduction in onward HIV transmission, CDC researchers calculated.

An ongoing study, is trying to determine if earlier treatment in
individuals with CD4 counts between 300 and 500 is more likely to
reduce HIV transmission in serodiscordant couples than treatment
initiated according to standard guidelines (the standard guideline
recommendation is that ARV treatment should start when the CD4 count is 200 or less). The study is recruiting in Brazil, India, Thailand, Malawi and Zimbabwe, and expected to report by 2013.

The world awaits the result of this study!

New HIV prevention technology pipelines – the story of PreP

Pre-exposure prophylaxis (PrEP) is the use of antiretrovirals prior
to exposure to HIV to prevent infection. PrEP is intended for use by
people who may be at frequent risk for HIV. This includes people who engage in high-risk behaviour groups such as sex workers, injecting drug users, and people who have unsafe sex with a multiple partners (or whose partners have multiple partners). Currently, no
antiretroviral is yet approved or in use as PrEP. Serodiscordant
couples (sexual stable relationships where a partner is infected
with HIV and the other is not) could also benefit from PreP use.

Much of the data on PrEP result from research conducted in monkeys.
In general though not clearly so, these studies have demonstrated
that PrEP can decrease the risk of infection to varying degree.
these studies have also used different models for testing, making
comparisons of results across studies difficult.

The only human data to date, from a Family Health International
study of tenofovir PrEP in which recruitment was abandoned at two
sites due to a controversy over post-trial care, show no serious
safety concerns during an average of nine months’ follow-up.

Four PrEP studies are ongoing and three others are planned for
rollout as of february 2008. The ongoing studies are:
• An efficacy study tenofovir among injection drug users in
Thailand, sponsored by the United States Centers for Disease Control and Prevention (CDC) – expected to report efficacy results in 2009.

• A safety study of tenofovir among men who have sex with men in the United States, also sponsored by the CDC – expected to report safety results 2009.

•An efficacy study of Truvada among heterosexuals in Botswana, also sponsored by the CDC – expected to report efficacy data in 2010.

• An efficacy study of Truvada among men who sex with men in Peru
and Ecuador sponsored by the NIH – expected results in 2010.
The risk of HIV transmission is influenced by a number of biological
and environmental factors, including stage of disease, number of
exposures, viral load in blood and semen, as well as the presence of
other sexually transmitted infections. In addition, studies have
shown that most transmission occurs during the acute stage of
infection or at the late stage of disease, when viral loads are
high. According to studies from serodiscordant couples conducted in
Africa, HIV-positive individuals in the acute stage of infection
were responsible for 43% of all HIV transmissions. Knowing this. HIV
control strategy must be multiprong with a wide range of use options
for all persons affected by epidemic.

New HIV Prevention Technologies – HIV Vaccines


The promise of an effective HIV vaccine has always been just over the horizon, but more than 20 years after the identification of HIV,
vaccines remain far from implementation.

The two large HIV vaccine studies till date have shown no protective
effect.The latest is the Merck’s trial which not only showed that the
tested vaccine could not prevent HIV infection but also highlighted
some other findings:

1) The trial participants who received the vaccine showed the highest
risk of HIV infection in individuals who had had adenovirus infection
in the past. Adenoviruses most commonly cause respiratory illness.
they could also cause various other illnesses such as infection of
the GIT, eyes and skin depending on the type. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia and bronchitis

2)the trial also showed that the trial participants who had signs of
adenovirus infection, and were uncircumcised were at four times
greater risk of HIV infection if they received the vaccine compared
to circumcised men who had the adenovirus infection and were in the
placebo group. A vaccine study is still ongoing in Thailand and should be concluded in June 2009. A phase IIb HIV vaccine study known as the PAVE 100 study is still being planned to begin in 2008. While we have dissapintment in the field, more studies are still needed in order to improve understanding of the strengths and limitations of various HIV vaccines designs.

For the future, vaccine approaches would focus more on basic research without precluding clinical research. Currently, investment in
vaccine research comes overwhelmingly from the public sector and
foundations. Only one private company (Merck) has invested more than $10 million annually in vaccine research. Companies cite the current scientific uncertainty and the lack of incentives for conducting
phase II studies and investigating process development as barriers to entry to the field

Prevention of Mother to Child Transmission (PMTCT)

Mother to child transmission remains a major means of HIV
transmission. HIv can be transmitted from the mother to the child
through 3 routes:

1. During pregnancy when the mother goes through trauma that may
cause a tear in the placenta and allow direct contact between the
mother and the child’s blood. This should not happen normally. This
route of transmission for HIV infection from mother to child is quite
low

2. At delivery. When delivery is not taken carefully and the child is
exposed to contact with the mother’s vaginal fluid which is infected
with the virus, or the mother’s blood.ideally, HIV infected pregant
mothers should be slated for caserean section so as to further reduce this possibility

3. After birth through breast milk. This is the most common route of
infection. The breastmilk contains HIV virus. the virus could infect
the child through the gut. the gut contains a lot of CD4 cells and
therefore HIV infection can easily occur in the gut when exposed to
the virus. Often times, HIV infected mothers are advised not to
breastfeed. When they opt too for a number of different reasons, they are advised to breastfeed exclusively (breastfeed the child strictly on breastmilk only) before weaning off the child. Exclusive
breastfeeding is however recommended where replacement infant feeding is not acceptable, feasible, affordable, sustainable and safe

The use of prophylactic Amtiretroviral regimen to reduce the rate of
HIV transmission from mother to child has improved over the past ten years. Current WHO guidelines recommend a short-course regimen ideally consisting of AZT for the mother from week 28 of pregnancy, single dose nevirapine at the onset of labour, and AZT/3TC for 7 days after delivery. The infant should also receive a single dose of nevirapine at delivery, and AZT/3TC for 7 days. Mothers with CD4 cell counts below 350 should be considered for antiretroviral therapy. Despite the proven effectiveness of ARV to reduce rate of Mother to child transmission of HIV infection, mirage of logistic problems prevent the effective use of this innovation include the ineffectiveness of health systems. Less complex regimens are recommended where the health system cannot deliver this level of care, but even the delivery of single-dose nevirapine – the least effective regimen – has posed significant problems for health systems in sub-Saharan Africa. Detailed analysis of programme delivery in Zambia, for example, has shown that only one in three women diagnosed HIV-positive actually took nevirapine at delivery. But then only 30% of woment actually take an HIV test!

No recent analysis of potential technological improvements to PMTCT
programs has been carried out . Ongoing studies are investigating the efficacy of HAART (a ARV treatment regimen consisting of at least 3 drugs) and the safety and efficacy of tenofovir (a type of ARV).

Interpreting the results of HIV prevention trials (2)

Clinical Trial Results Are Valuable. This is because:
1. They can tell us which products are not studying anymore

2. They can point to the kinds of changes that could be made to
improve other clinical trial design

3. They may yield beneficial information about behavioral and
cultural practices that affect HIV transmission and the results we
get from clinical trials; and

4. They provide valuable information about how prevention trials can
be better managed.
Understanding Clinical Trial Results:
Prior to a clinical trial, studies of the product to be tested are
done in the lab and in animals. Small size, medium size and large
size animals are used when testing the product. the right animal is
also used. For example, when testing microbicides, the rabbit
vaginal is used because this is the most sensitive vaginal and if it
does not harm the rabbit vaginal, it may not harm the human vagina.
Doing a microbicide animal study using a donkey may therefore be
wrong.

After animal studies, there are also other phases of studies:
1. Phase I which looks at the safety of the product or drug in very
few people

2. Phase II which looks at the safety of the drug and also tries to
test if the drug can do what it is meant to do in an ideal
condition. This is known as an ‘efficacy’ study

3. Phase III which looks at the safety of the drug and also tries to
see if the drug or product can do what it is meant to do under
normal conditions

Eg – Ampicillin is an antibiotics that went through animal, phase I,
II and III clinical trials. It was found to be able to treat similar
human infections in animals. It was found safe in phase I studies.
In phase II studies, It was shown to produce good results when taken
every 6 hours for 7 days. In phase III studies, it was shown that if
people miss the every 6 hours once in a while, or use it for less
than 7 days (for 3-5 days) it can still be effective. For this
reasons, the drug went throuh further development.
What is a successful clinical trial:
A clinical trial could end in any of the phases. A phase III trial
could be end because:

1. There is proof that the product can work to prevent HIV infection
e.g. male circumcision

2. That there is no proof that th drug is working e.g. carraguard

3. That the product or drug is causing harm eg making people very
sick or causing more HIV infectione.g. N9

4. When the results are not clear and there is no evidence that it
would be clearer with ontinued study e.g. SAVVY
An HIv prevention Clinical Trial would be considerd Successful if:

1. The research plan is conducted as stated in the study protocol.

2. The study is done using the right method

3. The trial provides further information to the HIV prevention field

4. Trial participants are informed and educated about HIV, the
purpose and outcome of the study.

5. The health of participants is protected

6. Trial is continuously monitored at defined intervals by the right
persons who know what they should be looking out for

7. Participants and the community are engaged with the research
process in an ethical, respectful and efficient manner.

8. The trial participants did not abscond from the trial and so at
least 85% of those that started the trial stayed till the end. This
reduces bias

9. The study results are communicated to participants, their
communities and other stakeholders.

10. A plan to ensure trial participants and or the study community
has access to study products in the case of a positive result.