Why Women are more susceptible to HIV/AIDS than men
written by lmunala , July 24, 2008

Women are more susceptible to HIV/AIDS from heterosexual sex due to the greater area of mucous membrane exposed during sex in women than in men. In Africa speficically, it's a combination of economic,social, cultural and as stated above biological factors.

...
written by snkariuki , July 24, 2008

Thus the finding that DARC influences the quantity of the chemokine CCR5 ought to be related to disease progression. But questions remain unanswered. How great is the influence of DARC on chemokine CCR5 production? Is the pathway of DARC induction of CCR5 wholly dependent on the DARC gene?

He, Weiss, Ahuja et al. postulate that DARC regulates the biological effects of chemokines in three ways – either through scavenging, retention, or transportation. DARC hence plays a key role in the homeostasis of chemokines (including CCR5). They add that the ultimate impact of DARC on HIV-AIDS pathogenesis is a complex interplay between levels of DARC, circulating chemokines and circulating virions.

This trans-infection model of HIV is certainly interesting, where HIV binds red blood cells via DARC, and subsequently binds CD4 T cells-the target cells for HIV. In their proposed model, DARC ve subjects who likely have a higher level of circulating and red blood cell-bound CCR5 would be less prone to initial viral infection than DARC -ve subjects, since CCR5 acts as a shield in this trans-infection of HIV from red blood cells to CD4 target cells. Also, the higher plasma levels of CCR5 in DARC ve subjects might convey a protective effect against transmission.

In terms of the paradoxical difference in the rate of disease progression, they say that once this initial infection has occurred, the chemokine driven proinflammotory state in DARC ve subjects may far outweigh the HIV suppressive effects of high CCL5 levels, because DARC binds more proinflammatory cytokines, including those that increase viral replication, e.g. CCL2, than HIV suppressive chemokines. Also, since subsequent HIV infection (after initial exposure of a host to a small viral inoculum) is characterised by a huge viral load in the plasma, there may be improved virus and target-cell interactions at this stage. Hence there’s a greater probability of HIV displacing DARC-bound chemokines and in turn this DARC bound HIV making contact with CD4 target cells. Hence the presence of DARC may improve the efficacy of infection in DARC ve subjects. Since DARC -ve subjects may have a smaller reservoir of HIV-loaded red blood cells, and a reduced inflammatory state, disease progression rates may be slower. More details can be found in the discussion section of the paper.
http://www.cellhostandmicrobe....280800190X

This paper certainly provides interesting preliminary findings of one of the genes that might be responsible for HIV susceptibility in African populations. More work certainly needs to be done to test the strength of this model. There might also be other genetic and cellular factors at play. I’m sure this paper will pave the way for more comprehensive and conclusive findings in the future, as to the key factors that make people from different ethnic backgrounds more or less susceptible to viral infections and other diseases.

...
written by snkariuki , July 24, 2008

DARC ve (DARC positive subjects)
DARC -ve (DARC negative subjects)
Plus sign isn't visible...so hope this is clearer.

...
written by Stephen Wanyama , July 25, 2008

Madaktari, but is there an explanation that covers everyone? For example, the Gusii districts have a very high malaria prevalence, but very low HIV, remarkably low actually. Anyone would tell you that the North Eastern province is malnutrition central, but there is very little HIV there. The sub-Saharan explanation also seems faulty to me, it is especially in Southern Africa that we find high rates. Why has Zimbabwe in spite of all its troubles managed to check the spread of HIV so well? Questions, questions.

by ethnicity
written by Stephen Wanyama , July 25, 2008

Source here, Imagine on Scribd Page 23

...
written by Stephen Wanyama , July 25, 2008

Umm, transpose the women and the men column titles. The figures are still pretty startling in their difference, I find that an Africa-wide explanation is likely nonsense. What say the doctors?

...
written by snkariuki , July 29, 2008

True, there isn't a blanket explanation for this, especially if we're talking about a genetic causality, since Africans are diverse (indeed we're all different genetically). It would be interesting to see a study done using an African cohort to test this model (even just a Kenyan population, with its diverse ethnicities would make for an interesting study). For this particular gene though, if indeed all Africans have this same DARC negative genotype, it might be difficult to do a proper statistical comparison in order to really test the impact of this DARC gene on HIV susceptibility in Africans. (This is actually one of the reasons they justified using an African American cohort in this study-since they're an admixed population, there are some African Americans who are DARC positive).

This study is certainly not conclusive in terms of explaining the different HIV incidence/prevalence rates in different African populations. Indeed, a study carried out a few years ago showed that a cohort of commercial sex-workers in a Nairobi slum were resistant to HIV infection despite high exposure to the virus. The researchers in this study think there may be some genetic or other biological factor at play that confers immunity against HIV infection in these individuals. If indeed there is some sort of genetic factor at play, there definitely needs to be more research done, since there might even be different gene/protein interactions contributing to these differences in risk in different populations.

sylvia, were
written by Stephen Wanyama , July 29, 2008

I would like to ask, why do the figures for prevalence rates fluctuate so? I mean we are either dealing with the scourge and trending lower, or else failing to deal with it, and so trending higher. Are the surveys poorly done? Kenya was named alongside India and Zimbabwe last December as a country that had drastically slashed its prevalence rates. Now we are told, the picture is actually far uglier than 2003 even, let alone last year. What gives?

...
written by snkariuki , July 30, 2008

A variety of biological and behavioural factors should be taken into account when talking about incidence and prevalence rates of HIV/AIDS. The downward trend in the HIV/AIDS prevalence rate in countries like Kenya, Uganda and Zimbabwe could be due to the fact that the rate of mortality of HIV positive individuals succumbing to AIDS is equal to, or greater than the rate of incidence (i.e. new cases of HIV infection). Incidence rates may certainly be slowed down by increased preventative measures e.g. greater condom use. However, this doesn’t mean that incidence rates are falling dramatically; these rates are still high in these countries. However because mortality rates are on the rise and are indeed overtaking new infection cases, we see this stabilizing or even declining rates of prevalence.
The numbers in Kenya are certainly a cause for concern. According to today's dailies, Kenya’s HIV/AIDS prevalence rate has increased to nearly 8%, up from last year’s 5.1%. This shows that incidence rates have been very high all along, and indeed could now be rising much faster than mortality rates.
We hence need to focus on reducing incidence rates by stepping up the preventative measures already in place, in order to really control the HIV/AIDS epidemic.

Jibu Ya maswali
written by Omange , August 01, 2008

Munala

Yes HIV/AIDS appears to be wearing a female face more and more. It is thought that 60% of the HIV-1 infected people in Sub-Saharan Africa are women. This considering that out of the 33 million, currently living with HIV/AIDS cases, 70% are found in sub-saharan Africa. Here is what i think....The answer to this trend may not lie in some unique physiological property that Sub-Saharan African women poses, but may lie in the history of HIV disease itself. It appears that HIV/AIDS had its origins in Africa, contrary to previous beliefs that it was imported by tourists of European origin. Evidence is in a publication (1) in which researcher are documented to have detected RNA sequences in achieved blood Plasma samples as far back to 1950 dating. Further evidence can be deduced from the first diagnosis of HIV-1 in the male homosexuals in 1983, it would have take nothing less than 10-15 years or more from the date of acquisition to stage where the Pneumocystis carnii was first diagnosed leading to description of AIDS and isolation of HIV-1 virus, later.

A analysis of the genetic distribution, host preference and pathogeniscity, of Simian Immunodeficiency Virus (SIV), HIV-2 (less virulent and found mostly around West Africa) and HIV-1 (most virulent and most widely distributed); One can argue that the women of sub-saharan Africa may be closer to the 'epicenter' of SIV-HIV emergence. From where it spread to other parts of the world.

Back to the genital front, little genetic evidence, immunologic, physiological, behavioural or socio-economic factors can fully explain the HIV/AIDs statistic among Sub-saharan women.

My take home... HIV/AIDS was there before 1981 when it was first detected, and from the recent evidence of HIV-like RNA sequences in acheived Plasma samples, HIV has been longer than currently perceived, the length of it existence and origin (appears to be from SIV in Central-West Africa) may be instrumental in explaining the current HIV/AIDs demographics

Jibu ya Maswali
written by Omange , August 01, 2008

SKariuki

I have since been able to get a hold on the He et al 2008 Publication on the DARC gene and influence in HIV-1 transfection and susceptibility in Africans. We discussed the paper at length during our journal club and the following gaps remain unfilled and the DARC gene needs "more light" shed on it.

The validity of the DARC gene's influence on HIV-1 virion binding and dissemination, thereby influencing disease progression and "suscepibility". He Weijing and colleagues needed to have demonstrated using in vitro experiments the binding, dissemination and transfection of target cells by HIV bound to the RBCs. This they did remarkably. However, in vitro scenarios do not always represent the in vivo reality. Weijing He and colleagues appreciate this. Yet they use genetic epidemiologic models to compare the frequencies of the DARC /- in African American and other racial groups, from within their Wilford Hall Medicak Cohort and Human Genome Project database. They use the genetic frequencies of DARC /- and Cox regression model, as their basis for relating the influences of DARC gene presence or absence on CD4 T cell loss, HIV Associated demetia prevalence, disease progression and HIV-1 susceptibility. This analysis may be influenced by a large number of confounding factors. They consider only three confounding factors-MHC genotype (some HLA types are known to protect against HIV), CCR5 delta 32 deletion (protective against HIV albeit its occurence in African Americans i very minimal) and Admixture.

In as much as considering and factoring in the effect of these confounding factors on DARC -46C/C in African americans, they admit in their dicussion:-

Whereas, paradoxically, once infection occurs, the DARC –46C/C genotype confers a survival advantage to African Americans that is comparable in magnitude to the survival advantage conferred
by the CCR5-D32 genotype to European Americans. Whether
the DARC -46C/C genotype also increases the risk of infection
and conveys a survival advantage to African populations outside
the US remains unknown but would appear likely.

The in vivo interraction of the chemokine (levels of production, mechanism of release and retention) the levels of expression of DARC on RBCs and amount of HIV-1 virions that can bind on a RBC and required for the process to take place. How about the prevalence of HIV-1 disease in patients with Sickle cell anaemia or sickle cell trait (genetic disorder that is linked to Africans) and other immunological questions like the actual relation to the absence of the DARC protein with susceptibility in the natural set up.

In closure, i agree with you that the work done by Weijing and Weiss forms the basis for larger in vivo studies in the future to enhance the current understanding on its in vivo influences on HIV disease progression and HIV-1 susceptibility in both Africans, African American and other racial groups.

References
written by Omange , August 01, 2008

1 Korber et al 2000 -Timing the ancestor of the HIV-1 pandemic strains

2 David D. Ho1, and Paul D. Bieniasz1- HIV at 25, Cell May 16 2008

Kenya HIV/AIDS statistics
written by Omange , August 01, 2008

Stephen Wanyama

Allow me to read the most recent HIV/AIDs demographic trends released this week after the Kenya AIDS Indicator Survey. I will reply appropriately to the cause of the disproportionate prevalence rates across the provinces.

Thank you guys