All requests for initiating new sub-studies or for collaborative research projects within the WIHS must first be submitted in the form of a concept sheet. Once approved by the Executive Committee, new initiatives and protocol changes are generally instituted at the start of a visit cycle. Contact the local WIHS Site at UAB or UMMC if you are interested in submitting a concept study form to WIHS for guidance and assistance.


Areas of Focused Scientific Research In WIHS

Behavior & Substance Use                 Cancer                                    Menopause & Aging

Metabolics & Renal Disease                Epidemiology                        Cardiovascular Disease

                      Neurocognition                                    Genetics                                Pharmacokinetics/HARRT Exposure

Hepatitis & Live Disease                     Pathogenesis                        Human Papillomavirus




WIHS Publications & Acknowledgements


ACKNOWLEDGE THE WIHS:
The NIH grants policy requires researchers to acknowledge federal funding when issuing publications, scientific presentations, press releases, and other products describing projects or programs funded in whole or in part with federal money. Receiving a research grant from the NIH obligates you to inform the public that your research is being funded by taxpayer dollars.

Please acknowledge the UAB-UMMC WIHS Site funding with similar wording: This research was supported by the Women’s Interagency HIV Study, an NIH funded program (U01AI103401) that was made possible by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA) and the National Cancer Institute (NCI).

                                                                     RSS FEED of UAB-UMMC SITE PUBLICATIONS:
WIHS Publications from the UAB-UMMC Site are regularly updated by Pubmed RSS feed on the Homepage

SYNOPSIS OF NATIONAL WIHS PUBLICATIONS AND MILESTONES SINCE COHORT INCEPTION:

1993: Early WIHS publications were able to describe gender specific issues regarding HIV clinical outcomes and disease management. (Anastos, Yale Univ Press 1993)

1994: The strong association between drug use and HIV was demonstrated in the WIHS cohort. One third of the Brooklyn, NY cohort used crack cocaine and just 22% reported using a condom at last sexual contact. Cocaine users were about 3 times more likely to have undiagnosed STDs. (Dehovitz AJE 1994)

1995: Women with HIV infection, particularly those with low CD4 cell counts, were 4.1 fold more likely to shed genital herpes simplex virus type 2 (HSV-2) from the vulva and cervix than HIV-negative women (Augenbraun Ann Int Med 1995)

1996 Still early in its establishment as a cohort study, WIHS was already contributing key data on care guidelines for women. (Anastos Raven Press 1996)

1997: Previously studies of HHV8 among men who have sex with men, found prevalence rates over 30%. A study in WIHS found that HIV positive women had higher HHV8 prevalence ant 4% than HIV negative women 1.2%. These much lower levels explaining the low prevalence of KS among women. (Kedes JAMA 1997)

1998: Condom use was higher among HIV positive women, but still low at 65%. Increased use of crack cocaine was positively associated with STI disease among women (Wilson STD 1998) (relative risk [RR] = 1.23, P < .01).

1999: WIHS publishes research on the prevalence of gynecologic disease (Minkhoff AJOB 1999) and the role of vaginosis-associated microflora activation on HIV-1 increased expression. (AlHarthi JAIDS 1999). The close association of HIV viral load and CD4 cell response was also demonstrated for women in WIHS (Anastos AIDS 1999)

2000: WIHS shows relationship of gender, race and other factors to HIV progression and death (Anastos JAIDS 2000; Feldman AIDS 2000); Two-thirds of HIV-positive women are found to be former or current victims of domestic violence (Cohen AJPH 2000)

2001: WIHS shows that HIV-positive or at risk women, predominantly black, can be recruited and retained in prospective studies (Hessol AJE 2001); HIV viral shedding in the genital tract is found to persist even among women with low viral loads (Kovacs Lancet 2001); HIV-HPV co-infections and low CD4+ counts linked to abnormal anal cytology (Palefsky JID 2001; Holly PNAS 2001).

2002: Studies show 20% of deaths among HIV-positive women due to non-AIDS causes (Cohen AJM 2002) and that women with T-cell counts of 200-350/µL are not at greater risk of death than those with higher counts (Anastos AIM 2002); depression is common among HIV-positive women and strongly linked to poor adherence to ARV regimes (Cook JAIDS 2002).

2003: WIHS develops advanced statistical methods to analyze observational data (Cole AJE 2003); finds that peripheral and central lipoatrophy (fat loss) is 2-fold more frequent among HIV-positive than –negative women (Tien JAIDS 2003); genital tract and plasma found to harbor distinct HIV-1 viral strains(Kemal PNAS 2003). Research on HPV-16 finds it is least associated with HIV immune suppression suggesting this virus, as compared to other HV strains, is uniquely able to avoid immune responses. (Strickler J NCI 2003). Repository based lab research found that hsCRP was elevated in HIV as compared to HIV negative women.

2004 Several HIV mortality studies were published this year: showing HIV-positive women to be at increased risk of death from kidney disease (Szczech CID 2004); WIHS found post-HAART CD4 predicted survival more than pre-HAART levels (Anastos Ann Intern Med. 2004) Further research showed, using inverse probability weighting, a 1.79 times increased risk of death for those who stopped ARV. (Barron, AIDS 2004) Viral sequence research demonstrated super-infection and viral recombination. WIHS showed that HAART use was safe for use in women with HCV. (French Clin Infect Dis 2004). Women had decreased oral manifestations of disease (Greenspan J Dent Res 2004). However, cancer rates were increased nearly two fold overall higher for HIV related cancers. (Hessol JAIDS 2004). Behavioral interviews found condom use dropped for women on ARVs. (Wilson, AJPH 2004)

2005 WIHS continued to demonstrate racial disparities in care with AA women achieving equivalent virologic, immunologic, or clinical outcomes only after adjustment for continued HAART use and depression. (Anastos JAIDS 2005) Therapy discontinuation was common in 2005, and WIHS demonstrated that depression was a strong predictor. (Ahdieh JAIDS 2005) The importance of WIHS research was highlighted in a paper that demonstrated that on average 42% of women in WIHS would have been excluded from clinical trials based on the reported exclusion criteria. In a combined cohort analysis WIHS and MACS showed that HAART had profoundly improved survival after AIDS. Importantly, AIDS was no longer an indicator of certain mortality, but was survivable for a majority of patients, with only 25% of patients dying within 5 years of an AIDS diagnosis.

2006: Neutropenia was common among HIV-positive women with about 44% having counts under 2000/µl and 7% under 1000/µl. It was significantly associated with lower CD4+ counts (<.001) and higher HIV viral loads (<.001) and resolved with use of HAART (p=.007), but not linked to survival (Levine AIM 2006).

2007: While overall rates of diabetes did not differ for HIV + versus HIV- women, among HIV+ women those NRTI therapy for 0-3 years and >3 years were at 1.8-fold and 2.64 fold greater risk of diabetes compared to those with no NRTI exposure respectively (Tien AIDS 2007). WIHS studies of lypodystrophy revealed the risk peripheral wasting for those on stavudine which stabilized only 2 years after discontinuation of the medication. (Tien, JAIDS, 2007) In a collaborative study with MACS and ALIVE, WIHS researchers found that IDU was not a risk factor for discontinuation of ARVs, and instead low SES, unemployment and minority race were key predictors (Morris AIDS Research therapy, 2007). Increased attention was directed at cardiovascular risk factors, WIHS demonstrated that hypertension was not increased among HIV+ women as compared to HIV- (26% vs 28%) and while traditional risk factors were predictors of risk, HIV status, CD4 and viral load were not (Khalsa,. AIDS) Women who believed ARVs were effective demonstrated behavioral disinhibition reporting lower condom usage (54% versus 63%) (Wilson, AIDS Educ and Prevention, 2007)

2008: X-4 viruses predicted outcomes for women on ARVs and could be used as a clinically important risk factor. (Weiser, AIDS) Further work highlighted the risk of insulin resistance among women taking an NRTI, particularly stavudine. (Tien JAIDS) Women using complementary and alternative medicines were more likely to initiate HAART. (Merenstein, Altern Ther Health Med) Because WIHS follows both HIV- and HIV+ women, researchers could evaluate the independent contributions of HIV status, and therapy on clinical outcomes. Body habitus (Justman JAIDS) and CVD risk studies were performed. A two-fold increased risk of carotid lesions in HIV+ women as compared to HIV – women was found (Kaplan, AIDS). The cohorts continued to be a platform for novel statistical research in inverse probability weighting. (Cole, AJE)

2009: WIHS research on aging-related frailty found that while women with CD4 cell counts <100 were 2.7 times more likely to be frail as HIV- women but those with CD4 counts > 100 had similar prevalence of frailty to HIV- women (Terzian, J Women's Health) further virology work continued to document super infection and recombination in the US. WIHS continued to maintain outstanding follow-up of participants with 86% of the women enrolled in 2001 still in the study. (Hessol J Women's Health). Capitalizing on the infrastructure in WIHS, research to study pharmacology of ARVs in women was performed defining risk factors for high and lower than expected drug levels (Ghandi, JAIDS). WIHS also developed hair assays to give long-term therapy exposure data. (Ghandi, AIDS) WIHS documented a decline in deaths from a high of 24.7 in 1996 to a plateau of 10.1 in 2001-2004. The most common causes of death were: trauma or overdose, liver disease, cardiovascular disease, and malignancy, with depression and hepatitis B or C infection as the strongest predictors of death (French, JAIDS)

2010: WIHS continued to be a leader in statistical analysis with the use of alternative time scales (Westreich AJE) Detailed cardiovascular studies found that distensibility in HIV+ women was reduced by 4.3% as compared to HIV- women, for those with CD<200 distensibility was 10.5% lower. (Seaberg Stroke). MACS and WIHS longitudinal cohorts with reposited samples were able to demonstrate that hsCRP increased and d-dimer and IL-6 levels decrease when patients started HAART, but that these changes were not unique to Abacavir (Palella AIDS). WIHS continued to study Hepatitis co-infection and found genetic markers for clearance (Kuniholm, Hepatology) and that non-invasive markers could be used to measure liver steatosis (Ghtob JAIDS). Novel economic analysis using instrumental variables showed that use of anti-depressives improved employment by 29%. (Galárraga Health Econ). Kidney disease was also a focus of research, finding a 1.89 fold increased risk of death for women with chronic kidney disease after adjusting for age, race, hepatitis C serostatus, AIDS history, CD4 cell count, hypertension and diabetes history. (Estrella, JAIDS)

2011: WIHS works with investigators from other North American cohorts to study HIV resistance, finding that that trends in HIV drug resistance among patients in care that were markedly different from those observed using only data from patients who had undergone genotype tests (Abraham AJE). The innovative research conducted in WIHS using forensic methods to measure ARV exposure in hair shows that WIHS subjects in the highest category hair levels of atazanavir are 60-fold more likely to be viral suppressed than those in the lowest category, the most predictive variable in statistical models (Gandhi Clin Inf Dis). Two CVD studies are published showing that HIV-associated subclinical carotid artery abnormalities are elevated even among HIV+ women receiving ARV therapy (Kaplan J Inf Dis) and that higher viral loads are associated with decreased carotid artery distensibility, suggesting that pro-inflamatory populations of T-cells may produce functional or structural vascular changes in HIV+ women (Kaplan, Atherosclerosis). HIV+ women are found to score significantly lower than HIV-negative women on a measure of neurocognitive function (Manly, J Clin Exp Neuropsychol).

2012: WIHS uses American Recovery and Reinvestment Act (ARRA) funds to conduct a 5 million SNP panel genome-wide association study (GWAS) of the entire cohort; a 2012 study shows that HIV+ women with the CYP2B6 516TT genotype have 3-fold increases in both short-term and long-term efavirenz exposure (Gandhi, JID). After a negative baseline Pap test, 1% of HIV+ women are found to develop precancer within 15 months and 4% within 15-39 months, suggesting that annual Pap tests are safe for HIV+ women (Massad, Obstet Gyn). Women co-infected with HIV and HCV who have elevations on two liver function tests are found to be at 2.6-fold (FIB4) and 2.8-fold (APRI) greater risk of death within 5 years, compared to co-infected women with low levels (Bambha, AIDS). Just 30% of WIHS subjects report using pharmacist counseling to resolve medication-related issues within the last 6 months, suggesting that pharmacist medication counseling services in the US are underutilized, negatively affecting ARV adherence (Cocohoba Pat Pref and Adherence). A study of WIHS data included with other North American cohort data shows that anal cancer rates are substantially higher for HIV-infected men and women compared to HIV-negative patients (Silverberg CID). Studies of HIV-HCV co-infected WIHS subjects show that black women are about 40% less likely than white and Hispanic women to clear HCV (Sarkar, Dig Dis Sci).

2013: Further studies of HIV/HCV co-infected WIHS subjects show that IL28B and HLA class II genes are independently associated with spontaneous resolution of HCV and that blacks are less likely to have the advantageous genotype (Duggal Ann Int Med); but that in spite of this genetic disadvantage, black women in WIHS co-infected with HIV and HCV are about 60% less likely to die liver-related deaths than similarly infected white women (Sarkar Hepatology). Among black women in WIHS, 89% are found to have insufficient vitamin D levels (Aziz AIDS), an insufficiency found to be significantly associated with lower odds of CD4 recovery and undetectable viral loads after HAART initiation (Aziz AIDS). Vitamin D insufficiency was marginally associated (OR = 1.8) with higher homeostasis model assessment (HOMA) values and insulin resistance (Adeyemi AIDS Pat Care STDS).

Investigator Guidelines


The WIHS calendar is based on two-six month visit cycles per year, October 1st – March 31st and April 1st – September 30th. All requests for initiating new sub-studies or for collaborative research projects within the WIHS must first be submitted in the form of a concept sheet. Once approved by the Executive Committee, new initiatives and protocol changes are generally instituted at the start of a visit cycle.

IRB - Each site within each consortium must obtain their own institution's IRB approval prior to initiating new projects or significant changes in the protocol and all staff that will be involved will require appropriate orientation and/or training to carry out new protocols. In 2000, in addition to the core protocol, there was an initiative to revamp and re-prioritize one facet of the protocol, there were six national sub-studies and three collaborating RO1s, and multiple local, site-specific sub-studies being conducted within the WIHS.

Given the size of the WIHS structure and the volume of research being conducted, all investigators who are bringing new projects to the WIHS will need to consider three elements: time, communication, teamwork.

TIME – No one sub-study can take precedence. To get application paperwork from the consortia, or to organize a newly approved project, you will cue up behind others already in process – so start early. Notify WIHS Project Directors (PDs) well in advance of any due dates and be specific regarding your needs and time-table. Negotiation of the budget must be completed with each site before grant submission, and as soon as funding is approved or cuts are required, contact sites. You may contact each site directly, or start by contacting the Chair of the Project Directors' Group. This is a rotating position, so check with the local WIHS contact to find out who is currently PD Chair.

COMMUNICATION – Organize your information into a comprehensive request. For example, if you are applying for a new grant, you may need the following: investigator biographies, other support information, certification of human subjects protection training, investigators' disclosure of financial interest, institutional agreement to participate, budgets, etc... A flurry of individual requests causes confusion and items are likely to be overlooked. Send requests to the PDs via electronic mail. Direct your data requests to the PD at WIHS Data Management and Analysis Center (WDMAC).

TEAMWORK – Each consortium within the WIHS has unique aspects to its organization and the requirements for carrying out additional projects may vary. The PD is intimately aware of the resources, organization, and limitations of her specific WIHS consortium. WIHS PDs are also experienced in organizing and coordinating multi-center studies. However, you must keep in mind that the WIHS consortia have limited administrative staff and while they can provide you with the information you request – you may have to be responsible for formatting some items to meet your needs. Once funded, you will be responsible for the bulk of the work required in organizing the protocol and developing data forms and consent templates. These should be reviewed by your local WIHS PD prior to submission to WDMAC. These forms are needed for IRB submission so must be distributed at least two months before you anticipate starting enrollment. As with the core study and all sub-studies of the WIHS, the PDs are happy to work with the investigator in a team effort to make your research a success and hope you will draw on their resources early in the process.

Submit a Concept


The WIHS calendar is based on two-six month visit cycles per year, October 1st – March 31st and April 1st – September 30th. All requests for initiating new sub-studies or for collaborative research projects within the WIHS must first be submitted in the form of a concept sheet. The WIHS concept sheet can be downloaded at the WIHS national site under Investigator Information.  Once approved by the Executive Committee, new initiatives and protocol changes are generally instituted at the start of a visit cycle.

IRB - Each site within each consortium must obtain their own institution's IRB approval prior to initiating new projects or significant changes in the protocol and all staff that will be involved will require appropriate orientation and/or training to carry out new protocols. In 2000, in addition to the core protocol, there was an initiative to revamp and re-prioritize one facet of the protocol, there were six national sub-studies and three collaborating RO1s, and multiple local, site-specific sub-studies being conducted within the WIHS.

SPECIMEN SELECTION - Many factors contribute to specimen selection such as the focus of the laboratory assay, serostatus requirements, HAART status, rate of disease progression, and whether progression should be defined clinically or immunologically. Investigators should consider all relevant selection criteria prior to sending sample specifications to the WIHS Data Management and Analysis Center (WDMAC).

All specimen requests should be handled according to the WIHS policies and procedures for such requests. Check the WIHS national website for specific guidelines and forms. Requests are submitted to the WDMAC Project Director, Christine Alden (calden@jhsph.edu).

Requests for specimens will not be processed until the science is approved by the WIHS Executive Committee (EC) and verification of local IRB approval has been granted. Requests should include a completed repository checklist, which can be found on the WIHS Public Website. If the investigator has already determined WIHSID-visits, an Excel spreadsheet of WIHSIDs, visits and visit dates should be attached to the request. If the investigator has not yet determined WIHSID-visits, a WDMAC programmer will work with the investigator to select appropriate WIHSID-visits based on the selection criteria in the approved concept sheet. The WIHS Repository Checklist must be filled out in full so the WIHS Project Director can properly process the request and determine if a WIHS Statistical Programmer is needed.

Please note that times from request to shipment may vary depending upon results of QA process, workload at WDMAC and SeraCare, and availability of specimens at SeraCare, but WDMAC strives to submit all requests to the repository within one week of QA completion. SeraCare will ship the specimens within 5 weeks (8 weeks if the specimens need relabeling) of request submission.

REQUEST TO WIHS Data Management and Analysis Center (WDMAC)

The WIHS Repository Request Checklist includes:
  • The Readme number for the project;
  • Investigator contact and email information;
  • Specimen Type;
  • Total expected number of specimens;
  • Minimum acceptable volume;
  • Lab that specimens should be shipped to, including name, address and at least one phone number;
  • Freeze/thaw info – preferred method of shipping (dry ice, liquid nitrogen); whether or not pristine specimens are required; if SeraCare should thaw and aliquot;
  • Special instructions: Should the repository pack vials for shipment in any particular order? Does the project require blinded/relabeled specimens? What variables will the testing facility need on the manifest from the repository? What is an acceptable file format for the manifest so that the testing facility can incorporate the file into their tracking system?
  • Signed assurance that the project has local IRB approval.
Fax the completed checklist to Christine Alden at 410-223-1666

RESTRICTIONS ON SAMPLES

When an investigator unknowingly requests the last vial for a WIHSID-visit-specimen, WIHS Data Management and Analysis Center (WDMAC) will inform the investigator, asking him or her to select alternate visits or WIHSIDs from which another vial may be taken. If this is not possible, the investigator should contact local repositories for the needed specimens. If no alternates are available, then the investigator may request additional review by the WIHS EC to justify the scientific use of those specimens. Only the WIHS EC can approve the release of the last vial of a specimen type, WIHSID, visit unique combination.

The B-cell immortalization program was ended in July of 2004. 60% of WIHS participants have
established B-cell lines (73% of the 94/95 cohort and 29% of the 01/02 cohort). Only cell pellets can be distributed to investigators. Requests for immortalized samples should follow the process described above.

GENERAL GUIDELINES

The WIHS Investigators are providing the specimens with the understanding that the WIHS is entering into a full collaboration with the individual study investigator(s) and that all data generated from the WIHS specimens will be provided to the WIHS EC (or WDMAC) in a timely fashion as outlined below. Moreover, the data generated from WIHS specimens will remain the property of the WIHS EC, but the study investigator(s) will have exclusive first rights to the publication of these data as outlined below.

All data generated from the WIHS specimens must be submitted to WIHS Data Management and Analysis Center (WDMAC) at the earliest of the following:
  • 1 month following the acceptance of the first paper to be written using the WIHS data.
  • 1 year following the receipt of the WIHS specimens by the study investigator.

The deadlines specified above are open to negotiation with the WIHS EC. They may be altered only by the WIHS EC with alternate deadlines being specified in a letter drafted by the WIHS EC and addressed to the study investigator.

To ensure that progress is being made on the testing of WIHS specimens, quarterly updates detailing the status of the testing of the specimens and the preparation of the manuscript must be submitted to the WIHS EC beginning 3 months after the receipt of the specimens by the study investigator. If the specimens have not been tested within 1 year of receipt, then the specimens must be returned to the WIHS.

REQUIREMENTS OF RESULT DATASET

The results dataset should be sent via email to the WIHS Data Management and Analysis Center (WDMAC) Data Manager with the WIHS readme number, a brief synopsis of the project and type of testing performed. Investigators are also responsible for sending a codebook that includes valid result ranges and full test names. If the results are published at the time of dataset transmission, the investigator should also send a complete citation.

The dataset can be in excel or ASCII format. At a minimum, the dataset should include the following variables for each record: WIHSID, visit, specimen collection date, specimen testing date, test(s), and result(s).

National WIHS Site


Click here to visit the National WIHS Website