Hiv testing and counselling for women attending child health clinics: An opportunity for entry to prevent mother-to-child transmission and hiv treatment. Author



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Results:

Three polymorphisms in IRF-1, located at 619, the microsatellite region and 6516 of the gene, showed associations with resistance to HIV-1 infection. The 619A, 179 at IRF-1 microsatellite and 6516G alleles were associated with the HIV-1-resistant phenotype and a reduced likelihood of seroconversion. Peripheral blood mononuclear cells from patients with protective IRF-1 genotypes exhibited significantly lower basal IRF-1 expression and reduced responsiveness to exogenous IFN-gamma stimulation.


Conclusion:

Polymorphisms in the IRF-1 gene are associated with resistance to infection by HIV-1 and a lowered level of IRF-1 protein expression. This study adds IRF-1, a transcriptional immunoregulatory gene, to the list of genetic correlates of altered susceptibility to HIV-1. This is the first report suggesting that a viral transcriptional regulator might contribute to resistance to HIV-1. Further functional analysis on the role of IRF-1 polymorphisms and HIV-1 resistance is underway.



Cost effectiveness and delivery study for future HIV vaccines.
Author: Barth-Jones, D. C.; Cheng, H.; Kang, L. Y.; Kenya, P. R.; Odera, D.; Mosqueira, N. R.; Mendoza, W.; Portela, M. C.; Brito, C.; Tangcharoensathien, V.; Akaleephan, C.; Supantamart, S.; Patcharanarumol, W.; de Macedo Brigido, L. F.; Fonseca, M. G.; Sanchez, M.
Source : AIDS. 2005 Sep 2; 19(13):w1-6. .; Chang, M. L.; Osmanov, S.; Avrett, S.; Esparza, J., and Griffiths, U.
Abstract: Research teams from five countries, Brazil, China, Kenya, Peru and Thailand, have initiated a policy-maker survey on vaccine delivery, cost studies for future HIV vaccination programmes, and associated simulation modeling exercises analysing the relative cost-effectiveness of potential HIV vaccination strategies. The survey assesses challenges and opportunities for future country-level HIV vaccination strategies, providing data on the vaccine characteristics (e.g. vaccine efficacies for susceptibility, infectiousness and disease progression) and vaccination programme strategies to be considered in the cost-effectiveness modeling analyses. The study will provide decision-makers with modeling data on vaccination policy considerations that will assist in developing country-level capacities for future HIV vaccine policy adoption and effective delivery systems, and will help delineate the long-term financial requirements for sustainable HIV vaccination programmes. The WHO-UNAIDS HIV Vaccine Initiative and the collaborating researchers welcome comments or questions from policy makers, health professionals and other stakeholders in the public and private sectors about this effort to help advance policy and capacity related to future potential HIV vaccines.

HIV/AIDS and cultural practices in western Kenya: the impact of sexual cleansing rituals on sexual behaviours.
Author: R.; Ngare, D.; Sidle, J.; Ayuku, D.; Baliddawa, J., and Greene, J.
Source : Cult Health Sex. 2008 Aug; 10(6):587-99.
Abstract: This paper reports on an exploratory study examining the role of sexual cleansing rituals in the transmission of HIV among the Luo community in western Kenya. Data were collected using both in-depth interviews and focus group discussions. The study population consisted of 38 widows, 12 community elders and 44 cleansers. Data were collected on non-behavioural causes, behavioural causes and behavioural indicators associated with sexual rituals. Content analysis revealed five central themes: the effect of the ritual on sexual behaviours; factors contributing to the continued practice of the ritual, including a sub-theme on the commercialization of the ritual; the inseparable relationship between the sanctity of sex, prosperity and fertility of the land; and the effects of modernization on the ritual, including a sub-theme on the effects of mass media on HIV-prevention awareness campaigns. Causal factors of unchanging sexual behaviours are deeply rooted in traditional beliefs, which the community uphold strongly. These beliefs encourage men and women to have multiple sexual partners in a context where the use of condoms is rejected and little HIV testing is carried out.

Quantification of genital human immunodeficiency virus type 1 (HIV-1) DNA in specimens from women with low plasma HIV-1 RNA levels typical of HIV-1 nontransmitters.
Author: Benki, S.; McClelland, R. S.; Emery, S.; Baeten, J. M.; Richardson, B. A.; Lavreys, L.; Mandaliya, K., and Overbaugh, J.
Source : J Clin Microbiol. 2006 Dec; 44(12):4357-62.
Abstract: Studies of human immunodeficiency virus type 1 (HIV-1) transmission suggest that genital HIV-1 RNA and DNA may both be determinants of HIV-1 infectivity. Despite its potential role in HIV-1 transmission, there are limited quantitative data on genital HIV-1 DNA. Here we validated an in-house real-time PCR method for quantification of HIV-1 DNA in genital specimens. In reactions with 100 genomes to 1 genome isolated from a cell line containing one HIV-1 provirus/cell, this real-time PCR assay is linear and agrees closely with a commercially available real-time PCR assay specific for a cellular housekeeping gene. In mock genital samples spiked with low numbers of HIV-1-infected cells such that the expected HIV-1 DNA copy number/reaction was 100, 10, or 5, the average copy number/reaction was 80.2 (standard deviation [SD], 28.3), 9.1 (SD, 5.4), or 3.1 (SD, 2.1), respectively. We used this method to examine genital HIV-1 DNA levels in specimens from women whose low plasma HIV-1 RNA levels are typical of HIV-1 nontransmitters. The median HIV-1 DNA copy number in endocervical secretions from these women (1.8 HIV-1 DNA copies/10,000 cells) was lower than that for women with higher plasma HIV-1 RNA levels (16.6 HIV-1 DNA copies/10,000 cells) (P=0.04), as was the median HIV-1 DNA copy number in vaginal secretions (undetectable versus 1.0 HIV-1 DNA copies/10,000 cells). These data suggest that women with low plasma HIV-1 RNA and thus a predicted low risk of HIV-1 transmission have low levels of genital HIV-1 cell-associated virus. The assay described here can be utilized in future efforts to examine the role of cell-associated HIV-1 in transmission.

Infant feeding practices among HIV infected women receiving prevention of mother-to-child transmission services at Kitale District Hospital, Kenya.

Source : East Afr Med J. 2008 Apr; 85(4):156-61.
Abstract: Objectives:

To determine the types and modes of infant feeding practices among the HIV infected mothers on prevention of mother-to-child transmission (PMTCT) and attending MCH-FP clinic at Kitale District Hospital, Kenya.


Design: Descriptive cross-sectional study.
Setting:

Kitale District Hospital in Western Kenya within the maternal and child health and family planning (MCH-FP) and comprehensive care clinics.


Subjects:

A total of 146 respondents who had delivered 150 babies were recruited for this study.


Results:

Thirty five percent (52/150) of the babies were exclusively breastfed while 50% (75/150) were not breastfed at all and 14% (21/150) of the babies received mixed feeding. The length of exclusive breastfeeding ranged from 1-6 months with most (53%) women exclusively breastfeeding for two to three months. Only 13% of the women exclusively breastfed for five to six months. There was a strong relationship between mode of infant feeding and spouse's awareness of HIV status. Mothers who had disclosed their HIV status to their spouses were more likely not to breastfeed than mothers who had not disclosed their status (p < 0.05%). The choice of infant feeding method was also influenced by the socio-economic status of the mothers and nevirapine uptake. The level of education did not influence the mode of infant feeding.


Conclusion:

Infant feeding decisions were mainly influenced by the male partner's involvement and the socio economic status of the mother. Half of the respondents did not breastfeed at all. The duration of exclusive breastfeeding rarely reached six months. To encourage women to adhere to good infant feeding practices, involvement of their partners, family members as well as the community for support should be encouraged.



HIV-1 subtype A envelope variants from early in infection have variable sensitivity to neutralization and to inhibitors of viral entry.
Author: Blish, C. A.; Nedellec, R.; Mandaliya, K.; Mosier, D. E., and Overbaugh, J.
Source : AIDS. 2007 Mar 30; 21(6):693-702.
Abstract: Background:

An effective HIV-1 vaccine or microbicide must block the transmitted virus variants that initially establish a new infection; consequently, it is critical that such viruses be isolated and characterized.


Objective:

To evaluate HIV-1 envelope variants from early in infection from individuals infected heterosexually with subtype A HIV-1 for their sensitivity to antibody-mediated neutralization and to inhibitors of viral entry.


Methods:

Full-length subtype A HIV-1 envelope clones from 28-75 days postinfection were used to generate pseudoviruses for infection studies. The susceptibility of these pseudoviruses to neutralization by autologous and heterologous plasma and by monoclonal antibodies was examined. The sensitivity of these pseudoviruses to PSC-RANTES and TAK-779, inhibitors of CCR5, and to soluble CD4 (sCD4) was also evaluated. RESULTS: Pseudoviruses with subtype A HIV-1 envelopes from early in infection demonstrated a broad range of neutralization sensitivities to both autologous and heterologous plasma. However, neutralization by the monoclonal antibodies b12, 2G12, 4E10 and 2F5 was generally poor; notably, none of the 14 early virus variants were neutralized by 2G12 and only one was neutralized by b12. Viruses bearing these early CCR5-using envelopes were generally sensitive to the CCR5 inhibitors PSC-RANTES and TAK-779, but they demonstrated more variable sensitivity to sCD4.


Conclusions:

These subtype A HIV-1 variants, representing the viruses that must be blocked by antibody-based prevention strategies, vary in their susceptibility to neutralization. A subset of these HIV-1 variants from early in infection will be useful for screening candidate vaccines and microbicides.



Enhancing exposure of HIV-1 neutralization epitopes through mutations in gp41.
Author: Blish, C. A.; Nguyen, M. A., and Overbaugh, J. Enhancing exposure of HIV-1

neutralization epitopes through mutations in gp41


Source : PLoS Med. 2008 Jan 3; 5(1):e9.
Abstract: Background:

The generation of broadly neutralizing antibodies is a priority in the design of vaccines against HIV-1. Unfortunately, most antibodies to HIV-1 are narrow in their specificity, and a basic understanding of how to develop antibodies with broad neutralizing activity is needed. Designing methods to target antibodies to conserved HIV-1 epitopes may allow for the generation of broadly neutralizing antibodies and aid the global fight against AIDS by providing new approaches to block HIV-1 infection. Using a naturally occurring HIV-1 Envelope (Env) variant as a template, we sought to identify features of Env that would enhance exposure of conserved HIV-1 epitopes.


Methods and findings:

Within a cohort study of high-risk women in Mombasa, Kenya, we previously identified a subtype A HIV-1 Env variant in one participant that was unusually sensitive to neutralization. Using site-directed mutagenesis, the unusual neutralization sensitivity of this variant was mapped to two amino acid mutations within conserved sites in the transmembrane subunit (gp41) of the HIV-1 Env protein. These two mutations, when introduced into a neutralization-resistant variant from the same participant, resulted in 3- to >360-fold enhanced neutralization by monoclonal antibodies specific for conserved regions of both gp41 and the Env surface subunit, gp120, >780-fold enhanced neutralization by soluble CD4, and >35-fold enhanced neutralization by the antibodies found within a pool of plasmas from unrelated individuals. Enhanced neutralization sensitivity was not explained by differences in Env infectivity, Env concentration, Env shedding, or apparent differences in fusion kinetics. Furthermore, introduction of these mutations into unrelated viral Env sequences, including those from both another subtype A variant and a subtype B variant, resulted in enhanced neutralization susceptibility to gp41- and gp120-specific antibodies, and to plasma antibodies. This enhanced neutralization sensitivity exceeded 1,000-fold in several cases.


Conclusions:

Two amino acid mutations within gp41 were identified that expose multiple discontinuous neutralization epitopes on diverse HIV-1 Env proteins. These exposed epitopes were shielded on the unmodified viral Env proteins, and several of the exposed epitopes encompass desired target regions for protective antibodies. Env proteins containing these modifications could act as a scaffold for presentation of such conserved domains, and may aid in developing methods to target



Late marriage and the HIV epidemic in sub-Saharan Africa.
Source : Popul Stud (Camb). 2007 Mar; 61(1):73-83.
Abstract: The causes of large variation in the sizes of HIV epidemics among countries in sub-Saharan Africa are not well understood. Here we assess the potential roles of late age at marriage and a long period of premarital sexual activity as population risk factors, using ecological data from 33 sub-Saharan African countries and with individual-level data from Demographic and Health Surveys (DHS) in Kenya and Ghana in 2003. The ecological analysis finds a significant positive correlation between HIV prevalence and median age at first marriage, and between HIV prevalence and interval between first sexual intercourse and first marriage. The individual-level analysis shows that HIV infection per year of exposure is higher before than after first marriage. These findings support the hypothesis of a link between a high average age at marriage and a long period of premarital intercourse during which partner changes are relatively common and facilitate the spread of HIV.

Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden. Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden.
Author: Bonnet, M. M.; Pinoges, L. L.; Varaine, F. F.; Oberhauser, B. B.; O'Brien, D. D.; Kebede, Y. Y.; Hewison, C. C.; Zachariah, R. R., and Ferradini, L. L.
Source : AIDS. 2006 Jun 12; 20(9):1275-9.
Abstract: Background:

HAART reduces tuberculosis (TB) incidence in people living with HIV/AIDS but those starting HAART may develop active TB or subclinical TB may become apparent in the immune reconstitution inflammatory syndrome.


Objective:

To measure the incidence rate of notified TB in people receiving HAART in five HIV programmes occurring in low-resource countries with a high TB/HIV burden.


Methods:

A retrospective review in five Medecins Sans Frontieres programmes (Cambodia, Thailand, Kenya, Malawi and Cameroon) allowed incidence rates of notified TB to be calculated based on follow-up time after HAART initiation.


Result:

Among 3151 patients analysed, 90% had a CD4 cell count of < 200 cells/mul. Median follow-up time ranged from 3.7 months in Thailand or Kenya to 11.1 months in Cambodia. Incidence rates were 7.6, 10.4, 17.6, 14.3 and 4.8/100 person-years for pulmonary TB and 12.7, 4.3, 6.9, 2.1 and 0/100 person-years for extra-pulmonary TB in the programmes in Cambodia, Thailand, Kenya, Malawi and Cameroon, respectively. Overall, 62.3% of pulmonary TB and 54.9% of extra-pulmonary TB were diagnosed within 3 months after HAART initiation.


Conclusion:

High incidence rates of notified TB under HAART in programmes held in poor-resource countries were observed; these were likely to include both undiagnosed prevalent TB at HAART initiation and subclinical TB developing during the immune reconstitution inflammatory syndrome. This raises operational issues concerning TB diagnosis and treatment of TB/HIV-coinfected patients and prompts for urgent TB and HIV care integration.



Longitudinal comparison of chemokines in breastmilk early postpartum among HIV-1-infected and uninfected Kenyan women.
Author: Bosire, R.; Guthrie, B. L.; Lohman-Payne, B.; Mabuka, J.; Majiwa, M.; Wariua, G.; Mbori-Ngacha, D.; Richardson, B.; John-Stewart, G., and Farquhar, C
Source : Breastfeed Med. 2007 Sep; 2(3):129-38.
Abstract: Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared cross-sectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum. For both HIV-1-infected and uninfected women, breastmilk chemokine levels were highest at day 5 for MIP-1alpha, MIP-1beta, and SDF-1alpha, and subsequently decreased. RANTES levels remained constant over the follow-up period among HIV-1-uninfected women, and increased moderately among HIV-1-infected women. For MIP-1beta and RANTES, breastmilk levels were significantly higher among HIV-1-infected women compared to uninfected women early postpartum. In addition, HIV-1-infected women transmitting HIV-1 to their infant had consistently higher breastmilk RANTES levels than those who did not transmit, with the greatest difference observed at 1 month (2.68 vs. 2.21 log10 pg/mL, respectively; p = 0.007). In summary, all four chemokines were most elevated within the first month postpartum, a period of high transmission risk via breastmilk. MIP-1beta and RANTES levels in breastmilk were higher among HIV-1-infected women than among uninfected women, and breastmilk RANTES was positively associated with vertical transmission in this study, consistent with results from our earlier cohort.

Effect of CCR2 chemokine receptor polymorphism on HIV type 1 mother-to-child transmission and child survival in Western Kenya. AIDS Res Hum Retroviruses.
Author: Brouwer, K. C.; Yang, C.; Parekh, S.; Mirel, L. B.; Shi, Y. P.; Otieno, J.; Lal, A. A., and Lal, R. B.
Source : AIDS Res Hum Retroviruses. 2005 May; 21(5):358-62.
Abstract: The effect of CCR2 polymorphism on HIV-1 mother-to-child transmission and disease progression has not been explored in depth within Africa. As the CCR2-64I variant of this putative HIV coreceptor has been associated with slower progression to AIDS in adults, the current study was undertaken to examine the relationship between CCR2 polymorphism and HIV-1 perinatal transmission and child survival in western Kenya. CCR2 genotype was determined for 445 HIV-seropositive mothers and their infants. The CCR2-64I allele frequency of both mothers and children did not differ by HIV-1 transmission status, regardless of maternal viral load, viral subtype, immune status, or placental malaria status. For infants who acquired HIV perinatally (n = 78), there was no association between CCR2 genotype and viral load upon infection or survival rate over the 2-year follow-up. Our results do not indicate an effect of CCR2-64I on perinatal HIV transmission and survival in Kenyan children.

Identification of differentially expressed proteins in the cervical mucosa of HIV-1-resistant sex workers.
Author: Burgener, A.; Boutilier, J.; Wachihi, C.; Kimani, J.; Carpenter, M.; Westmacott, G.; Cheng, K.; Ball, T. B., and Plummer, F.
Source : J Proteome Res. 2008 Oct; 7(10):4446-54.
Abstract: Novel tools are necessary to understand mechanisms of altered susceptibility to HIV-1 infection in women of the Pumwani Sex Worker cohort, Kenya. In this cohort, more than 140 of the 2000 participants have been characterized to be relatively resistant to HIV-1 infection. Given that sexual transmission of HIV-1 occurs through mucosal surfaces such as that in the cervicovaginal environment, our hypothesis is that innate immune factors in the genital tract may play a role in HIV-1 infection resistance. Understanding this mechanism may help develop microbicides and/or vaccines against HIV-1. A quantitative proteomics technique (2D-DIGE: two-dimensional difference in-gel electrophoresis) was used to examine cervical mucosa of HIV-1 resistant women ( n = 10) for biomarkers of HIV-1 resistance. Over 15 proteins were found to be differentially expressed between HIV-1-resistant women and control groups ( n = 29), some which show a greater than 8-fold change. HIV-1-resistant women overexpressed several antiproteases, including those from the serpin B family, and also cystatin A, a known anti-HIV-1 factor. Immunoblotting for a selection of the identified proteins confirmed the DIGE volume differences. Validation of these results on a larger sample of individuals will provide further evidence these biomarkers are associated with HIV-1 resistance and could help aid in the development of effective microbicides against HIV-1.

Correlation of CD4 counts and CD4/CD8 ratio with HIV-infection associated oral manifestations.
Author: Butt, F. M.; Vaghela, V. P., and Chindia, M. L. Correlation of CD4 counts and CD4/CD8 ratio with HIV-infection associated oral manifestations.
Source : East Afr Med J. 2007 Aug; 84(8):383-8.
Abstract: Background:

The relationship between oral lesions arising from HIV infection and CD4/CD8 cell ratios is of relevance in clinical assessment of immune suppression.


Objective:

To correlate the prevalence of oral manifestations arising from HIV infection and the levels of CD4/CD8 cell ratios.


Design: A cross-sectional study.
Setting: Kenyatta National Hospital, Nairobi, Kenya.
Subjects:

Two hundred and seven HIV-infected patients in medical wards were recruited in the study.


Results:

Seventy eight (37.7%) were male and 129 (62.3%) female, with an age range of 18-73 years (mean=34.81 years). Oral manifestations encountered with highest prevalence in the oral cavity included: hyperplastic candidosis (labial mucosa) 15%, erythematous candidosis (gingival) 5%, angular cheilitis 32.4%, herpes simplex (corner of the mouth) 0.5%, persistent oral ulceration (labial mucosa) 0.5%, Parotid enlargement 2% and Kaposis sarcoma (hard/soft palate) 2.9%.


Conclusion:

The prevalence of oral manifestations was higher with low CD4 count <200 cell/mm3 and mean CD4/CD8<0.39(95%CI 0.32-0.48).



Integrating nutrition security with treatment of people living with HIV: lessons from Kenya.
Author: Byron, E.; Gillespie, S., and Nangami, M
Source : Food Nutr Bull. 2008 Jun; 29(2):87-97.
Abstract: Background:

The increased caloric requirements of HIV-positive individuals, undesirable side effects of treatment that may be worsened by malnutrition (but alleviated by nutritional support), and associated declines in adherence and possible increased drug resistance are all justifications for developing better interventions to strengthen the nutrition security of individuals receiving antiretroviral treatment.


Objective:

To highlight key benefits and challenges relating to interventions aimed at strengthening the nutrition security of people living with HIV who are receiving antiretroviral treatment.



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