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Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation.
Pettit AC, Giganti MJ, Ingle SM, May MT, Shepherd BE, Gill MJ, Fätkenheuer G, Abgrall S, Saag MS, Del Amo J, Justice AC, Miro JM, Cavasinni M, Dabis F, Monforte AD, Reiss P, Guest J, Moore D, Shepherd L, Obel N, Crane HM, Smith C, Teira R, Zangerle R, Sterne JA, Sterling TR, Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators
(2018) J Int AIDS Soc 21:
MeSH Terms: Acquired Immunodeficiency Syndrome, Adult, Anti-HIV Agents, Cohort Studies, Female, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Pneumonia, Pneumocystis, Tuberculosis
Show Abstract · Added March 14, 2018
INTRODUCTION - HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation.
METHODS - We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.
RESULTS - The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).
CONCLUSIONS - In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.
© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.
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11 MeSH Terms
Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge.
Julg B, Tartaglia LJ, Keele BF, Wagh K, Pegu A, Sok D, Abbink P, Schmidt SD, Wang K, Chen X, Joyce MG, Georgiev IS, Choe M, Kwong PD, Doria-Rose NA, Le K, Louder MK, Bailer RT, Moore PL, Korber B, Seaman MS, Abdool Karim SS, Morris L, Koup RA, Mascola JR, Burton DR, Barouch DH
(2017) Sci Transl Med 9:
MeSH Terms: Amino Acid Sequence, Animals, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, Female, HIV Envelope Protein gp120, HIV-1, Macaca mulatta, Male, Neutralization Tests, Sequence Alignment, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Viral Load
Show Abstract · Added March 14, 2018
Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific neutralizing antibodies. We created a novel SHIV-325c viral stock that included a clade C HIV-1 envelope and was susceptible to neutralization by both of these antibodies. Rhesus macaques received a single infusion of either antibody at three different concentrations (2, 0.4, and 0.08 mg/kg) before challenge with SHIV-325c. PGDM1400 was fully protective at the 0.4 mg/kg dose, whereas CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose, which correlated with its greater in vitro neutralization potency against the challenge virus. Serum antibody concentrations required for protection were <0.75 μg/ml for CAP256-VRC26.25-LS. These data demonstrate unprecedented potency and protective efficacy of V2-specific neutralizing antibodies in nonhuman primates and validate V2 as a potential target for the prevention of HIV-1 infection in passive immunization strategies in humans.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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14 MeSH Terms
Re-validation of the Van Rie HIV/AIDS-related stigma scale for use with people living with HIV in the United States.
Kipp AM, Audet CM, Earnshaw VA, Owens J, McGowan CC, Wallston KA
(2015) PLoS One 10: e0118836
MeSH Terms: Acquired Immunodeficiency Syndrome, Female, Health, Humans, Male, Middle Aged, Psychometrics, Social Stigma, Surveys and Questionnaires, United States
Show Abstract · Added July 28, 2015
There is little consensus about which of the many validated human immunodeficiency virus (HIV) stigma scales should be regularly used, with few being re-validated in different contexts or evaluated for how they compare to other, existing HIV stigma scales. The purpose of this exploratory study was to re-validate the Van Rie HIV/AIDS-Related Stigma Scale, originally validated in Thailand and using a third-person wording structure, for use with people living with HIV in the United States. Adult HIV clinic patients completed a survey including the Berger and Van Rie scales, and measures of social support and depression. Eighty-five of 211 (40%) eligible participants provided data for both stigma scales. Exploratory factor analyses identified three factors to the Van Rie scale: Loss of Social Relationships (new subscale), Managing HIV Concealment (new subscale), and Perceived Community Stigma (original subscale). These subscales were moderately inter-related (r = 0.51 to 0.58) with acceptable to excellent reliability (Cronbach's alpha = 0.69 to 0.90). The Van Rie subscales were also moderately inter-correlated with the Berger subscales (r = 0.44 to 0.76), had similar construct validity, and tended to have higher mean stigma scores when compared with Berger subscales that were conceptually most similar. The revised Van Rie HIV-related Stigma Scale demonstrates good validity and internal consistency, offering a valid measure of HIV stigma with a three-factor structure. The third-person wording may be particularly suitable for measuring stigmatizing attitudes during an individual's transition from at-risk and undergoing HIV testing to newly diagnosed, a time when experiences of discrimination and processing issues of disclosure have not yet occurred. The stigma mechanisms for individuals making this transition have not been well explored. These scenarios, combined with the observed non-response to the Berger Enacted Stigma subscale items (a surprise finding), highlight gaps in our understanding of HIV stigma and how best to measure it.
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10 MeSH Terms
Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.
Lehmann DS, Ribaudo HJ, Daar ES, Gulick RM, Haubrich RH, Robbins GK, de Bakker PI, Haas DW, McLaren PJ
(2015) Pharmacogenet Genomics 25: 51-9
MeSH Terms: Acquired Immunodeficiency Syndrome, Anti-HIV Agents, Benzoxazines, Dideoxynucleosides, Drug Therapy, Combination, Genome-Wide Association Study, HIV Infections, HIV-1, Humans, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Treatment Outcome
Show Abstract · Added March 13, 2015
BACKGROUND - Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols.
PARTICIPANTS AND METHODS - Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n = 786) regimens in ACTG protocols 384, A5142, A5095, and A5202.
RESULTS - Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P < 5 × 10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition.
CONCLUSION - No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.
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12 MeSH Terms
Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants.
Frey SE, Peiperl L, McElrath MJ, Kalams S, Goepfert PA, Keefer MC, Baden LR, Lally MA, Mayer K, Blattner WA, Harro CD, Hammer SM, Gorse GJ, Hural J, Tomaras GD, Levy Y, Gilbert P, deCamp A, Russell ND, Elizaga M, Allen M, Corey L
(2014) Clin Vaccine Immunol 21: 1589-99
MeSH Terms: AIDS Vaccines, Acquired Immunodeficiency Syndrome, Adolescent, Adult, Drug-Related Side Effects and Adverse Reactions, Enzyme-Linked Immunosorbent Assay, Enzyme-Linked Immunospot Assay, Female, HIV Antibodies, HIV-1, Humans, Interferon-gamma, Male, Middle Aged, Placebos, Treatment Outcome, Vaccination, Young Adult
Show Abstract · Added January 20, 2015
Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 μg), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV (vCP1452) followed by ALVAC-HIV (vCP1452) plus LIPO-5 (250, 750, and 2,500 μg). Only 73/174 participants (42%) received all four vaccinations due to a study halt related to myelitis. There were no significant differences in systemic reactions between groups or in local reactogenicity between groups receiving ALVAC-HIV (vCP1452). Significant differences in local reactogenicity occurred between groups receiving LIPO-5 (P ≤ 0.05). Gag and Env antibodies were undetectable by ELISA 2 weeks after the fourth vaccination for all but one recipient. Antibodies to Gag and Env were present in 32% and 24% of recipients of ALVAC-HIV (vCP1452) alone and in 47% and 35% of ALVAC-HIV (vCP1452)+LIPO recipients, respectively. Coadministration of LIPO-5 did not significantly increase the response rate compared to ALVAC-HIV (vCP1452) alone, nor was there a significant relationship between dose and antibody responses among ALVAC-HIV (vCP1452)+LIPO groups. Over 90% of study participants had no positive gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses to any peptide pool at any time point. The study was halted due to a case of myelitis possibly related to the LIPO-5 vaccine; this case of myelitis remains an isolated event. In general, there was no appreciable cell-mediated immunity detected in response to the vaccines used in this study, and antibody responses were limited. The clinical trial is registered on ClinicalTrials.gov with registry number NCT00076063.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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18 MeSH Terms
Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202.
Johnson DH, Venuto C, Ritchie MD, Morse GD, Daar ES, McLaren PJ, Haas DW
(2014) Pharmacogenet Genomics 24: 195-203
MeSH Terms: Acquired Immunodeficiency Syndrome, Adult, Antiretroviral Therapy, Highly Active, Atazanavir Sulfate, Bilirubin, Female, Genome-Wide Association Study, Glucuronosyltransferase, HIV Protease Inhibitors, Humans, Hyperbilirubinemia, Male, Middle Aged, Multivariate Analysis, Oligopeptides, Polymorphism, Single Nucleotide, Prospective Studies, Pyridines, Ritonavir
Show Abstract · Added March 13, 2015
BACKGROUND - Atazanavir-associated hyperbilirubinemia can cause premature discontinuation of atazanavir and avoidance of its initial prescription. We used genomewide genotyping and clinical data to characterize determinants of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202.
METHODS - Plasma atazanavir pharmacokinetics and indirect bilirubin concentrations were characterized in HIV-1-infected patients randomized to atazanavir/ritonavir-containing regimens. A subset had genomewide genotype data available.
RESULTS - Genomewide assay data were available from 542 participants, of whom 475 also had data on estimated atazanavir clearance and relevant covariates available. Peak bilirubin concentration and relevant covariates were available for 443 participants. By multivariate analysis, higher peak on-treatment bilirubin levels were found to be associated with the UGT1A1 rs887829 T allele (P=6.4×10(-12)), higher baseline hemoglobin levels (P=4.9×10(-13)), higher baseline bilirubin levels (P=6.7×10(-12)), and slower plasma atazanavir clearance (P=8.6×10(-11)). For peak bilirubin levels greater than 3.0 mg/dl, the positive predictive value of a baseline bilirubin level of 0.5 mg/dl or higher with hemoglobin concentrations of 14 g/dl or higher was 0.51, which increased to 0.85 with rs887829 TT homozygosity. For peak bilirubin levels of 3.0 mg/dl or lower, the positive predictive value of a baseline bilirubin level less than 0.5 mg/dl with a hemoglobin concentration less than 14 g/dl was 0.91, which increased to 0.96 with rs887829 CC homozygosity. No polymorphism predicted atazanavir pharmacokinetics at genomewide significance.
CONCLUSION - Atazanavir-associated hyperbilirubinemia is best predicted by considering UGT1A1 genotype, baseline bilirubin level, and baseline hemoglobin level in combination. Use of ritonavir as a pharmacokinetic enhancer may have abrogated genetic associations with atazanavir pharmacokinetics.
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Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
Leger PD, Johnson DH, Robbins GK, Shafer RW, Clifford DB, Li J, McLaren PJ, Haas DW
(2014) J Neurovirol 20: 304-8
MeSH Terms: Acquired Immunodeficiency Syndrome, Anti-HIV Agents, Case-Control Studies, Drug Combinations, Drug Therapy, Combination, Genome-Wide Association Study, Genotype, Humans, Lamivudine, Multicenter Studies as Topic, Peripheral Nervous System Diseases, Polymorphism, Genetic, Principal Component Analysis, Randomized Controlled Trials as Topic, Retrospective Studies, Stavudine, Treatment Outcome, Zidovudine
Show Abstract · Added March 13, 2015
Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect.
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Association between U.S. state AIDS Drug Assistance Program (ADAP) features and HIV antiretroviral therapy initiation, 2001-2009.
Hanna DB, Buchacz K, Gebo KA, Hessol NA, Horberg MA, Jacobson LP, Kirk GD, Kitahata MM, Korthuis PT, Moore RD, Napravnik S, Patel P, Silverberg MJ, Sterling TR, Willig JH, Collier A, Samji H, Thorne JE, Althoff KN, Martin JN, Rodriguez B, Stuart EA, Gange SJ, North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
(2013) PLoS One 8: e78952
MeSH Terms: Acquired Immunodeficiency Syndrome, Anti-Retroviral Agents, Canada, Female, Government Programs, Healthcare Financing, Humans, Male, Retrospective Studies, United States
Show Abstract · Added May 29, 2014
BACKGROUND - U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
METHODS - We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU).
RESULTS - Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60-0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87-1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47-0.95).
CONCLUSIONS - We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.
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10 MeSH Terms
Improving diagnostic capability for HPV disease internationally within the NIH-NIAID Division of AIDS Clinical Trial Networks.
Godfrey CC, Michelow PM, Godard M, Sahasrabuddhe VV, Darden J, Firnhaber CS, Wetherall NT, Bremer J, Coombs RW, Wilkin T, A5282 Study Team
(2013) Am J Clin Pathol 140: 881-9
MeSH Terms: Acquired Immunodeficiency Syndrome, Clinical Trials, Phase II as Topic, Female, Human Papillomavirus DNA Tests, Humans, Laboratories, Mass Screening, National Institutes of Health (U.S.), Papillomavirus Infections, Pathology, Quality Assurance, Health Care, Randomized Controlled Trials as Topic, United States, Uterine Cervical Neoplasms
Show Abstract · Added March 5, 2014
OBJECTIVES - To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network.
METHODS - A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit.
RESULTS - Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested.
CONCLUSIONS - The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement.
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14 MeSH Terms
Utilization of cervical cancer screening services and trends in screening positivity rates in a 'screen-and-treat' program integrated with HIV/AIDS care in Zambia.
Mwanahamuntu MH, Sahasrabuddhe VV, Blevins M, Kapambwe S, Shepherd BE, Chibwesha C, Pfaendler KS, Mkumba G, Vwalika B, Hicks ML, Vermund SH, Stringer JS, Parham GP
(2013) PLoS One 8: e74607
MeSH Terms: Acquired Immunodeficiency Syndrome, Adult, Demography, Early Detection of Cancer, Female, HIV Seropositivity, Humans, Logistic Models, Multivariate Analysis, Probability, Uterine Cervical Neoplasms, Zambia
Show Abstract · Added March 5, 2014
BACKGROUND - In the absence of stand-alone infrastructures for delivering cervical cancer screening services, efforts are underway in sub-Saharan Africa to dovetail screening with ongoing vertical health initiatives like HIV/AIDS care programs. Yet, evidence demonstrating the utilization of cervical cancer prevention services in such integrated programs by women of the general population is lacking.
METHODS - We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia (CCPPZ), the largest public sector programs of its kind in sub-Saharan Africa. We evaluated patterns of utilization of screening services by HIV serostatus, examined contemporaneous trends in screening outcomes, and used multivariable modeling to identify factors associated with screening test positivity.
RESULTS - Between January 2006 and April 2011, CCPPZ services were utilized by 56,247 women who underwent cervical cancer screening with visual inspection with acetic acid (VIA), aided by digital cervicography. The proportion of women accessing these services who were HIV-seropositive declined from 54% to 23% between 2006-2010, which coincided with increasing proportions of HIV-seronegative women (from 22% to 38%) and women whose HIV serostatus was unknown (from 24% to 39%) (all p-for trend<0.001). The rates of VIA screening positivity declined from 47% to 17% during the same period (p-for trend <0.001), and this decline was consistent across all HIV serostatus categories. After adjusting for demographic and sexual/reproductive factors, HIV-seropositive women were more than twice as likely (Odds ratio 2.62, 95% CI 2.49, 2.76) to screen VIA-positive than HIV-seronegative women.
CONCLUSIONS - This is the first 'real world' demonstration in a public sector implementation program in a sub-Saharan African setting that with successful program scale-up efforts, nurse-led cervical cancer screening programs targeting women with HIV can expand and serve all women, regardless of HIV serostatus. Screening program performance can improve with adequate emphasis on training, quality control, and telemedicine-support for nurse-providers in clinical decision making.
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12 MeSH Terms