Acceptability and preferences for safer conception HIV prevention strategies: a qualitative study

Safer conception strategies to reduce HIV transmission risk include antiretroviral therapy (ART) for HIV-positive partners, pre-exposure prophylaxis (PrEP) for HIV-negative partners, condomless sex limited to fertile periods, and home-based self-insemination. Resistance to taking treatment or cultural concerns may limit uptake of strategies and intervention success. Understanding the acceptability and preferences between different approaches is important to optimize service delivery. Between February-July 2013, 42 adults (21 HIV-positive and 21 HIV-negative) receiving primary care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, participated in focus group discussions or in-depth interviews. Themes were analyzed using a grounded theory approach. Acceptability of antiretroviral-based (ARV) strategies varied. Concerns over side effects, ARV treatment duration, and beliefs that treatment is only for the sick were common barriers, however desperation for a child was noted as a facilitator for uptake. HIV-negative men and HIV-positive women had favorable attitudes towards self-insemination, though paternity and safety concerns were raised. Self-insemination was generally preferred over PrEP by HIV-negative men, and ARV-based strategies were preferred by couples with HIV-negative female partners, despite concerns raised about condomless sex while virally suppressed. Knowledge about the fertile window was low. A strong counselling component will be required for effective uptake and adherence to safer conception services

“I don't know if this is right … but this is what I'm offering”: healthcare provider knowledge, practice, and attitudes towards safer conception for HIV-affected couples in the context of Southern African guidelines

The 2011 guidelines for safer conception for HIV-affected individuals and couples were adopted by the South African Department of Health in December 2012. We assessed implementation gaps and facilitators and barriers to delivering safer conception services through examining patient and healthcare provider (HCP) experiences. At Witkoppen Health and Welfare Centre, a primary care clinic in Johannesburg, we conducted in-depth interviews (IDIs) with 9 HCPs (doctors, nurses and counselors) and IDIs and focus group discussions with 42 HIV-affected men and women interested in having a child. Data were analyzed using a grounded theory approach. HCPs were supportive of fertility intentions of HIV-affected couples and demonstrated some knowledge of safer conception methods, especially ART initiation to suppress viral load in infected partners. Unfortunately, HCPs did not follow the key recommendation that HCPs initiate conversations on fertility intentions with HIV-affected men and women. Providers and clients reported that conversations about conception only occur when client-initiated, placing the onus on HIV-affected individuals. Important barriers underlying this were the misconception held by some HCPs that uninfected partners in serodiscordant partnerships are “latently” infected and the desire by most HCPs to protect or control knowledge around fertility and safer conception methods out of concern over what clients will do with this knowledge before they are virally suppressed or ready to conceive. Almost all participants who had conceived or attempted conception did so without safer conception methods knowledge. HCP concern over conception readiness, perception of what clients will do with safer conception knowledge, and gaps in safer conception knowledge prevent HCPs from initiating conversations with HIV-affected patients on the issue of childbearing. Examining these findings in the context of existing South African guidelines illuminates areas that need to be addressed to facilitate implementation of the guidelines

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

CISAR – A Modular Database System as a Basis for Analysis and Documentation of Spatial Information

Abstract Background Since 2010, the World Health Organization recommends lifelong antiretroviral treatment for all women living with HIV, and exclusive breastfeeding for six-months followed by breastfeeding until 24-months for all HIV positive mothers. Nevertheless, many mothers living with HIV do not initiate breastfeeding or stop prematurely, and many countries are still in the process of updating their national infant feeding guidelines to align with World Health Organization recommendations. We sought to understand uptake of breastfeeding and factors that influence decision-making regarding infant feeding in women living with and without HIV who receive ante- and postnatal care at a primary healthcare setting. Methods Programmatic data on infant feeding intentions and practices among women attending an ante-and postnatal clinic service at a primary care clinic in Johannesburg, South Africa were summarized using descriptive statistics. Qualitative interviews were conducted with 12 healthcare providers, 12 women living with HIV who were breastfeeding and 10 who were formula feeding. Interviews were analyzed using a content analysis approach. Results Pregnant women living with HIV were less likely to express an intent to breastfeed (71% vs 99%). During the first 6 months postpartum, mothers living with HIV were also less likely to exclusively breastfeed compared to HIV-negative mothers. Mixed messages during infant feeding counselling, social and economic factors, and fear of HIV transmission influenced women’s choices to initiate and continue breastfeeding. Conclusions As infant feeding guidelines for women living with HIV have evolved rapidly in the past 10 years, uniform messages on the low risk of mother-to-child transmission of HIV associated with breastfeeding while on ART and on introduction of complementary foods after 6 months of age are needed

Characterization of Treponema denticola pyrF encoding orotidine-5′-monophosphate decarboxylase

The Treponema denticola ATCC 35405 genome annotation contains most of the genes for de novo pyrimidine biosynthesis. To initiate characterization of pyrimidine synthesis in Treponema , we focused on TDE2110 (the putative pyrF , encoding orotidine-5′-monophosphate decarboxlyase). Unlike the parent strain, an isogenic pyrF mutant was resistant to 5-fluoroorotic acid. In complex medium, growth of the pyrF mutant was independent of added uracil, indicating activity of a uracil uptake/salvage pathway. Transcription of pyrF was greatly reduced in T. denticola grown in excess uracil, demonstrating that de novo pyrimidine synthesis is regulated and suggesting a feedback mechanism. Treponema denticola PyrF complemented uracil auxotrophy in an Escherichia coli pyrF mutant. This study provides biochemical confirmation of T. denticola genome predictions of de novo and salvage pyrimidine pathways and provides proof of concept that pyrF has potential as a selectable marker in T. denticola .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75261/1/j.1574-6968.2006.00589.x.pd

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study

Abstract Background South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Methods Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI Results The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0–14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01–1.05), male gender (OR = 2.70, 95 % CI = 1.55–4.70), marital status (OR = 2.00, 95 % CI = 1.31–3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04–4.31). Conclusions The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study

Abstract Background South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Methods Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI Results The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0–14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01–1.05), male gender (OR = 2.70, 95 % CI = 1.55–4.70), marital status (OR = 2.00, 95 % CI = 1.31–3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04–4.31). Conclusions The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty