Challenges in PMTCT antiretroviral adherence in northern KwaZulu-Natal, South Africa.

BACKGROUND: Women living with HIV in sub-Saharan Africa face significant challenges in accessing HIV care and adhering to antiretroviral therapy. Most reports have focused on issues relating to long-term adherence such as those surrounding stigma and disclosure, hunger, cultural factors, lack of accurate health information, lack of social support, medication side effects and overcrowded health systems. Information related to the challenges facing pregnant women when taking antiretrovirals for prophylactic purposes is limited. The "Kesho Bora Study" is a multicentre prevention of mother-to-child transmission (PMTCT) trial in sub-Saharan Africa evaluating the PMTCT efficacy of triple therapy until cessation of breast feeding compared to short course zidovudine monotherapy in a predominantly breast feeding population. Following unexplained discrepancies during objective adherence assessments, a sub-study was conducted at one site to examine the underlying adherence issues. METHODS: The counselling and clinical notes of all 100 enrolled Zulu women were examined. Extracted information was supplemented by unstructured, free-ranging interviews conducted by trained adherence counsellors on 43 consecutive women attending the trial clinic over a two-week period. Adherence was defined as good (>95% adherence), or poor (<95% adherence). RESULTS: Reasons provided for sub-optimal adherence included therapy misconceptions/misunderstandings, antiretroviral use by relatives, domestic violence, poverty and issues relating to disclosure and stigma. About 61% (57/94) of antenatal women had good adherence with their PMTCT prophylaxis, with no significant difference shown between those taking the long and short course. CONCLUSION: Antenatal women in northern rural KwaZulu-Natal face significant challenges in taking antiretroviral PMTCT prophylaxis.

Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.

In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 ( n = 259) expression are associated with differences in HIV-1-specific CD8 (+) T cell responses. The overall breadth and magnitude of HIV-1-specific CD8(+) T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801-restricted CD8 (+) T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8 (+) T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression.