Joelle Brown | University of California, San Francisco (original) (raw)

Papers by Joelle Brown

Objectives—To determine if healthy, young women in sub-Saharan Africa have a more activated immun... more Objectives—To determine if healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4+ T-cells) than a similar population in the US.

Journal of the International AIDS Society, 2015

Safer conception strategies (SCS) have the potential to decrease HIV transmission among HIV-disco... more Safer conception strategies (SCS) have the potential to decrease HIV transmission among HIV-discordant couples who desire children. Community perceptions of SCS may influence the scale-up and uptake of these services, but little is known about how communities will react to these strategies. Without community support for SCS, their success as an HIV prevention tool may be limited. The objective of this study is to characterize community perceptions of SCS for HIV-discordant couples in Kisumu, Kenya, to inform ongoing and future safer conception intervention studies in low-resource settings. We conducted six focus group discussions and 11 in-depth-interviews in Kisumu, Kenya, among a diverse group (N=59) of community members, including men, women, youth (age 19-25), community health workers and local leaders. An iterative qualitative analysis using a grounded theory approach was employed. All participants emphasized the importance of childbearing in their society and the right to have children, regardless of an individual's HIV status. While most participants believed that HIV-discordant couples should be allowed to have children, they discussed several barriers to the uptake of SCS such as HIV-related stigma, fear of HIV transmission to the uninfected partner and child, fear of unfamiliar medical procedures and lack of information among community members and health care providers about HIV prevention interventions that allow safer conception. Access to information, community experiences with successful safer conception interventions, healthcare provider training, male engagement and community mobilization may help overcome these barriers. Though assisted reproduction strategies generated the most negative reactions from participants, our results suggest that with education and explanation of these services, participants express interest in these strategies and want them to be offered in their community. Many community members noted a need and desire for safer conception education and services in Kisumu. However, community barriers such as fear, stigma and lack of information should be addressed before safer conception interventions can be successfully implemented and delivered. Further research focused on community education, male engagement and healthcare provider training is a crucial next step in delivering safer conception in this region.

Vaccine

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators... more Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a...

Sexually transmitted infections

Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in yo... more Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in young female subjects recruited for a safety and immunogenicity trial of the bivalent HPV-16/18 vaccine in Tanzania. Methods Healthy HIV negative female subjects aged 10–25 years were enrolled and randomised (2:1) to receive HPV-16/18 vaccine or placebo (Al(OH)3 control). At enrolment, if sexually active, genital specimens were collected for HPV DNA, other reproductive tract infections and cervical cytology. Subjects were followed to 12 months when HPV testing was repeated. Results In total 334 participants were enrolled; 221 and 113 in vaccine and control arms, respectively. At enrolment, 74% of 142 sexually active subjects had HPV infection of whom 69% had >1 genotype. Prevalent infections were HPV-45 (16%), HPV-53 (14%), HPV-16 (13%) and HPV-58 (13%). Only age was associated with prevalent HPV infection at enrolment. Among 23 girls who reported age at first sex as 1 year younger than...

Malaria Journal

As malaria transmission declines, continued improvements of prevention and control interventions ... more As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elim...

Perspectives on sexual and reproductive health, 2013

Although intimate partner violence and anal intercourse are common in young adult relationships, ... more Although intimate partner violence and anal intercourse are common in young adult relationships, few studies have examined whether these behaviors are associated with each other. Data from 6,280 women aged 18-28 who took part in Wave 3 of the National Longitudinal Study of Adolescent Health were used to examine the association between physical and sexual intimate partner violence and anal intercourse in 10,462 relationships. Multivariate hierarchical random effects models were used to adjust for the clustered survey design and for the multiple relationships reported per participant. Physical violence occurred in 29% of relationships, sexual violence in 11% and anal intercourse in 14%. The odds that a couple had had anal intercourse were greater among relationships that included physical violence perpetrated by both partners or only by the woman than among nonviolent relationships (odds ratios, 1.7 and 1.9, respectively). The odds of anal intercourse were also elevated among sexually...

The Journal of infectious diseases, 2013

Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of... more Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact. In this phase IIIb, double-blind, randomized, placebo-controlled, multicenter trial (NCT00481767), healthy African girls and young women seronegative for human immunodeficiency virus (HIV) were stratified by age (10-14 or 15-25 years) and randomized (2:1) to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 450) or placebo (n = 226) at 0, 1, and 6 months. The primary objective was to evaluate HPV-16/18 antibody responses at month 7. Seropositivity rates and corresponding geometric mean titers (GMTs) were measured by enzyme-linked immunosorbent assay. In the according-to-protocol analysis at month 7, 100% of initially seronegative participants in the vaccine group were seropositive for both anti-HPV-16 and anti-HPV-18 antibodies (n = 130 and n = 128 for 10-14-year-olds, respectively; n = 190 and n = 21...

PLoS ONE, 2014

Background: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectiona... more Background: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.

Sexually Transmitted Diseases, 2012

Background: Intimate partner violence (IPV) is common among young adult relationships, and is ass... more Background: Intimate partner violence (IPV) is common among young adult relationships, and is associated with significant morbidity, including sexually transmitted infections (STI). This study measured the association between IPV victimization and perpetration and prevalent STIs and STI-risk behaviors among a sample of young women.

Sexually Transmitted Diseases, 2006

The objective of this study was to determine the incidence of HIV-1. The goal of this study was t... more The objective of this study was to determine the incidence of HIV-1. The goal of this study was to inform HIV prevention and vaccine trials by conducting a multisite study in Malawi and Zimbabwe. Women of reproductive age were enrolled in a prospective study. They received 5 intensive HIV counseling and condom promotion sessions over 2 months. Subsequently, HIV-negative women completed quarterly follow-up visits. HIV incidence rates and predictors of HIV acquisition were assessed. A total of 2016 HIV-negative women were enrolled in the condom promotion and counseling phase of the study. Of these, 1679 were tested for HIV during follow up and 113 women seroconverted, resulting in an overall HIV incidence rate of 4.7 per 100 women-years (95% confidence interval = 3.8-5.6). Incidence rates were similar across sites. The major predictors of HIV acquisition were young age, presence of sexually transmitted infections, being unmarried, and higher educational level. The incidence of HIV continues to be high among women in both Malawi and Zimbabwe despite counseling and condom promotion.

Sexually Transmitted Diseases, 2009

: To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbab... more : To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women. : A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs. : Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45-5.55), incident HSV-2 (HR = 5.35, 3.06-9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41-8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50-3.01; and intermediate flora: HR = 2.02, 1.39-2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T. vaginalis, and vaginal yeasts, the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora). : A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora.

PLoS ONE, 2011

Objective: To assess the safety of VivaGelH used vaginally twice daily for 14 days among healthy,... more Objective: To assess the safety of VivaGelH used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18-24 years in the USA and Kenya.

PLoS ONE, 2013

Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently ... more Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for crosssectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers.

The Lancet Infectious Diseases, 2005

Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critic... more Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition.

Journal of Infectious Diseases, 2013

Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Ava... more Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact.

AIDS Research and Human Retroviruses, 2012

The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cro... more The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cross-sectional data. This assay misclassifies some individuals with nonrecent HIV infection as recently infected, leading to overestimation of HIV incidence. We analyzed factors associated with misclassification by the BED-CEIA. We analyzed samples from 383 men who were diagnosed with HIV infection less than 1 year after a negative HIV test (Multicenter AIDS Cohort Study). Samples were collected 2-8 years after HIV seroconversion, which was defined as the midpoint between the last negative and first positive HIV test. Samples were analyzed using the BED-CEIA with a cutoff of OD-n ≤ 0.8 for recent infection. Logistic regression was used to identify factors associated with misclassification. Ninety-one (15.1%) of 603 samples were misclassified. In multivariate models, misclassification was independently associated with highly active antiretroviral treatment (HAART) for >2 years, HIV RNA <400 copies/ml, and CD4 cell count <50 or <200 cells/mm(3); adjusted odds ratios (OR) and 95% confidence intervals (CI) were 4.72 (1.35-16.5), 3.96 (1.53-10.3), 6.85 (2.71-17.4), and 11.5 (3.64-36.0), respectively. Among 220 men with paired samples, misclassification 2-4 years after seroconversion was significantly associated with misclassification 6-8 years after seroconversion [adjusted OR: 25.8 (95% CI: 8.17-81.5), p<0.001] after adjusting for race, CD4 cell count, HIV viral load, and HAART use. Low HIV viral load, low CD4 cell count, and >2 years of HAART were significantly associated with misclassification using the BED-CEIA. Some men were persistently misclassified as recently infected up to 8 years after HIV seroconversion.

AIDS, 2014

To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidit... more To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidity) assay among individuals with long-standing HIV infection. Samples were obtained from the Multicenter AIDS Cohort Study and AIDS Linked to the IntraVenous Experience cohort (1089 samples from 667 individuals, 595 samples collected 2-4 years and 494 samples collected 4-8 years after HIV seroconversion). Paired samples from both time points were available for 422 (63.3%) of the 667 individuals. Samples were considered to be misclassified if the LAg-avidity assay result was 1.5 or less normalized optical density (OD-n) units. Overall, 4.8% (52/1089) of the samples were misclassified, including 1.8% [16/884, 95% confidence interval (CI) 1.09-3.06%] of samples from individuals with viral loads above 400 copies/ml and 1.4% (10/705) of samples from individuals with viral loads above 400 copies/ml and CD4 cell counts above 200 cells/μl (95% CI 0.68-2.60%). Age, race, sex, and mode of HIV acquisition were not associated with misclassification. In an adjusted analysis, viral load below 400 copies/ml [adjusted odds ratio (aOR) 3.72, 95% CI 1.61-8.57], CD4 cell count below 50 cells/μl (aOR 5.41, 95% CI 1.86-15.74), and low LAg-avidity result (≤1.5 OD-n) from the earlier time point (aOR 5.60, 95% CI 1.55-20.25) were significantly associated with misclassification. The manufacturer of the LAg-avidity assay recommends excluding individuals from incidence surveys who are receiving antiretroviral therapy, are elite suppressors, or have AIDS (CD4 cell count <200 cells/μl). The results of this study indicate that those exclusions do not remove all sources of assay misclassification among individuals with long-standing HIV infection.

AIDS, 2004

To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital muc... more To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study. HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days. The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively). N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.

AIDS, 2007

An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection amon... more An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results. To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries. Prospective cohort study. HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15-24 months among 4531 sexually active, HIV-uninfected women aged 18-35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates. HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5-5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6-13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7-7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3-17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

AIDS, 2012

Observational studies of a putative association between hormonal contraception (HC) and HIV acqui... more Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.

Objectives—To determine if healthy, young women in sub-Saharan Africa have a more activated immun... more Objectives—To determine if healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4+ T-cells) than a similar population in the US.

Journal of the International AIDS Society, 2015

Safer conception strategies (SCS) have the potential to decrease HIV transmission among HIV-disco... more Safer conception strategies (SCS) have the potential to decrease HIV transmission among HIV-discordant couples who desire children. Community perceptions of SCS may influence the scale-up and uptake of these services, but little is known about how communities will react to these strategies. Without community support for SCS, their success as an HIV prevention tool may be limited. The objective of this study is to characterize community perceptions of SCS for HIV-discordant couples in Kisumu, Kenya, to inform ongoing and future safer conception intervention studies in low-resource settings. We conducted six focus group discussions and 11 in-depth-interviews in Kisumu, Kenya, among a diverse group (N=59) of community members, including men, women, youth (age 19-25), community health workers and local leaders. An iterative qualitative analysis using a grounded theory approach was employed. All participants emphasized the importance of childbearing in their society and the right to have children, regardless of an individual's HIV status. While most participants believed that HIV-discordant couples should be allowed to have children, they discussed several barriers to the uptake of SCS such as HIV-related stigma, fear of HIV transmission to the uninfected partner and child, fear of unfamiliar medical procedures and lack of information among community members and health care providers about HIV prevention interventions that allow safer conception. Access to information, community experiences with successful safer conception interventions, healthcare provider training, male engagement and community mobilization may help overcome these barriers. Though assisted reproduction strategies generated the most negative reactions from participants, our results suggest that with education and explanation of these services, participants express interest in these strategies and want them to be offered in their community. Many community members noted a need and desire for safer conception education and services in Kisumu. However, community barriers such as fear, stigma and lack of information should be addressed before safer conception interventions can be successfully implemented and delivered. Further research focused on community education, male engagement and healthcare provider training is a crucial next step in delivering safer conception in this region.

Vaccine

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators... more Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a...

Sexually transmitted infections

Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in yo... more Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in young female subjects recruited for a safety and immunogenicity trial of the bivalent HPV-16/18 vaccine in Tanzania. Methods Healthy HIV negative female subjects aged 10–25 years were enrolled and randomised (2:1) to receive HPV-16/18 vaccine or placebo (Al(OH)3 control). At enrolment, if sexually active, genital specimens were collected for HPV DNA, other reproductive tract infections and cervical cytology. Subjects were followed to 12 months when HPV testing was repeated. Results In total 334 participants were enrolled; 221 and 113 in vaccine and control arms, respectively. At enrolment, 74% of 142 sexually active subjects had HPV infection of whom 69% had >1 genotype. Prevalent infections were HPV-45 (16%), HPV-53 (14%), HPV-16 (13%) and HPV-58 (13%). Only age was associated with prevalent HPV infection at enrolment. Among 23 girls who reported age at first sex as 1 year younger than...

Malaria Journal

As malaria transmission declines, continued improvements of prevention and control interventions ... more As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elim...

Perspectives on sexual and reproductive health, 2013

Although intimate partner violence and anal intercourse are common in young adult relationships, ... more Although intimate partner violence and anal intercourse are common in young adult relationships, few studies have examined whether these behaviors are associated with each other. Data from 6,280 women aged 18-28 who took part in Wave 3 of the National Longitudinal Study of Adolescent Health were used to examine the association between physical and sexual intimate partner violence and anal intercourse in 10,462 relationships. Multivariate hierarchical random effects models were used to adjust for the clustered survey design and for the multiple relationships reported per participant. Physical violence occurred in 29% of relationships, sexual violence in 11% and anal intercourse in 14%. The odds that a couple had had anal intercourse were greater among relationships that included physical violence perpetrated by both partners or only by the woman than among nonviolent relationships (odds ratios, 1.7 and 1.9, respectively). The odds of anal intercourse were also elevated among sexually...

The Journal of infectious diseases, 2013

Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of... more Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact. In this phase IIIb, double-blind, randomized, placebo-controlled, multicenter trial (NCT00481767), healthy African girls and young women seronegative for human immunodeficiency virus (HIV) were stratified by age (10-14 or 15-25 years) and randomized (2:1) to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 450) or placebo (n = 226) at 0, 1, and 6 months. The primary objective was to evaluate HPV-16/18 antibody responses at month 7. Seropositivity rates and corresponding geometric mean titers (GMTs) were measured by enzyme-linked immunosorbent assay. In the according-to-protocol analysis at month 7, 100% of initially seronegative participants in the vaccine group were seropositive for both anti-HPV-16 and anti-HPV-18 antibodies (n = 130 and n = 128 for 10-14-year-olds, respectively; n = 190 and n = 21...

PLoS ONE, 2014

Background: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectiona... more Background: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.

Sexually Transmitted Diseases, 2012

Background: Intimate partner violence (IPV) is common among young adult relationships, and is ass... more Background: Intimate partner violence (IPV) is common among young adult relationships, and is associated with significant morbidity, including sexually transmitted infections (STI). This study measured the association between IPV victimization and perpetration and prevalent STIs and STI-risk behaviors among a sample of young women.

Sexually Transmitted Diseases, 2006

The objective of this study was to determine the incidence of HIV-1. The goal of this study was t... more The objective of this study was to determine the incidence of HIV-1. The goal of this study was to inform HIV prevention and vaccine trials by conducting a multisite study in Malawi and Zimbabwe. Women of reproductive age were enrolled in a prospective study. They received 5 intensive HIV counseling and condom promotion sessions over 2 months. Subsequently, HIV-negative women completed quarterly follow-up visits. HIV incidence rates and predictors of HIV acquisition were assessed. A total of 2016 HIV-negative women were enrolled in the condom promotion and counseling phase of the study. Of these, 1679 were tested for HIV during follow up and 113 women seroconverted, resulting in an overall HIV incidence rate of 4.7 per 100 women-years (95% confidence interval = 3.8-5.6). Incidence rates were similar across sites. The major predictors of HIV acquisition were young age, presence of sexually transmitted infections, being unmarried, and higher educational level. The incidence of HIV continues to be high among women in both Malawi and Zimbabwe despite counseling and condom promotion.

Sexually Transmitted Diseases, 2009

: To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbab... more : To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women. : A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs. : Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45-5.55), incident HSV-2 (HR = 5.35, 3.06-9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41-8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50-3.01; and intermediate flora: HR = 2.02, 1.39-2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T. vaginalis, and vaginal yeasts, the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora). : A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora.

PLoS ONE, 2011

Objective: To assess the safety of VivaGelH used vaginally twice daily for 14 days among healthy,... more Objective: To assess the safety of VivaGelH used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18-24 years in the USA and Kenya.

PLoS ONE, 2013

Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently ... more Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for crosssectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers.

The Lancet Infectious Diseases, 2005

Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critic... more Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition.

Journal of Infectious Diseases, 2013

Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Ava... more Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact.

AIDS Research and Human Retroviruses, 2012

The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cro... more The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cross-sectional data. This assay misclassifies some individuals with nonrecent HIV infection as recently infected, leading to overestimation of HIV incidence. We analyzed factors associated with misclassification by the BED-CEIA. We analyzed samples from 383 men who were diagnosed with HIV infection less than 1 year after a negative HIV test (Multicenter AIDS Cohort Study). Samples were collected 2-8 years after HIV seroconversion, which was defined as the midpoint between the last negative and first positive HIV test. Samples were analyzed using the BED-CEIA with a cutoff of OD-n ≤ 0.8 for recent infection. Logistic regression was used to identify factors associated with misclassification. Ninety-one (15.1%) of 603 samples were misclassified. In multivariate models, misclassification was independently associated with highly active antiretroviral treatment (HAART) for >2 years, HIV RNA <400 copies/ml, and CD4 cell count <50 or <200 cells/mm(3); adjusted odds ratios (OR) and 95% confidence intervals (CI) were 4.72 (1.35-16.5), 3.96 (1.53-10.3), 6.85 (2.71-17.4), and 11.5 (3.64-36.0), respectively. Among 220 men with paired samples, misclassification 2-4 years after seroconversion was significantly associated with misclassification 6-8 years after seroconversion [adjusted OR: 25.8 (95% CI: 8.17-81.5), p<0.001] after adjusting for race, CD4 cell count, HIV viral load, and HAART use. Low HIV viral load, low CD4 cell count, and >2 years of HAART were significantly associated with misclassification using the BED-CEIA. Some men were persistently misclassified as recently infected up to 8 years after HIV seroconversion.

AIDS, 2014

To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidit... more To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidity) assay among individuals with long-standing HIV infection. Samples were obtained from the Multicenter AIDS Cohort Study and AIDS Linked to the IntraVenous Experience cohort (1089 samples from 667 individuals, 595 samples collected 2-4 years and 494 samples collected 4-8 years after HIV seroconversion). Paired samples from both time points were available for 422 (63.3%) of the 667 individuals. Samples were considered to be misclassified if the LAg-avidity assay result was 1.5 or less normalized optical density (OD-n) units. Overall, 4.8% (52/1089) of the samples were misclassified, including 1.8% [16/884, 95% confidence interval (CI) 1.09-3.06%] of samples from individuals with viral loads above 400 copies/ml and 1.4% (10/705) of samples from individuals with viral loads above 400 copies/ml and CD4 cell counts above 200 cells/μl (95% CI 0.68-2.60%). Age, race, sex, and mode of HIV acquisition were not associated with misclassification. In an adjusted analysis, viral load below 400 copies/ml [adjusted odds ratio (aOR) 3.72, 95% CI 1.61-8.57], CD4 cell count below 50 cells/μl (aOR 5.41, 95% CI 1.86-15.74), and low LAg-avidity result (≤1.5 OD-n) from the earlier time point (aOR 5.60, 95% CI 1.55-20.25) were significantly associated with misclassification. The manufacturer of the LAg-avidity assay recommends excluding individuals from incidence surveys who are receiving antiretroviral therapy, are elite suppressors, or have AIDS (CD4 cell count <200 cells/μl). The results of this study indicate that those exclusions do not remove all sources of assay misclassification among individuals with long-standing HIV infection.

AIDS, 2004

To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital muc... more To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study. HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days. The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively). N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.

AIDS, 2007

An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection amon... more An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results. To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries. Prospective cohort study. HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15-24 months among 4531 sexually active, HIV-uninfected women aged 18-35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates. HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5-5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6-13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7-7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3-17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

AIDS, 2012

Observational studies of a putative association between hormonal contraception (HC) and HIV acqui... more Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.