Day 3 at CROI

Seattle sits on the extreme northwest of the USA and borders Canada to the north. It has a very busy port which is one of the busiest in the country and was named after a local Native American chief of the Duwamish and Squamish tribes. This explains its distinctly un-English name, same as other states whose names were derived from Native American names such as Minnesota, Saskatchewan, Mississippi and Nebraska. This happens to be the headquarters for Boeing, the airline manufacturer.

Yesterday, the opening plenary session featured Dorothy Mbori-Ngacha from UNICEF who talked about the elimination of mother-to-child transmission of HIV. She pointed out that 92% of all vertical infections are happening in sub-Saharan Africa whilst the same phenomenon has almost been eradicated in high-income countries. The global consensus to eliminate infection in children and improve the health of mothers and children in resource-poor settings is fraught with many challenges that need to be addressed before it can become reality. Some of these include recruitment and retention of pregnant women into care. Data from two studies in South Africa and Zambia presented at the conference revealed an unacceptably high rate of loss to follow-up by pregnant women. There is a dire shortage of skilled birth attendants in many resource-poor settings, and there is also a palpable lack of treatment of women for their own health. There are a number of challenges in implementing the WHO 2010 guidelines on PMTCT and infant feeding, and all these challenges have to be addressed before the set goal of 90% PMTCT coverage can be reached.

Session 34 looked at the risk of HIV-exposed and infected infants and children.

Some of the conclusions that came from the presentations:

· Patterns of growth, mortality and morbidity are higher in children exposed to HIV but uninfected than their unexposed counterparts. This group of children is most vulnerable when their mother’s CD4 count is high, or when she dies. HIV exposure in children is associated with immune abnormalities, and these might be caused by a number of factors, including exposure to maternal HIV, exposure to HAART, exposure to other maternal complications and lack of breastfeeding (for infants on exclusive formula). Prevention of HIV infection in adults is key to preventing such complications.

· During the early years of the pandemic, the only testing available for infants was the ELISA assay, and this was only done at 18 months of birth . In 2004, the WHO then settled for a DNA PCR (polymerase chain-reaction) test that could be done at 6 weeks of birth. A number or problems still persisted with laboratories having different capacities; some infants were not tested, poor turn-around of results and initiation of positive infants on HAART. Newer laboratory-based HIV testing technologies and point-of-care devices are now in the offing, and these can perform tests earlier than the current 6-week threshold.

· A controversial presentation looked at the controversies and consequences of initiating HIV+ infants. Managing HIV infection is more challenging due to high viral loads, limited drug options, poor palatability of medicines and reliance on caregivers. As an answer to the unsustainability of life-long ART, Andrew Prendergrast proposed treatment interruptions, and this suggestion met with strong negative reactions from the audience.

Other sessions were as follows:

1. Neurological issues in HIV infection

2. Treatment in Resource-Limited settings: Impact and Challenges

3. Advances in Vaccines and Immune-Based Therapies

4. Drug resistance

5. Aging and Neurocognitive Impairment

6. Elite Controllers (also known as long-term non-progressors)

7. Viral Latency and Reservoirs

8. Metabolic and Cardiovascular Complications

My apologies for the "censored" view on yesterday's posting.

The 19^th edition of CROI is being held at the Washington State Convention Center in the heart of downtown Seattle. This is an imposing structure that renders the 4000+ crowd of scientists, clinical investigators, health researchers and community representatives pretty insignificant. I have been trying to find out what Seattle is famous for, and should have the answer in my next mail. For the meantime, it suffices to say that Jimi Hendrix was born here.

Today’s plenary commenced with a talk from Wafaa El-Sadr on ART for Prevention. Whilst the preliminary results from HPTN 052 confirmed the long-held view that ART had a dual benefit in preventing HIV progression in the host and infection, a number of issues still need to be tackled. For instance, are the results from 052 relevant to other populations beyond the stable HIV-discordant couples studied? What would be the impact of expansion of ART for prevention in discordant couples on the trajectory of the epidemic? What are the resource implications for scale-up of ART for prevention efforts and how does ART for prevention fit within the broader HIV prevention strategy? After the hubbub over the results has died down, the real challenge of translating the successes into reality begin.

Session 7 was on critical treatment issues in women and children. Two back-to-back presentations were on the relationship between use of hormonal contraception and progression in HIV-1. The recently-issues WHO guidelines on the subject has given little reassurance to women living with HIV on the safety of using hormonal contraception, hence the two presentations were of critical importance. Sandra McCoy and her group worked on a study that evaluated the risk of HIV acquisition among women using oral contraceptive pills and injectable hormonal contraception in South Africa and Zimbabwe. Data was analyzed from 4913 sexually active women aged 18 to 49 years participating in the MIRA study (Methods for Improving Reproductive Health in Africa). The study concluded that injectable use was associated with a slightly increased risk of HIV infection compared with non-hormonal contraception, and recommended the use of dual protection with condoms. Renee Heffron, on the other hand, presented data from a prospective study involving 2236 HIV+ women in east and southern Africa, and the conclusion was that hormonal contraception did not accelerate and was instead associated with a reduced risk of HIV-1 disease progression.

Studies that looked at loss to follow-up (LTFU) among HIV+ women show a high level of LTFU by pregnant women than non-pregnant women (19% vs 11% in 5 South African cohorts).

Interestingly, study in Tororo, Uganda, among children concluded that an ART regimen containing ritonavir-boosted lopinavir significantly reduced the risk of malaria than those receiving an NNRTI-based regimen b y 41%. This finding could be used to advocate for the use of PIs as first line for children and other populations in malaria-endemic settings.

The conference continues today with an opening plenary session by Dorothy Mbori-Ngacha on elimination of MTCT (mother-to-child transmission) of HIV.

The Conference on Retroviruses and Opportunistic Infections (CROI) opens today, Monday the 5^th March 2012 in Seattle, Washington, USA. This global premier scientific HIV research meeting provides a forum for basic scientists, clinical investigators and global health researchers to present, discuss, and critique their investigations into the epidemiology and biology of human retroviruses and the diseases they produce with the ultimate goal of translating laboratory and clinical research into progress against the AIDS epidemic.

The 2012 edition of CROI comes at a momentous time when the buzz has turned from rolling out universal antiretroviral therapy to finding the all-important cure that will spell the end of AIDS. The earth-shattering results of HPTN 052, reporting a 96% HIV prevention efficacy of early ART, brought the world a step closer to ending HIV through a massive HIV treatment scale-up that will make HIV+ people less infectious. Identifying serodiscordant couples and immediately commencing the positive partner on ART will virtually eliminate the possibility of infection to the negative partner.

The case of the Berlin patient, Timothy Ray Brown, the only man scientifically proven to have been cured of HIV through a bone-marrow transplant, opened discussions on the possibility of a functional cure. Brown underwent a radical procedure that may not be available to many people but the development got researchers talking about the possibility of engineering human cells to eliminate the CCR5 co-receptor which will result in the HI virus finding less traction in fusing with the human cells.

The drive towards a cure for HIV has gathered momentum and we wait with bated breath to find out whether researchers have made any headway in finding a method for eliminating the viral reservoirs or succeeded in genetically engineering human cells to prevent the virus gaining a foothold on the CD4 cell. At any rate, it is refreshing to note that the cure agenda features prominently on the program, a far cry from previous conferences where talk revolved around optimal ART combinations and the wonders of new ARV drugs.

The end of AIDS cannot be far off. With the same intensity that they have worked to produce safer and more efficacious HIV medicines, our researchers have turned their efforts in finding that therapy that will completely eliminate the virus from the human body. It might seem an impossible task given the havoc that has been wreaked by this small virus over the last three decades. But the job must be executed with the thoroughness and dedication of an archaeologist who assiduously seeks for that small shard, a mere sliver, a link to an ancient civilisation that unlocks the mysteries of the past and defines our being.

From Seattle, I will be sending daily updates of the conference. Note that there is a 10-hour difference between Seattle and Central Africa time, so “today” here can be “tomorrow” in Africa.