Cure for HIV: A prize to keep our eyes on

Cure for HIV: A prize to keep our eyes on

The call for a cure was launched in February 2011 by the president-elect of the International AIDS society and Nobel Prize winner Françoise Barré-Sinoussi. The article by Lewin et al (2011) provides an excellent overview of possible promising strategies for cure using an ‘infectious disease model’ (sterilising cure model), in which HIV and all HIV-infected cells would be eliminated, or a ‘cancer model’ (functional cure model), in which there would be long-term health in the absence of treatment accompanied perhaps by low levels of HIV in the blood.

The three challenges to finding such a cure are:  (i) viral latency in resting CD4 cells (HIV lying low with its genes turned off, unaffected by antiretroviral drugs or host immune responses), (ii) residual viral
replication (with low amounts of HIV reseeding the blood stream), and (iii) reservoirs (hiding places such as the gastrointestinal tract, the brain, and the genital tract). Latently infected cells are rare (1 in 100,000 to 1 in a million) so using promising strategies such as the histone deactylase inhibitors used in cancer that could turn HIV genes on or cytokines that could activate latently infected cells to replicate so that antiretroviral therapy could take effect, may haveindiscriminate effects on uninfected cells since these therapies will no select for only infected cells. The potentials for side effect will therefore be a challenge. Gene therapy with zinc finger nuclease to reduce CCR5 expression and block HIV docking is another possibility and is currently being explored in some ongoing studies.

The famous ‘Berlin’ HIV-positive patient who was treated twice for acute myeloid lymphoma with a pre-transplantation conditioning regimen, including total body irradiation, followed by transplantation of stem cells from a special donor is a point in time study of the possibility of a HIV cure (Allers et al, 2011). This patient had to undergo bone marrow transplantation twice due to leukemia. That bone marrow stem cell donor was homozygous for the CCR5Δ32 deletion (i.e. both genes coded for this deletion), meaning that his or her HIV target cells did not allow HIV to complete docking after linking with the gp120 receptor. Donor-derived memory CD4 cells replaced the recipient’s cells reaching the normal range over a 2-year period and HIV has remained undetectable in gut tissue, brain, bone marrow mononuclear cells, and peripheral blood cells (residual viral replication sites). The patient remains susceptible to HIV infection
if he is exposed to CXCR4-tropic HIV. It is impossible to analyse every cell in living humans so proving viral eradication is impossible. However, given that HIV has not reappeared after 3 years without antiretroviral therapy, the authors conclude that a cure has been achieved. With stem cell transplantation carrying a mortality of up to 30%, this procedure is not practical but this story does give hope that one day we will find a cure for HIV.

While we wait and hope for a cure in our lifetime, universal access to antiretroviral treatment remains top priority and an agenda for all nations in view of the evidence to show that treatment could also serve as a prevention tool. These are early days to be talking about a cure. But community engagement in this basic/clinical science challenge is key—this is one prize we need to keep our eye on.

(Adapted from the edits of Cate Hankins – Scientific Adviser for UNAIDS and Editor for HIV This week – Issue 91)

References:
1. Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure
for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4.
2. Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E,
Schneider T. Evidence for the cure of HIV infection by CCR5Δ32/Δ32
stem cell transplantation. Blood. 2011 Mar 10;117(10):2791-9

 

The need to discuss a rectal microbicide agenda for Nigeria

The need to discuss a rectal microbicide agenda for Nigeria

I am in Ethiopia and I sat down through a 2 days session listening to data presentation about the HIV context and situation in Africa. Asusual, I was all out to hear and listen about what the data was saying

about Nigeria.

One key issue was the place and role of anal sex in driving the HIV epidemic in Nigeria. This can no longer be ignored. As per statistics, yes there are Statistics from Nigeria that shows that anal sex is
practiced by 12% of public secondary schools students (Bamidele et al, 2009). There was another presentation that showed that 12.1% of university students  and 15.2% in-school adolescents in Northern Nigeria practice anal sex.

What does this evidence mean? Anal sex is known to be the highest risk form of sexual transmission of HIV infection with approximately 14 (10 – 20) times higher risk of HIV transmission when compared to
penile-vagina sex. The probability of HIV infection transmission in penetrative anal sex is about 1.4% per sex act both in heterosexual and homosexual relationships.

There are evidence to show that about 10% of women and 14% of men in the general population practice anal sex with condom use being low during this sexual practice as a result of multiple erroneous believes including believes that anal sex is safer than vagina sex. Request for anal sex by clients of FSW is high (not a negligible proportion) with men paying higher to have anal sex with sex workers (male and female) for many reasons (more pleasurable, tighter, gets to ejaculate faster and for prevention of STIs, and it is cleaner as fewer people engage with this ‘hole’).

And you know what? For women, the risk is highest as they will always be the receptor in either vagina or anal sex. Maybe this be an unidentified driver of the HIV epidemic amongst females. Study do show
that many women engage in anal sex during pregnancy, menstruation, for pleasure and a whole host of other reasons. Yet evidence show that as receptors of sex (anal or vagina) their risk are increased.

What do we need to do? I personally think there is the need to discuss more openly about the risk of anal sex. Many times we discuss sex during our sex, sexuality and HIV education in a way that
unconsciously limit our verbal and non verbal communication about sex to vagina sex. Our discussion around sex must become broader to encourage public understanding of the multiple forms of sexual
practices (vagina, oral, anal) and the risk of HIV infection associated with all the forms of sex. I had personally been engaged in a public discuss with university students where a major player in the
HIV field actually noted in her discuss that anal sex was safe. Anal sex is associated with high risk and we need to get the public to understand this. Our family life education series need to identify
this and share this information in schools in view of the statistics that show that despite under-reporting, 12% -15% of adolescents practice anal sex.

Do we discourage anal sex? People have choices. We need to promote safe practices. Anal sex and howbeit all sexual practices need to be made safe (use dental dams for oral sex, condom for vagina sex, and condom + lubricants for anal sex and vagina sex with the vagina is dry). These are existing tools and are effective. We need to advocate for increased distribution and access to lubricants in the same spaces as condoms can be accessed. And for the future, there is the rectalmicrobicide.

What is rectal microbicide? It is a product currently being developed. When developed, it will be available as a lubricant, gel, douche or an enema that can be used by women and men to reduce the risk of HIV transmission during anal sex. It would be able to offer some level of protection from HIV infection even in the absence of a condom. It would also serve as a backup protection if a condom breaks or slips
off during anal intercourse. For more information, visit www.rectalmicrobicides.org

Some Nigerian researchers are very much interested in conducting rectal microbicide research. Lets support this process. Lets speak up for rectal microbicide in Nigeria. Lets discuss about this during our
World AIDS day activities as we ensure a AIDS free generation.