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Pettifor A.,University of North Carolina at Chapel Hill | Pettifor A.,University of Witwatersrand | Bekker L.-G.,University of Cape Town | Hosek S.,Stroger Hospital of Cook County | And 8 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2013

Objective: To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight the existing gaps and priority areas for future research. Background: A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population. Methods: We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps. Results: Adolescent interventions fall into 3 main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, whereas promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group. Conclusions: Adolescents have unique needs with respect to HIV prevention, and, thus, interventions should be designed to most effectively reach out to this population with information and services that will be relevant to them. Copyright © 2013 by Lippincott Williams & Wilkins.


McCoy S.I.,University of California at Berkeley | Buzdugan R.,University of California at Berkeley | Padian N.S.,University of California at Berkeley | Musarandega R.,Elizabeth Glaser Pediatric AIDS Foundation | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Objective: To examine the uptake of services and behaviors in the prevention of mother-to-child HIV transmission (PMTCT) cascade in Zimbabwe and to determine factors associated with MTCT and maternal antiretroviral therapy (ART) or antiretroviral (ARV) prophylaxis. Design: Analysis of cross-sectional data from mother-infant pairs. Methods: We analyzed baseline data collected in 2012 as part of the impact evaluation of Zimbabwe's Accelerated National PMTCT Program. Using multistage cluster sampling, eligible mother-infant pairs were randomly sampled from the catchment areas of 157 facilities in 5 provinces, tested for HIV infection, and interviewed about PMTCT service utilization. Results: Of 8800 women, 94% attended ≥1 antenatal care visit, 92% knew their HIV serostatus during pregnancy, 77% delivered in a health facility, and 92% attended the 6-8 week postnatal visit. Among 1075 (12%) HIV-infected women, 59% reported ART/ARV prophylaxis and 63% of their HIV-exposed infants received ARV prophylaxis. Among HIV-exposed infants, maternal receipt of ART/ARV prophylaxis was protective against MTCT [adjusted prevalence ratio (PR a): 0.41, 95% confidence interval (CI): 0.23 to 0.74]. Factors associated with receipt of maternal ART/ARV prophylaxis included ≥4 antenatal care visits (PR a: 1.18, 95% CI: 1.01 to 1.38), institutional delivery (PR a: 1.31, 95% CI: 1.13 to 1.52), and disclosure of serostatus (PR a: 1.30, 95% CI: 1.12 to 1.49). Conclusions: These data from women in the community indicate gaps in the PMTCT cascade before the accelerated program, which may have been missed by examination of health facility data alone. These gaps were especially noteworthy for services targeted specifically to HIV-infected women and their infants, such as maternal and infant ART/ARV prophylaxis. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Ferrari G.,Duke University | Korber B.,Los Alamos National Laboratory | Goonetilleke N.,Weatherall Institute of Molecular Medicine | Liu M.K.P.,Weatherall Institute of Molecular Medicine | And 18 more authors.
PLoS Pathogens | Year: 2011

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.


Kidia K.K.,University of Oxford | Mupambireyi Z.,University College London | Mupambireyi Z.,Center for Sexual Health and Research | Cluver L.,University of Oxford | And 5 more authors.
PLoS ONE | Year: 2014

Introduction & Objectives: Due to the scale up of antiretroviral therapy, increasing numbers of HIV-infected children are living into adolescence. As these children grow and surpass the immediate threat of death, the issue of informing them of their HIV status arises. This study aimed to understand how perinatally-infected adolescents learn about their HIV-status as well as to examine their preferences for the disclosure process. Methods: In-depth interviews were conducted with 31 (14 male, 17 female) perinatally-infected adolescents aged 16-20 at an HIV clinic in Harare, Zimbabwe, and focused on adolescents' experiences of disclosure. In addition, 15 (1 male, 14 female) healthcare workers participated in two focus groups that were centred on healthcare workers' practices surrounding disclosure in the clinic. Purposive sampling was used to recruit participants. A coding frame was developed and major themes were extracted using grounded theory methods. Results: Healthcare workers encouraged caregivers to initiate disclosure in the home environment. However, many adolescents preferred disclosure to take place in the presence of healthcare workers at the clinic because it gave them access to accurate information as well as an environment that made test results seem more credible. Adolescents learned more specific information about living with an HIV-positive status and the meaning of that status from shared experiences among peers at the clinic. Conclusions: HIV-status disclosure to adolescents is distinct from disclosure to younger children and requires tailored, age-appropriate guidelines. Disclosure to this age group in a healthcare setting may help overcome some of the barriers associated with caregivers disclosing in the home environment and make the HIV status seem more credible to an adolescent. The study also highlights the value of peer support among adolescents, which could help reduce the burden of psychosocial care on caregivers and healthcare workers. © 2014 Kidia et al.


PubMed | University of Zimbabwe, Center for Sexual Health and Research, London School of Hygiene and Tropical Medicine and University College London
Type: | Journal: BMC public health | Year: 2015

Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally. Of note, Zimbabwe also provided nevirapine prophylaxis for HIV exposed babies, so the majority were giving nevirapine and CTX-p to their babies.Between Feb-Dec 2011, the first 20 HIV infected mothers identified were invited for in-depth interview 4-5months postnatally. Interviews were recorded, transcribed, translated and analysed thematically.All women desired their babys health above all else, and were determined to do all they could to ensure their wellbeing. They did not report problems remembering to give drugs. The babys apparent good health was a huge motivator for continued adherence. However, most women reported that their husbands were less engaged in HIV care, refusing to be HIV tested and in some cases stealing drugs prescribed for their wives for themselves. In two instances the man stopped the woman from giving CTX-p to the baby either because of fear of side effects or not appreciating its importance. Stigma continues to be an important issue. Mothers reported being reluctant to disclose their HIV status to other people so found it difficult to collect prescription refills from the HIV clinic for fear of being seen by friends/relatives. Some women reported that it was hard to administer the drugs if there were people around at home. Other challenges faced were stock-outs of CTX-p at the clinic, which occurred three times in 2011. The baby would then go without CTX-p if the woman could not afford buying at a private pharmacy.The study highlights that adherence knowledge and desire alone is insufficient to overcome the familial and structural barriers to maintaining CTX-p. Improving adherence to CTX-p among HEI will require interventions to improve male involvement, reduce HIV stigma in communities and ensure adequate supply of drugs.


Cella M.,University of Washington | Presti R.,University of Washington | Vermi W.,University of Brescia | Lavender K.,University of Oxford | And 10 more authors.
European Journal of Immunology | Year: 2010

The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8+ T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Ribeiro-dos-Santos P.,French Institute of Health and Medical Research | Turnbull E.L.,University of Oxford | Monteiro M.,French Institute of Health and Medical Research | Legrand A.,French Institute of Health and Medical Research | And 7 more authors.
Blood | Year: 2012

CD8 T cells lose the capacity to control HIV infection, but the extent of the impairment of CD8 T-cell functions and the mechanisms that underlie it remain controversial. Here we report an extensive ex vivo analysis of HIV-specific CD8 T cells, covering the expression of 16 different molecules involved in CD8 function or differentiation. This approach gave remarkably homogeneous readouts in different donors and showed that CD8 dysfunction in chronic HIV infection was much more severe than described previously: some Ifng transcription was observed, but most cells lost the expression of all cytolytic molecules and Eomesodermin and T-bet by chronic infection. These results reveal a cellular mechanism explaining the dysfunction of CD8 T cells during chronic HIV infection, as CD8 T cells are known to maintain some functionality when either of these transcription factors is present, but to lose all cytotoxic activity when both are not expressed. Surprisingly, they also show that chronic HIV and lymphocytic choriomeningitis virus infections have a very different impact on fundamental T-cell functions, "exhausted" lymphocytic choriomeningitis virus-specific cells losing the capacity to secrete IFN-γ but maintaining some cytotoxic activity as granzyme B and FasL are overexpressed and, while down-regulating T-bet, up-regulating Eomesodermin expression. © 2012 by The American Society of Hematology.


Bernays S.,London School of Hygiene and Tropical Medicine | Seeley J.,London School of Hygiene and Tropical Medicine | Rhodes T.,London School of Hygiene and Tropical Medicine | Mupambireyi Z.,Center for Sexual Health and Research | Mupambireyi Z.,University College London
Sociology of Health and Illness | Year: 2015

As paediatric HIV treatment has become increasingly available across the world, the global perinatally infected cohort is ageing. However, we know surprisingly little about what it is like to grow up with HIV in resource-stretched settings. We draw on findings from a prospective, qualitative study with HIV-positive children, their carers and healthcare workers from four clinics in Uganda and Zimbabwe to examine children's experiences of living with HIV on treatment. We consider how the HIV experience is made in a symbiotic relationship between children, carers and healthcare workers and shaped by broader discourses. Despite the radical development in prognosis for children, their experience of HIV is largely constructed in relation to a language of 'sickness' through the promotion of medicalised talk and the recounting of past illness stories. This narrow narrative framework both reflects and reproduces core dimensions of the lived experience of growing up with HIV, which emphasises an absence of resilient healthiness in the face of ongoing vulnerability and risk. The challenges that children encounter in articulating alternative narratives that prioritise the relative buoyancy of their health is indicative of the broader uncertainty that exists around the future for these children at this point in the epidemic. © 2014 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.


McCoy S.I.,University of California at Berkeley | Buzdugan R.,University of California at Berkeley | Mushavi A.,Ministry of Health and Child Welfare | Mahomva A.,Elizabeth Glaser Pediatric AIDS Foundation | And 3 more authors.
BMC Public Health | Year: 2015

Background: Food insecurity (FI) is the lack of physical, social, and economic access to sufficient food for dietary needs and food preferences. We examined the association between FI and women's uptake of services to prevent mother-to-child HIV transmission (MTCT) in Zimbabwe. Methods: We analyzed cross-sectional data collected in 2012 from women living in five of ten provinces. Eligible women were ≥16 years old, biological mothers of infants born 9-18 months before the interview, and were randomly selected using multi-stage cluster sampling. Women and infants were tested for HIV and interviewed about health service utilization during pregnancy, delivery, and post-partum. We assessed FI in the past four weeks using a subset of questions from the Household Food Insecurity Access Scale and classified women as living in food secure, moderately food insecure, or severely food insecure households. Results: The weighted population included 8,790 women. Completion of all key steps in the PMTCT cascade was reported by 49%, 45%, and 38% of women in food secure, moderately food insecure, and severely food insecure households, respectively (adjusted prevalence ratio (PRa)=0.95, 95% confidence interval (CI): 0.90, 1.00 (moderate FI vs. food secure), PRa=0.86, 95% CI: 0.79, 0.94 (severe FI vs. food secure)). Food insecurity was not associated with maternal or infant receipt of ART/ARV prophylaxis. However, in the unadjusted analysis, among HIV-exposed infants, 13.3% of those born to women who reported severe household food insecurity were HIV-infected compared to 8.2% of infants whose mothers reported food secure households (PR=1.62, 95% CI: 1.04, 2.52). After adjustment for covariates, this association was attenuated (PRa=1.42, 95% CI: 0.89, 2.26). There was no association between moderate food insecurity and MTCT in unadjusted or adjusted analyses (PRa=0.68, 95% CI: 0.43, 1.08). Conclusions: Among women with a recent birth, food insecurity is inversely associated with service utilization in the PMTCT cascade and severe household food insecurity may be positively associated with MTCT. These preliminary findings support the assessment of FI in antenatal care and integrated food and nutrition programs for pregnant women to improve maternal and child health. © 2015 McCoy et al.; licensee BioMed Central.


PubMed | Elizabeth Glaser Pediatric AIDS Foundation, Center for Sexual Health and Research, University of California at Berkeley and Ministry of Health and Child Welfare
Type: | Journal: BMC public health | Year: 2015

Food insecurity (FI) is the lack of physical, social, and economic access to sufficient food for dietary needs and food preferences. We examined the association between FI and womens uptake of services to prevent mother-to-child HIV transmission (MTCT) in Zimbabwe.We analyzed cross-sectional data collected in 2012 from women living in five of ten provinces. Eligible women were 16 years old, biological mothers of infants born 9-18 months before the interview, and were randomly selected using multi-stage cluster sampling. Women and infants were tested for HIV and interviewed about health service utilization during pregnancy, delivery, and post-partum. We assessed FI in the past four weeks using a subset of questions from the Household Food Insecurity Access Scale and classified women as living in food secure, moderately food insecure, or severely food insecure households.The weighted population included 8,790 women. Completion of all key steps in the PMTCT cascade was reported by 49%, 45%, and 38% of women in food secure, moderately food insecure, and severely food insecure households, respectively (adjusted prevalence ratio (PRa)=0.95, 95% confidence interval (CI): 0.90, 1.00 (moderate FI vs. food secure), PRa=0.86, 95% CI: 0.79, 0.94 (severe FI vs. food secure)). Food insecurity was not associated with maternal or infant receipt of ART/ARV prophylaxis. However, in the unadjusted analysis, among HIV-exposed infants, 13.3% of those born to women who reported severe household food insecurity were HIV-infected compared to 8.2% of infants whose mothers reported food secure households (PR=1.62, 95% CI: 1.04, 2.52). After adjustment for covariates, this association was attenuated (PRa=1.42, 95% CI: 0.89, 2.26). There was no association between moderate food insecurity and MTCT in unadjusted or adjusted analyses (PRa=0.68, 95% CI: 0.43, 1.08).Among women with a recent birth, food insecurity is inversely associated with service utilization in the PMTCT cascade and severe household food insecurity may be positively associated with MTCT. These preliminary findings support the assessment of FI in antenatal care and integrated food and nutrition programs for pregnant women to improve maternal and child health.

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