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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

neutralization epitopes through mutations in gp41

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.

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.

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

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.

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.

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.

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.

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.

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

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

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

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%.

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).

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.

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.