Baby with HIV “cured” – what does this mean for Africa?

Are we a step closer to finding a cure? In 2008, the first person Timothy Ray Brown known as “The Berlin Patient” was the first person reportedly “cured” of HIV. Six years on since having a series of complex medical procedures which included chemotherapy and a bone marrow transplant, he has no detectable levels of HIV.  Last week  the media was in a frenzy over a second possibly cured patient – this time a two year old child, dubbed the Mississippi baby.  The infant, now two and half years old needs no antiretroviral drugs.

The baby tested positive for the virus at birth. She became infected because the mother was not tested in early pregnancy and was not given antiretroviral treatment to prevent mother to child transmission (PMTCT).

By the time the doctors realised that the mother had HIV, it was too late for the normal PMTCT protocol so instead as soon as the baby was born, 30 hours after birth, she was given the full three antiretroviral drug combination as opposed to the single dose ARV drug normally given to babies. The baby continued treatment for 18 months then the baby and mother disappeared – which is referred as “lost to follow up”. However when the infant returned six months later, even though she had not been on treatment for six months,  when tested the infant was found to have an undetectable viral load.

Scientists refer to this as a “functional cure”- when people test negative for the virus but some of the virus has remained but is inactive. Normally babies treated with this drug complement stay on treatment but this mother never came back for more treatment so this unexpected event of the baby not continuing treatment is how the scientists derived their “functional cure”.

According to UNAIDS, there were 330 000 children newly infected with HIV in 2011.Every child born free of HIV a UNAIDS initiative reports only a third of infants in need of antiretroviral prophylaxis receive it.

Is this the big one? Do scientists have the cure? Unfortunately it is not as simple as that. What this “functional cure” does provide is exciting new areas for research. This one HIV-free baby may also be an exception to the rule. It is possible that this baby, for reasons unknown, may be different to other babies. More rigorous research is required before scientists can determine whether newborn babies can be treated in this way.  Furthermore this potential treatment may not work when HIV is discovered later, such as with adults.

What does this mean for Africa? Unfortunately with most new and improved treatments, developing countries are always the last ones to benefit. Odd, when they are places most in need. But do we really need a cure for babies with HIV if they are already effective methods of preventing transmission from mothers to children?

Dr. Mary Guinan writes in CNN

But there was another great advance against the HIV virus that did not make big headlines. A simple treatment with anti-retroviral drugs can prevent babies from being infected by their HIV positive mothers in the first place. Of course, a patient cure is much more visible than an infection prevented. Maybe that is why we celebrate cure in a way that we do not celebrate prevention”

But she also ends well by saying

…..let us celebrate each success. Each one gives hope that we will eventually conquer one of the most formidable of viruses.

 

The most popular question about HIV

One of my other passions is writing an HIV and AIDS column in the Malawi Nation Newspaper. Readers are welcome to, in fact they are strongly encouraged to, email me their weird and wonderful questions and encouraging or scathing comments.

I  dug into my email archives to find out what is the most popular question people asked….If you guessed “Can vitamin supplements help fight HIV?” – guess again. If you guessed “How long can I live with HIV?” not that one either…the question I got asked most often…would you believe is…drum roll please….is about cuts and open sores. Here are some of the questions that readers have asked:

“If don’t have any cuts on my penis – I checked very carefully but I slept with a girl who might have HIV, am I safe?”

“ So if a chick alibe ma (does not have) sores and I don’t have any, is there any way for HIV to infect me?”

“If I masturbate someone else can I get HIV? Should I be wearing gloves?”

Note the question usually comes from guys.

And here ladies and gentlemen is the response:

People are often misled by the notion that during sexual intercourse the only way to become infected is through the open cuts and sores. This is only partly true.

HIV is spread during vaginal sex when HIV-infected semen, vaginal fluid, or menstrual blood comes into contact with the mucous membranes of the vagina or penis.

The Department of Health New York, US sums it best

In general, since there is more mucous membrane area in the vagina, and a greater possibility of small cuts in the vagina, women are more likely than men to get infected with HIV through unprotected vaginal sex. Teenagers and women entering menopause are at especially high risk for getting HIV (and other sexually transmitted diseases) because the tissue lining of the vagina is more fragile at these ages. Cuts or sores on the penis or vagina raise the risk of HIV infection during vaginal sex for both men and women. The presence of sexually transmitted infections also increase the risk of HIV transmission.

Cuts present on or in genitals can be invisible to the naked eye. HIV can NOT cross healthy unbroken skin but it can enter through an open cut or sore, or through contact with the mucous membranes. Transmission risk is very high when HIV comes in contact with the more porous mucous membranes in the genitals (vagina and penis), the anus (the bum), and the rectum which are inefficient barriers to HIV. Transmission is also possible through oral sex because body fluids can enter the bloodstream through cuts in the mouth. Likewise transmission is possible during masturbation or “fingering” if cuts are present.

Nobody has magnifying glasses for eyes so you wouldn’t be able to see the smallest of cuts, you are much much much better off using a condom to reduce the risk of getting HIV during vaginal sex.

JustMilk, the nipple shield for preventing mother to child transmission of HIV

(adapted from  article in the Weekend Nation, Malawi – Lifting the Lid on HIV and AIDS 2nd April 2011)

Modifying technology might be the solution to curbing the spread of HIV and AIDS.  JustMilk nipple shield is a low cost, modified nipple shield that releases antiviral compounds to reduce HIV transmission from mother to baby during breastfeeding.

The JustMilk nipple shield is the work of scientists at the University of Cambridge with collaborators from the United States. A nipple shield is a nipple shaped flexible plastic covering worn over the nipple during breastfeeding. Nipple shields are used in various situations: to help young babies who have problems latching onto the breast, for women with irregular nipples that point inside the breast, for mothers with cracked nipples or for babies who are used to the plastic bottle teat.

Research shows that approximately 200,0000 babies contract HIV from breastfeeding each year in sub-Saharan Africa. HIV positive mothers often have no alternative than to breast feed as formula feeding can be very risky. Formula feeding in low resource settings is either not provided adequately or regularly resulting in malnutrition in the baby and is often made with unsafe drinking water which causes diarrhoea.

Image courtesy of JustMilk (http://justmilk.org/)

The nipple shield is meant to be a low cost option for HIV-positive mothers. Think of the nipple shield as a breast milk filter. Inside the filter are antiviral agents that reduce the likelihood of HIV transmission by either reducing the amount of virus in the milk or providing partial protection within the infant against infection. The study is also investigating the delivery of medications and nutritional supplements through the modified nipple shield.

Their approach involves modifying an existing commercial nipple shield by adding replaceable inserts (e.g. cotton-wool) that contain antiviral agents that inactivate the HIV without harming the baby. This allows the mother to directly feed the baby rather than having to collect and heat the milk (currently the only established method of treating HIV infected breast milk), which can result in social stigma. Anti-HIV agents have been identified that do not have a detrimental impact on the nutritional content of milk, and initial research and laboratory tests performed by the team indicate this idea may be feasible.

HIV info round up for Malawi

[taken from Lifting the Lid on AIDS published in the Nation, Dec 2010]

All in all, I think this year has been a good one for Malawi. The government is pushing forward with some of the new WHO recommendations e.g. to start ARVs at higher CD4 counts (350) as well as new drug regimens. That means doubling the number of people on ARVs and putting them on more expensive drugs, a very costly exercise for a poor country.

In Malawi, fewer people are dying from AIDS, more people are getting tested and the prevalence of HIV has dropped but that’s no cause for celebration…there is still a lot more to be done. Use of condoms still remain low, circumcision is yet to become a national policy, obstacles remain for full mandatory implementation of the prevention of mother to child transmission, and stigma and discrimination continue to be a cause for concern for people living with HIV.

Other highlights of this year, Mary Shawa, Secretary for Nutrition, HIV and AIDS in the Office of the President and Cabinet, caused a bit of a stir when she said too much maize affects HIV transmission but more research on that study is needed. In March, prostitutes demonstrated in anger over an HIV criminalization bill that will do more harm than good. Aunty Tiwo and Steve Monjeza, thank you for putting in the spotlight same sex couples, something that we, Malawians, must stop blasphemizing about and find a modicum of acceptance for this lifestyle.

Looking into the future for 2011…..is there any hope for a cure….significant progress is being made with a vaccine but it will be several years before something viable will be available on the market. The microbicides trials are looking hopeful. But..more research and more funding is needed but while we wait, let us act on the knowledge we have…protect yourself, get tested early, and those on ARVs take your treatment regularly!

To snip or not to snip….that is the circumcision question

28th February, 2010

The arena of HIV and AIDS and male circumcision (MC) is swarming with political, cultural, medical and religious motives but I would like to take a step back and put across to you, simply, what the science says. I have a strong opinion on the matter of MC but I will try my best to give you an unbiased, unflinching review of the science. Male circumcision is the removal of some or all of the foreskin from the penis. According to the WHO, three out of every ten men in the world are circumcised, and close to 70% of those circumcised are Muslim.  In Malawi, 21% of males are circumcised. Without delving in too much detail, there are global controversial debates on circumcision – one camp argues that it affects penile function, sexual pleasure, and is against human rights while the other suggests that it has health benefits and causes no complication if performed by an experienced physician. However, my interest and yours in reading this article – is the fact that it has been shown consistently and significantly (and by significantly I mean by 60%!) that  male circumcision reduces the risk of HIV transmission during penile-vaginal sex (to be clear, it reduces transmission from women to men) but…as there is always a but… the cautionary note is that it only provides MINIMAL protection and by no means can and will NOT replace other prevention methods.

Several studies have been conducted to investigate the relationship between circumcision and HIV infection but three particular studies in Uganda, South Africa and Kenya led the WHO/UNAIDS  in 2007 to recommend male circumcision as an HIV prevention tool.  The trials in these three countries were stopped early because it was found that those in the circumcised group had a lower rate of HIV infection  than the uncircumcised group. The results showed that MC reduced vaginal-to-penile transmission of HIV by 60%, 53%, and 51%, respectively. To date however, there is insufficient evidence to show protection of male to female transmission and men who engage in anal sex with a female partner.

As most men, about 70%,have acquired HIV through vaginal intercourse it is important to understand the biological factors that are involved in reducing HIV transmission in circumcised men.  Studies are still ongoing but it is generally recognised that the inside of the foreskin is rich in cells that are susceptible to HIV infection – this is important because the inside of the foreskin is pulled back during sexual intercourse and the whole inner surface of the foreskin is exposed to vaginal secretions, providing a large area where HIV transmission could take place. It also believed that the skin, frenulum,  that connects the foreskin to the penis is susceptible to trauma during intercourse. The frenulum is also the common place where  lesions from sexually transmitted infections (STIs) occur and since people who have STIs like syphilis or gonorrhoea are two to five times more likely to become infected with HIV, MC may be even more protective.

So in light of these glaring findings what is Malawi doing?  I was able to find a recent UNAIDS report (December 2009) that gave country updates on scaling up of MC in Southern Africa –the report basically shows that Malawi has done nothing on this issue besides forming a committee. No focal person has been indentified, no communication strategy developed with a note that more lobbying and advocacy is needed – need I remind you that it has been two years since the WHO recommendation on MC. Apparently government is confounded by the results of a survey that found high prevalence of HIV in areas such as Balaka where MC is practiced. One study  that may clarify this anomaly is being done by the College of Medicine, University of Malawi. The study’s main purpose is to investigate discordant couples (when one partner is HIV infected and the other is not) but will also look at “the effect of male circumcision in different geographic settings and by ARV treatment strategies”. We eagerly await the results when the study is completed in 2011!

Meanwhile other countries like Swaziland  have embraced the WHO recommendation to the point that the Swazi Ministry of Health and Human Services opened a facility in October 2009 committed to making Swaziland the first country in the world where 80 percent of males in the age group most vulnerable to HIV infection (15 to 29 years) would be circumcised by 2014. The procedure at Litsemba Letfu (SiSwati for Our Hope) Male Clinic is free. Before the procedure men are counselled on the risks and benefits of MC and invited to test for HIV. Men are also invited to bring their partners so that they can understand the procedure. Counsellors emphasise that MC only reduces a man’s chances of contracting HIV by about 60 percent and should be combined with other prevention strategies.

A USAID report is advocating for MC in Malawi, the report describes that  if MC was scaled up to 80% of the male adult population by 2015 in Malawi, 265,000 deaths would be prevented between 2009 and 2025 and that MC can save by the year 2025, $1.2 billion. Another study looked at acceptability of MC and found that acceptance of MC would vary by region with acceptability lowest in the North where little is known of this practice but many parents and young men across the country would use the services if it were safe, affordable and confidential. So really what are we waiting for?

This article was first published in the The Nation, Malawi – column on Lifting the Lid on HIV and AIDS, Feb 27th 2010

The Malawian context of the new WHO recommendations for HIV treatment

The WHO on the eve of World Aids Day (30th November) issued new recommendations for treatment, prevention and infant feeding in the context of HIV,  based on the latest scientific evidence.  Highlights of the new recommendations include starting antiretroviral therapy (ART) earlier in adults and adolescents, delivery and use of better-tolerated and more conveniently administered antiretroviral drugs (ARVs), and longer use of ARVs to lower the risk for mother-to-child HIV transmission.

In the last five years close to 50 scientific articles have published research on Malawi, recommending similar actions. The Ministry of Health in Malawi has been slow to act, ignoring these findings and awaiting guidance from the WHO. This is ironic because some of the WHO advisers are the very same said local researchers but government  prefers WHO to rubberstamp new guidelines.  I am certain that our local research has influenced the revised WHO policy, however  I am not sure to what extent, but none the less I would like to highlight some papers that were published and discuss the implications of these recommendations in reference to Malawi.

Earlier start to ARVs and clinical laboratory tests

The WHO advocates starting ART when CD4 cells, which are defense cells of the immune system, fall below 350 cells per millilitre. The previous recommendation was 200 cells per millilitre but research has shown that an early start can reduce death rates.  A paper published last year  found that death rates were high in those who started ART at CD4 counts of less than 200. However,  in some cases  in the absence of diagnostic equipment, WHO clinical staging has been used. This system uses patient’s clinical symptoms to guide decision making but often fails to diagnose those eligible to start ART.

In accordance with the change in the CD4 level threshold, WHO is also encouraging increased access to laboratory tests that can not only determine CD4 levels but also viral load, the amount of HIV in the blood.

Breast feeding and mother to child transmission

WHO is recommending, for the first time I must add,  that HIV-positive mothers take ARVs during the entire course of breastfeeding to prevent disease transmission.  Several seminal papers have been published by researchers at Johns Hopkins in Blantyre on mother to child transmission, which have called for extended prophylaxis for infants.  The argument in the past has been  – to reduce mother to child transmission,  mothers should not breastfeed, but  in resource poor settings, mothers  often cannot afford to give their baby formula, plus there is  the added problem of providing formula with safe drinking water.  The new recommendations also call for HIV pregnant mothers to start ARVs at 14 weeks instead of the previous 28 weeks.

ARV drugs

The WHO is also urging for the replacement of stavudine, or d4T — a first-line antiretroviral with tenofovir or zidovudine. Stavudine is readily available and cheap in developing countries but has been known to produce irreversible side effects.

The new recommendations will lead to more people needing treatment, said the WHO, but they say: “The associated costs of earlier treatment may be offset by decreased hospital costs, increased productivity due to fewer sick days, fewer children orphaned by AIDS and a drop in HIV infections.” But I ask what could this mean for Malawi?

Some reports estimate that the new recommendations would mean 2.5 to 3 times as many people will be eligible for treatment. In 2005, only 14,300 people were on treatment, in 2009 250,00, this is a commendable achievement by Malawi’s National AIDS Council (NAC) although this still falls short of the number in need of treatment which was estimated as 340,000 by UNAIDS in 2007. Therefore NAC has to double their efforts in order to provide universal access to the “newly” eligible .

Access to laboratory testing facilities must be improved so that people in remote areas should be able to conveniently and regularly have CD4 count and viral load tests  and even in the absence of these tests should not be denied treatment.  This will require machines and trained staff in places as far as Nsanje and Chitipa.  A paper by van Oosterhout has discussed how viral loads can also determine patients whose treatment is not working.

The current recommended first-line treatment for ARVs in Malawi is a combination of three drugs that include stavudine, with the average cost of this combination therapy pegged at  US$ 15 per person per year (2005) . Replacing this drug will be expensive but if the President follows through with his commitment,  we could be manufacturing our own ARVs which would drastically reduce the cost.  The drugs recommended to replace stavudine , tenofovir or zidovudine, although more expensive will offset the cost of reduced toxicity management in hospital.

All the recommendations urgently require money, but with so much criticism of late in funding AIDS programs, where will the money come from?

Making sense of HIV prevalence data

30th November, 2009

Marching on with my bold ambition to engage people with science; the upcoming World AIDS day (1st December in case you did not know),and spurred by the book I am reading, Bad Science by Ben Goldacre (which is a revelation on the misrepresentation of science in the media) – I have decided to focus this blog on AIDS research in Malawi. A quick and dirty search on Medline – the largest international biomedical journal database, reveals that so far in 2009, 35 scientific papers have been published that report on AIDS in Malawi. After a close examination of these articles, I excluded three that are not AIDS specific (one was on visually impaired children and the other two on human resource). Before I proceed I would like to caution that not all published studies are indexed in Medline and searches of other databases e.g. Africa Journals Online might reveal more papers. However saying that, a journal’s inclusion in Medline is a mark of quality. I will discuss articles that were of particular interest because they discussed a sensitive issue, had far reaching implications for policy and practice or highlighted an important public health crisis.

One article that caught my eye is titled Refusal bias in HIV prevalence estimates from nationally representative seroprevalence surveys by Reniers and Jeffrey published in the journal, AIDS1. This article discusses the relationship between prior knowledge of one’s HIV status and the likelihood to refuse an HIV test and how this can bias HIV prevalence estimates. This article got me thinking about HIV prevalence, a very common statistic that is frequently cited by activists, policy makers, scientists and all manner of institutions.

HIV prevalence as defined by the WHO is the percent of people with HIV infection among all people aged 15-49 years. This statistic is very important for purposes of advocacy, programme planning and evaluation. e.g. adequate stocking of ARVs in clinics, monitoring the trend and the impact of programs. The WHO website provides some insight on the rationale for its use and methods for its estimation. I wont bore you with the calculations but you should know that in the 1990s this figure was generated from surveillance systems that used data on pregnant women who attended preselected antenatal clinics (ANC). The major assumption was that prevalence amongst pregnant women was a close approximation of the prevalence in the adult population of men and women between the ages of 15-49. Now you may well ask why specifically the age range 15-49? Unfortunately, I was only able to get a vague answer from a UNAIDS document that states this age range covers people in their most sexually active years, with people most likely to become HIV infected in these years. Depending on who is reporting the prevalence in Malawi it can range from 15% to 12% but the official figures according to various sources are as follows

–         UNAIDS, WHO. 2007 AIDS epidemic update reports prevalence in Malawi in 2004 for population based survey at 12.7% . Whilst for the years 2001, 2003, and 2005 is 15%, 14.2% and 14.1% respectively.

–         The 2004 Malawi Demographic Health Survey (MDHS) reports an observed prevalence of 11.8% and a nonresponse-adjusted estimate of 12.7%. Nonresponse adjustment refers to adjusting for persons who were not tested for reasons such as they either refused or were not at home when the health worker came for the test.  (The MDHS project  is a goldmine of information gathering data on a range of health and demographic indicators like fertility, childhood mortality levels, awareness and use of family planning methods, and knowledge and behaviours related to HIV/AIDS and other sexually transmitted infections at the regional and national level. They do not survey everyone but use fancy statistics to sample a select Malawian population which is extrapolated as representative of the whole population. They conduct interviews with subjects and in the case of HIV do blood tests.)

–         I did try and access figures from the National AIDS Commission but NAC’s website www.aidsmalawi.org.mw was not responding (!*^!%!).

If you look at the figures you may notice (with horror) that in 2003 the figure was 14.2% and then 2004 12.7% and then went up in 2005 to 14.1% but it is incorrect to analyse it in this way because the the source of the data varies and is not comparable. The data for 2004 was sourced through population based surveys – the MDHS – which actual tested a sample of the population while the other figures are based on ANC data. Both methods have their pros and cons. It is now recognized that the use of prevalence estimates based on ANC typically overestimate true prevalence because the women who attend ANC are not representative of all pregnant women e.g. women in rural and remote areas do not attend ANC so therefore would be underrepresented in such a sample. Additionally women with HIV associated infertility are not captured; and men and non-pregnant women are not included. The UNAIDS Reference Group on Estimation, Modelling and Projections responsible for developing methods for calculating prevalence have now developed schemes to correct and improve ANC data.  There is an interesting comment on the WHO website “The main indicator proposed for monitoring progress towards achieving the international goals is HIV prevalence among young people aged 15-24 years which is a better proxy for monitoring HIV incidence than prevalence among ages 15-49 years.”

Population-based surveys like MDHS are expensive and logistically difficult to carry out and are therefore not conducted every year. But taken together, both sources complement each other and provide a clear picture of overall trends, geographical distribution of HIV, and information on high risk groups.

Going back to the study by Reniers and Jeffreys,   they revise the 2004 HIV prevalence estimate to 13.3% (in one place it is quoted as 13.2% which is wrong!) and suggest that “our estimates are conservative”. What the authors are putting forward is that people who know their HIV positive status are more 4.62 times more likely to refuse to participate in a health survey such as the MDHS. This refusal can bias the final prevalence estimate, bearing this in mind they have revised this figure to a prevalence of 13.3% for Malawi in 2004. So what does this mean in actual numbers, we would need know to the actual population of people aged 15-49 in 2004 but unfortunately censuses (yes censusus is a plural for census) have only been done in 2008 and 1998 so let us for example say they were 6 million aged 15-49 in 2004 (assumed from  CIA World Factbook Malawi 2004 )  for the MDHS  figure of 12.7% means  762,000 HIV infected people – and for the authors 13.3% is 798,000 HIV infected people,  a difference of 36,000 people. And if you remember that these figures are important for planning and monitoring purposes then 36,000 can be significant. ( I am not a statistician so I am unable to say whether this is statistically significant).

I think I have rambled for far too long on statistics and science but I hope now you have a better understanding of prevalence, how it is derived, and how figures may vary depending on population based survey data or ANC data. Finally and importantly remember that a prevalence of 10%  means that 1 in ten people between the age 15-49 are infected, not every tenth person!

I will as promised in the next blog look at some other scientific papers on AIDS research in Malawi.

Don’t forget to buy your red ribbon, support an AIDS charity, and say a prayer for those living and affected by HIV and AIDS.

References

1. Reniers G, Eaton J (2009) . Refusal bias in HIV prevalence estimates from nationally representative seroprevalence surveys. AIDS.13;23(5):621-9.