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Find video protocols related to scientific articles indexed in Pubmed.
Plasma cytokine levels and risk of HIV-1 transmission and acquisition: a nested case-control study among HIV-1 serodiscordant couples.
J. Infect. Dis.
PUBLISHED: 11-13-2014
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?A heightened pro-inflammatory state has been hypothesized to enhance HIV-1 transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.
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Variants in host viral replication cycle genes are associated with heterosexual HIV-1 acquisition in Africans.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-28-2014
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We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.
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Frequent genital HSV-2 shedding among women during labor in Soweto, South Africa.
Infect Dis Obstet Gynecol
PUBLISHED: 01-21-2014
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Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor.
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CD4 counts and viral loads of newly diagnosed HIV-infected individuals: implications for treatment as prevention.
PLoS ONE
PUBLISHED: 01-01-2014
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To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines.
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Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans.
J. Infect. Dis.
PUBLISHED: 12-10-2013
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Objective.?We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples.Methods.?Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls.Results.?TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR]=0.7; p=0.03 and OR=0.9, p=0.5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression.Conclusion.?TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.
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Intimate partner violence and condom and diaphragm nonadherence among women in an HIV prevention trial in southern Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 10-30-2013
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We longitudinally examined the effect of intimate partner violence (IPV) on condom and diaphragm nonadherence among women in the Methods for Improving Reproductive Health in Africa study, a phase III HIV prevention trial in southern Africa.
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Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.
J. Infect. Dis.
PUBLISHED: 07-30-2013
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Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.
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Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.
AIDS Res. Hum. Retroviruses
PUBLISHED: 06-06-2013
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Plasma HIV-1 RNA set point is an important predictor of HIV-1 disease progression. We hypothesized that inoculum size and HIV-1 exposure prior to HIV-1 transmission may modulate set point. We evaluated predictors of set point among 141 African HIV-1 seroconverters and their HIV-1-infected study partners. We compared characteristics of seroconverters and their HIV-1-infected partners and HIV-1 set point. Data were from a clinical trial of genital HSV-2 suppression with acyclovir to reduce HIV-1 transmission in HIV-1 serodiscordant couples with HIV-1 transmission linkage assigned through virus sequencing. Our analysis includes data from all transmissions including those with transmission linkage to the HIV-1-infected "source partner" and those that were not linked to their HIV-1-infected study partner. In multivariable analysis, higher plasma HIV-1 in source partners was associated with higher seroconverter set point ( + 0.44 log10 copies/ml per log(10) source partner plasma HIV-1, p < 0.001). In addition, bacterial vaginosis (BV) among female source partners near the time of infection was associated with higher set point in their male seroconverters ( + 0.49 log(10), p = 0.04). Source partner characteristics associated with lower set point included male circumcision ( - 0.63 log(10), p = 0.03) and assignment to acyclovir ( - 0.44 log10, p = 0.02). The proportion of variation in set point explained by plasma HIV-1 RNA of the source partner, after controlling for other factors, was 0.06. Source partner plasma HIV-1 level is the most significant predictor of seroconverter set point, possibly reflecting characteristics of the transmitted virus. Acyclovir use, BV among women source partners, and circumcision among male source partners may alter the set point by affecting transmitted virus inoculum in the source partners genital compartment.
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Oral and injectable contraception use and risk of HIV acquisition among women in sub-Saharan Africa.
AIDS
PUBLISHED: 05-24-2013
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To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe.
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HIV testing and counseling leads to immediate consistent condom use among South African stable HIV-discordant couples.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-09-2013
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Effective behavioral HIV prevention is needed for stable HIV-discordant couples at risk for HIV, especially those without access to biomedical prevention. This analysis addressed whether HIV testing and counseling with ongoing counseling and condom distribution lead to reduced unprotected sex in HIV-discordant couples.
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Identification and characterisation of vaginal lactobacilli from South African women.
BMC Infect. Dis.
PUBLISHED: 01-18-2013
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Bacterial vaginosis (BV), which is highly prevalent in the African population, is one of the most common vaginal syndromes affecting women in their reproductive age placing them at increased risk for sexually transmitted diseases including infection by human immunodeficiency virus-1. The vaginal microbiota of a healthy woman is often dominated by the species belonging to the genus Lactobacillus namely L. crispatus, L. gasseri, L. jensenii and L. iners, which have been extensively studied in European populations, albeit less so in South African women. In this study, we have therefore identified the vaginal Lactobacillus species in a group of 40 African women from Soweto, a township on the outskirts of Johannesburg, South Africa.
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Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.
J. Infect. Dis.
PUBLISHED: 10-11-2011
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The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events.
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Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study.
Lancet Infect Dis
PUBLISHED: 10-03-2011
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Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners.
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"Group sex" parties and other risk patterns: A qualitative study about the perceptions of sexual behaviors and attitudes of adolescents in Soweto, South Africa.
Vulnerable Child Youth Stud
PUBLISHED: 08-23-2011
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This study explored perceptions about sexual behaviors and attitudes of adolescents living in Soweto, Johannesburg, South Africa, from the perspective of parents, counselors and adolescents. A qualitative methodology was applied. Nine focus group discussions (FGDs) were held; three with parents of adolescents, two with counselors who work with adolescents, two with female adolescents aged 16-18 years and two with male adolescents aged 16-18 years. In total, 80 participants were recruited from in and around Soweto. FGDs were guided by a semi-structured interview guide, audio-recorded, transcribed verbatim and translated into English. Data were analyzed using Maxqda, a qualitative software analysis program. There were eight key themes related to adolescent sexuality and perceived attitudes towards relationships. Five themes were common to all participant groupings (parents, counselors and adolescents): (1) dating during adolescence, (2) adolescent females dating older males, (3) condom use amongst adolescents, (4) pregnancy and (5) homosexuality. (6) Sex as a regular and important activity among adolescents and (7) group sex practices among adolescents emerged as themes from adolescent and counselor FGDs. Lastly, (8) the role of the media as an influence on adolescent sexuality was common to adolescent and parent groups. Risky sexual behaviors continue among adolescents, with group sex parties a concerning emergent phenomenon that necessitates further study. HIV, other STIs and pregnancy prevention interventions should address multiple levels of influence to address context-specific influences.
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Antiretroviral therapy refusal among newly diagnosed HIV-infected adults.
AIDS
PUBLISHED: 08-12-2011
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To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto, South Africa.
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Willingness to participate in biomedical HIV prevention studies after the HVTN 503/Phambili trial: a survey conducted among adolescents in Soweto, South Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-19-2011
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Adolescents may be appropriate for inclusion in biomedical HIV prevention trials. Adolescents overall willingness to participate (WTP) in biomedical HIV prevention trials was examined, including after the prematurely discontinued phase IIb HVTN 503/Phambili HIV vaccine trial, in Soweto, South Africa.
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Impact of learning HIV status on contraceptive use in the MIRA trial.
J Fam Plann Reprod Health Care
PUBLISHED: 07-11-2011
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We examined the effect of becoming HIV-positive on contraceptive practices in a Phase III randomised controlled trial of the diaphragm for HIV prevention. We coded self-reported contraceptive use into seven categories of methods in order of effectiveness. We compared the proportion using each category of contraception at baseline and last visit between women who did and did not become HIV-positive. We compared changes in the proportion using each category of contraception from baseline to last visit and calculated the percentage of women that moved to a more or less effective method category or stayed the same. We examined immediate and long-term changes in contraceptive use category after learning HIV-positive status.
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Determinants of differential HIV incidence among women in three southern African locations.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-10-2011
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We explored factors associated with differential HIV incidence among women participating in a HIV prevention trial in Harare, Durban, and Johannesburg. The trial had shown no effect of the intervention (diaphragm and lubricant gel) on HIV incidence.
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Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
PLoS ONE
PUBLISHED: 06-08-2011
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Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.
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Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study.
Lancet Infect Dis
PUBLISHED: 05-11-2011
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The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C.
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Changes in sexual risk behavior before and after HIV seroconversion in Southern African women enrolled in a HIV prevention trial.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-07-2011
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We examine changes in sexual risk behaviors before and after HIV seroconversion in southern African women enrolled in the Methods for Improving Reproductive Health in Africa trial.
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The effect of the vaginal diaphragm and lubricant gel on acquisition of HSV-2.
Sex Transm Infect
PUBLISHED: 03-29-2011
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In the context of a multisite HIV prevention trial in Southern African women, we examined the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens) and condoms compared to condoms alone on the incidence of herpes simplex virus type 2 (HSV-2) infections.
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Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa.
J Int AIDS Soc
PUBLISHED: 03-01-2011
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Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low.
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Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.
PLoS Med.
PUBLISHED: 02-22-2011
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Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.
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Who gets tested for HIV in a South African urban township? Implications for test and treat and gender-based prevention interventions.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-17-2011
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With increasing calls for linking HIV-infected individuals to treatment and care via expanded testing, we examined sociodemographic and behavioral characteristics associated with HIV testing among men and women in Soweto, South Africa.
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Performance of the Focus HerpeSelect-2 enzyme immunoassay for the detection of herpes simplex virus type 2 antibodies in seven African countries.
Sex Transm Infect
PUBLISHED: 02-09-2011
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To compare the performance of the Focus HerpeSelect-2 enzyme immunoassay (EIA) with the gold standard herpes simplex virus (HSV) type 2 western blot, among HIV-1-uninfected men and women in east and southern Africa.
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African women recently infected with HIV-1 and HSV-2 have increased risk of acquiring Neisseria gonorrhoeae and Chlamydia trachomatis in the Methods for Improving Reproductive Health in Africa trial.
Sex Transm Dis
PUBLISHED: 02-01-2011
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Neisseria gonorrhoeae and Chlamydia trachomatis are 2 common causative agents of cervical bacterial sexually transmitted infections (STI). Against the background of the concurrent epidemics of STIs and HIV in sub-Saharan Africa, we examined the effect of HIV-1 and HSV-2 on acquiring N. gonorrhoeae and C. trachomatis in a cohort of southern African women at risk for HIV infection.
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Contraception use and effectiveness among women in a trial of the diaphragm for HIV prevention.
Contraception
PUBLISHED: 01-26-2011
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There is little data on contraceptive effectiveness or use patterns from sub-Saharan Africa.
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International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations.
Vaccine
PUBLISHED: 01-09-2011
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Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.
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Cofactors that may influence vaccine responses.
Curr Opin HIV AIDS
PUBLISHED: 10-28-2010
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This review summarizes recent developments related to cofactors that may influence response to vaccination.
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Growth of infants born to HIV-infected women in South Africa according to maternal and infant characteristics.
Trop. Med. Int. Health
PUBLISHED: 10-20-2010
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To evaluate growth parameters assessed by weight and length in HIV-infected and HIV-uninfected infants born to HIV-infected mothers in South Africa from birth to 6 months of age.
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Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics.
AIDS
PUBLISHED: 09-03-2010
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In light of increasing access to HAART in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics.
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Patient referral from nurses to doctors in a nurse-led HIV primary care clinic in South Africa: implications for training and support.
AIDS Care
PUBLISHED: 08-17-2010
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Health services in sub-Saharan Africa are under great pressure to provide adequate clinical care due to the continued HIV epidemic, and nurse-driven models of care are one means to address physician shortages. This case-control study examines the reasons for and correlates of patient referral from nurses to physicians at HIV primary care clinics in South Africa prior to initiating antiretroviral treatment. Ninety-seven HIV-infected cases who required physician consolation and 160 controls who did not require physician consultation (matched on gender, age, and date of clinic visit) were consecutively enrolled at both an urban and rural HIV primary care clinic during a 12-month period beginning in March 2006. Univariate and multivariate logistic regression models were used to assess correlates of patient referral to a physician. Cases were more likely to have lower CD4 cell counts and have WHO Stages III and IV disease compared to controls (p<0.05). Predictors of patient referral were a CD4 cell count between 50 and 200 cells/µl (adj OR: 5.27, 95% CI: 2.16-12.88, p<0.0001), a CD4 cell count below 50 cells/µl (adj OR: 3.47, 95% CI: 1.12-10.78, p=0.032), and Stage IV disease (adj OR: 4.58, 95% CI: 1.35-15.60, p=0.015). Additionally, the following ICD-10 clinical diagnoses were associated with patient referral: tuberculosis, aplastic and other anemias, and lower respiratory tract infection (p<0.05). Nurses can provide adequate clinical and diagnostic management for certain clinical conditions to HIV-infected patients. Further studies are needed to examine specifically how HIV healthcare delivery can be scaled-up in resource-limited settings with a high burden of HIV, but with a minimal healthcare infrastructure.
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Morbidity and mortality among infants born to HIV-infected women in South Africa: implications for child health in resource-limited settings.
J. Trop. Pediatr.
PUBLISHED: 07-03-2010
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We examined correlates of infant morbidity and mortality within the first 3 months of life among HIV-exposed infants receiving post-exposure antiretroviral prophylaxis in South Africa.
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Epidemiological synergy of Trichomonas vaginalis and HIV in Zimbabwean and South African women.
Sex Transm Dis
PUBLISHED: 06-22-2010
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Trichomonas vaginalis (T. vaginalis) is the most common nonviral sexually transmitted infection in the world. Despite the coexisting global epidemics of T. vaginalis and HIV, little attention has focused on the emerging evidence that T. vaginalis increases susceptibility to, and potentially transmission of, HIV.
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A steady state of CD4+ T cell memory maturation and activation is established during primary subtype C HIV-1 infection.
J. Immunol.
PUBLISHED: 04-02-2010
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The functional integrity of CD4(+) T cells is crucial for well-orchestrated immunity and control of HIV-1 infection, but their selective depletion during infection creates a paradox for understanding a protective response. We used multiparameter flow cytometry to measure activation, memory maturation, and multiple functions of total and Ag-specific CD4(+) T cells in 14 HIV-1- and CMV- coinfected individuals at 3 and 12 mo post HIV-1 infection. Primary HIV-1 infection was characterized by elevated levels of CD38, HLA-DR, and Ki67 in total memory and Gag-specific CD4(+) and CD8(+) T cells. In both HIV-infected and 15 uninfected controls, the frequency of activated cells was uniformly distributed among early differentiated (ED; CD45RO(+)CD27(+)), late differentiated (CD45RO(+)CD27(-)), and fully differentiated effector (CD45RO(-)CD27(-)) memory CD4(+) T cells. In HIV-1-infected individuals, activated CD4(+) T cells significantly correlated with viremia at 3 mo postinfection (r = 0.79, p = 0.0007) and also harbored more gag provirus DNA copies than nonactivated cells (p = 0.04). Moreover, Gag-specific ED CD4(+) T cells inversely associated with plasma viral load (r = -0.87, p < 0.0001). Overall, we show that low copy numbers of gag provirus and plasma RNA copies associated with low CD4 activation as well as accumulation of ED HIV-specific CD4(+) memory. Significant positive correlations between 3 and 12 mo activation and memory events highlighted that a steady state of CD4(+) T cell activation and memory maturation was established during primary infection and that these cells were unlikely to be involved in influencing the course of viremia in the first 12 mo of HIV-1 infection.
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Vaginal practices and associations with barrier methods and gel use among Sub-Saharan African women enrolled in an HIV prevention trial.
AIDS Behav
PUBLISHED: 03-31-2010
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Vaginal practices may interfere with the use and/or the effectiveness of female-initiated prevention methods. We investigated whether vaginal practices differed by randomization group in a phase III trial of the diaphragm with lubricant gel (MIRA) in Sub-Saharan Africa (n = 4925), and if they were associated with consistent use of study methods. At baseline, vaginal practices were commonly reported: vaginal washing (82.77%), wiping (56.47%) and insertion of dry or absorbent materials (20.58%). All three practices decreased during the trial. However, women in the intervention group were significantly more likely to report washing or wiping during follow-up compared to those in the control group. Additionally, washing, wiping, and insertion, were all independently and inversely associated with consistent diaphragm and gel use and with condom use as well, regardless of study arm. A better understanding of the socio-cultural context in which these practices are embedded could improve educational strategies to address these potentially modifiable behaviors, and may benefit future HIV prevention interventions of vaginal methods.
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Diaphragm and lubricant gel acceptance, skills and patterns of use among women in an effectiveness trial in Southern Africa.
Eur J Contracept Reprod Health Care
PUBLISHED: 11-26-2009
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We examined diaphragm and gel-related skills, patterns of use, and problems, among women who participated in the MIRA study, a multisite phase III diaphragm trial in Zimbabwe and South Africa.
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The use of the diaphragm instead of condoms in a phase III diaphragm trial.
AIDS Behav
PUBLISHED: 07-14-2009
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The MIRA trial assessed whether providing diaphragm, lubricant gel, and condoms (intervention) compared with condoms alone (control) could reduce HIV incidence among 5,039 Southern African women. Compared with the control group, the cumulative proportion of last sex acts protected by any method was higher in the intervention group (OR = 1.33; 95% CI 1.18, 1.49); however, only 36.3% of last sex acts were protected by both a male condom and a diaphragm, whereas 36.6% were protected by a diaphragm only. Product substitution (ever deciding to use a diaphragm instead of a condom in the previous 3 months) was reported at every visit by 22.4%, at some visits by 60.7%, and at none of the visits by 16.8% of these women. Women at greater risk for infection through their own or their partners behavior or who believed the diaphragm protected against HIV were more likely to report product substitution at every visit.
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Association of HIV-specific and total CD8+ T memory phenotypes in subtype C HIV-1 infection with viral set point.
J. Immunol.
PUBLISHED: 04-04-2009
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Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates of viral control. This study explores the association of differentiation profiles of HIV-specific and total memory CD8(+) T cells with viral set point. A cohort of 47 HIV-1-infected individuals, with differing viral set points at 12 mo, were recruited during acute infection. We identified that the magnitude of IFN-gamma(+) T cell responses at 6 mo postinfection did not associate with viral set point at 12 mo. A subset of 16 individuals was further studied to characterize CD8(+) T cells for expression patterns of markers for memory differentiation, survival (CD127), senescence (CD57), and negative regulation (programmed death-1). We show that viral control and the predicted tempo of HIV disease progression in the first year of infection was associated with a synchronous differentiation of HIV-specific and total CD8(+) memory subpopulations. At 6-9 mo postinfection, those with low viral set points had a significantly higher proportion of early differentiated HIV-specific and total memory CD8(+) cells of a central memory (CD45RO(+)CD27(+)CCR7(+)) and intermediate memory (CD45RO(-)CD27(+)CCR7(-)) phenotype. Those with high viral set points possessed significantly larger frequencies of effector memory (CD45RO(+)CD27(-)CCR7(-)) cells. The proportions of memory subsets significantly correlated with CD38(+)CD8(+) T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8(+) T cells.
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Patterns and predictors of adherence to diaphragm use in a phase III trial in sub-Saharan Africa: a trajectory analysis.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-14-2009
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We examined diaphragm adherence among 2429 women randomized to the intervention arm (diaphragm + gel + condoms) in Methods for Improving Reproductive Health in Africa, a phase III trial of the diaphragm for HIV prevention in Zimbabwe and South Africa.
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Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: results of analyses from a multicenter randomized trial.
BMC Infect. Dis.
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The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries.
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Increased memory differentiation is associated with decreased polyfunctionality for HIV but not for cytomegalovirus-specific CD8+ T cells.
J. Immunol.
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The generation of polyfunctional CD8(+) T cells, in response to vaccination or natural infection, has been associated with improved protective immunity. However, it is unclear whether the maintenance of polyfunctionality is related to particular cellular phenotypic characteristics. To determine whether the cytokine expression profile is linked to the memory differentiation stage, we analyzed the degree of polyfunctionality of HIV-specific CD8(+) T cells within different memory subpopulations in 20 antiretroviral therapy-naive HIV-1-infected individuals at ?34 wk postinfection. These profiles were compared with CMV-specific CD8(+) T cell responses in HIV-uninfected control subjects and in individuals chronically infected with HIV. Our results showed that the polyfunctional abilities of HIV-specific CD8(+) T cells differed according to their memory phenotype. Early-differentiated cells (CD45RO(+)CD27(+)) exhibited a higher proportion of cells positive for three or four functions (p < 0.001), and a lower proportion of monofunctional cells (p < 0.001) compared with terminally differentiated (TD; CD45RO(-)CD27(-)) HIV-specific CD8(+) T cells. The majority of TD HIV-specific CD8(+) T cells were monofunctional (median 69% [interquartile range: 57-83]), producing predominantly CD107a or MIP1?. Moreover, proportions of HIV-specific monofunctional CD8(+) T cells positively associated with proportions of TD HIV-specific CD8(+) T cells (p = 0.019, r = 0.54). In contrast, CMV-specific CD8(+) T cell polyfunctional capacities were similar across all memory subpopulations, with terminally and early-differentiated cells endowed with comparable polyfunctionality. Overall, these data show that the polyfunctional abilities of HIV-specific CD8(+) T cells are influenced by the stage of memory differentiation, which is not the case for CMV-specific responses.
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Quantifying ongoing HIV-1 exposure in HIV-1-serodiscordant couples to identify individuals with potential host resistance to HIV-1.
J. Infect. Dis.
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Immunogenetic correlates of resistance to HIV-1 in HIV-1-exposed seronegative (HESN) individuals with consistently high exposure may inform HIV-1 prevention strategies. We developed a novel approach for quantifying HIV-1 exposure to identify individuals remaining HIV-1 uninfected despite persistent high exposure.
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Increased regression and decreased incidence of human papillomavirus-related cervical lesions among HIV-infected women on HAART.
AIDS
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To determine the impact of HAART on incidence, regression, and progression of cytopathological abnormalities in HIV-infected women.
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Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women.
PLoS ONE
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HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy.
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Specificity of four laboratory approaches for cross-sectional HIV incidence determination: analysis of samples from adults with known nonrecent HIV infection from five African countries.
AIDS Res. Hum. Retroviruses
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Assays to determine cross-sectional HIV incidence misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed factors associated with false-recent misclassification in five African countries. Samples from 2197 adults from Botswana, Kenya, South Africa, Tanzania, and Uganda who were HIV infected > 12 months were tested using the (1) BED capture enzyme immunoassay (BED), (2) avidity assay, (3) BED and avidity assays with higher assay cutoffs (BED+ avidity screen), and (4) multiassay algorithm (MAA) that includes the BED+ avidity screen, CD4 cell count, and HIV viral load. Logistic regression identified factors associated with misclassification. False-recent misclassification rates and 95% confidence intervals were BED alone: 7.6% (6.6, 8.8); avidity assay alone: 3.5% (2.7, 4.3); BED+ avidity screen: 2.2% (1.7, 2.9); and MAA: 1.2% (0.8, 1.8). The misclassification rate for the MAA was significantly lower than the rates for the other three methods (each p < 0.05). Misclassification rates were lower when the analysis was limited to subtype C-endemic countries, with the lowest rate obtained for the MAA [0.8% (0.2, 1.9)]. Factors associated with misclassification were for BED alone: country of origin, antiretroviral treatment (ART), viral load, and CD4 cell count; for avidity assay alone: country of origin; for BED+ avidity screen: country of origin and ART. No factors were associated with misclassification using the MAA. In a multivariate model, these associations remained significant with one exception: the association of ART with misclassification was completely attenuated. A MAA that included CD4 cell count and viral load had lower false-recent misclassification than the BED or avidity assays (alone or in combination). Studies are underway to compare the sensitivity of these methods for detection of recent HIV infection.
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Determinants of per-coital-act HIV-1 infectivity among African HIV-1-serodiscordant couples.
J. Infect. Dis.
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Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 (HIV-1) is important for designing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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