Edith Nakku-Joloba

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (19)180.93 Total impact

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    ABSTRACT: Background: Despite the high prevalence of herpes simplex virus type 2 (HSV-2) in sub-Saharan Africa, the natural history of infection among Africans is not well characterized. We evaluated the frequency of genital HSV shedding in HIV-seropositive and HIV-seronegative men and women in Uganda. Methods: Ninety-three HSV-2-seropositive Ugandan adults collected anogenital swab specimens for HSV DNA quantification by polymerase chain reaction 3 times daily for 6 weeks. Results: HSV-2 was detected from 2484 of 11 283 swab specimens collected (22%), with a median quantity of 4.3 log10 HSV copies/mL (range, 2.2-8.9 log10 HSV copies/mL). Genital lesions were reported on 749 of 3875 days (19%), and subclinical HSV shedding was detected from 1480 of 9113 swab specimens (16%) collected on days without lesions. Men had higher rates of total HSV shedding (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.3-2.9]; P < .001); subclinical shedding (RR, 1.7 [95% CI, 1.1-2.7]; P = .01), and genital lesions (RR, 2.1 [95% CI, 1.2-3.4]; P = .005), compared with women. No differences in shedding rates or lesion frequency were observed based on HIV serostatus. Conclusions: HSV-2 shedding frequency and quantity are high among HSV-2-seropositive adults in sub-Saharan Africa, including persons with and those without HIV infection. Shedding rates were particularly high among men, which may contribute to the high prevalence of HSV-2 and early acquisition among African women.
    No preview · Article · Oct 2015 · The Journal of Infectious Diseases
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    ABSTRACT: Prevalence of herpes simplex type 2 virus (HSV-2) is high worldwide. Previous studies in Uganda were rural or in women. We estimated age and sex-specific sero-prevalence of HSV-2 in Kampala, Uganda. Using two-stage random sampling stratified on population density, a survey of persons 15-65 years was conducted. Type-specific serological tests for HSV-2, HSV-1(HerpeSelect2 and 1 ELISA), HIV (Rapid tests and ELISA), syphilis (RPR and TPHA) were done. Additional prevalence analysis included post-stratification weighting on the Uganda 2002 Census gender distribution. Among 1124 persons, HSV-2 prevalence was 58% (95% CI: 55, 60), HSV-1; 98% (95% CI: 97.6, 99.1), HIV; 17.7% (95% CI: 14.8, 19.2) and syphilis; 1.7% (95% CI: 1.4, 1.9). Weighted HSV-2 prevalence was 53.8% (Women; 63.8%, men; 43.2%), similar to unweighted data. Weighted HIV prevalence was 20.7% in women, 8.6% in men. Of 165 HIV infected persons, 85.4% had HSV-2. Risk factors for HSV-2 were being a woman (OR 2.0; 95% CI: 1.42, 2.78), age (OR 3.3; 95% CI: 2.43, 4.53), education (OR 1.70; 95% CI: 1.34, 2.34) and HIV (OR 4.5; 95% CI: 2.70, 7.50). Prevalence of HSV-2 and HIV was high especially in women. Syphilis was rare. Awareness of herpes was low. Interventions in young people are needed.
    No preview · Article · Dec 2014 · African health sciences
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    ABSTRACT: Background: Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2). Objective: To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition. Design: Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245) Setting: Multiple sites in Kenya and Uganda. Participants: Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner. Measurements: HSV-2 seroconversion. Results: A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years. Limitation: Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available. Conclusion: Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP.
    No preview · Article · Jul 2014 · Annals of internal medicine

  • No preview · Article · May 2013 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Background and objectives: Heterosexual HIV-1-serodiscordant couples are increasingly recognized as an important source of new HIV-1 infections in sub-Saharan Africa. A simple risk assessment tool could be useful for identifying couples at highest risk for HIV-1 transmission. Methods: Using data from 3 prospective studies of HIV-1-serodiscordant couples from 7 African countries and standard methods for development of clinical prediction rules, the authors derived and validated a risk scoring tool developed from multivariate modeling and composed of key predictors for HIV-1 risk that could be measured in standard research and clinical settings. Results: The final risk score included age of the HIV-1-uninfected partner, married and/or cohabiting partnership, number of children, unprotected sex, uncircumcised male HIV-1-uninfected partner, and plasma HIV-1 RNA in the HIV-1-infected partner. The maximum risk score was 12, scores ≥5 were associated with an annual HIV-1 incidence of >3%, and couples with a score ≥6 accounted for only 28% of the population but 67% of HIV-1 transmissions. The area under the curve for predictive ability of the score was 0.74 (95% confidence interval: 0.70 to 0.78). Internal and external validation showed similar predictive ability of the risk score, even when plasma viral load was excluded from the risk score. Conclusions: A discrete combination of clinical and behavioral characteristics defines highest risk HIV-1-serodiscordant couples. Discriminating highest risk couples for HIV-1 prevention programs and clinical trials using a validated risk score could improve research efficiency and maximize the impact of prevention strategies for reducing HIV-1 transmission.
    No preview · Article · Nov 2012 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Background: Despite the high prevalence of HSV-2 in sub-Saharan Africa, the natural history of the infection among Africans has not been well characterized. We sought to evaluate the frequency of genital HSV shedding in HIV positive and HIV negative men and women. Methods: We recruited HSV-2 seropositive persons (HSV-2 Focus EIA index value >3.5) who were over 18 years of age and not pregnant. HIV-infected persons were eligible if they were antiretroviral naïve and had detectable plasma HIV RNA. Participants were instructed to collect swabs from the genital area 3 times daily for 6 weeks for HSV and return to clinic weekly. Results: Of 197 participants screened for eligibility, 78 participants were enrolled, including 43 women (15 HIV positive) and 35 men (20 HIV positive). Median age of participants was 33 years (range 18-67); 83% had a history of genital ulcers. Among HIV positive persons, 7 had CD4 count < 250 (median 372, range 52-1264). A total of 97% (530/546) of scheduled visits were completed. Median compliance with the 3 times/day swabs was 100% (range 75-100). Overall, 10,080 swabs were collected from the 78 participants. Of the 4033 swabs currently resulted (remaining are pending), the rate of genital HSV detection was 23%. In swabs with HSV detected, the mean quantity was 10 4.4HSV copies per ml. The rate of HSV shedding was 14% (302/2124) for HIV negative women and 27% (267/1005) for HIV positive women. Among men, the rate of shedding was 62% (230/373) for HIV negative and 21% (114/531) for HIV positive. We observed high variability in the shedding rates: 6% of the HIV negative women did not shed any virus whereas 13% had detectable virus in more than 40% of swabs. Among HIV positive women, all shed at least once and 25% shed virus on more than 40% of swabs. Conclusion: We demonstrated the feasibility of three times daily self-collection of swabs for evaluation of genital shedding of HSV-2 among Ugandan HIV positive and HIV negative men and women. The genital HSV shedding rates are high, especially among men, potentially explaining the rapid acquisition of HSV-2 among young African women.
    No preview · Conference Paper · Oct 2012
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    ABSTRACT: Background: Immunogenetic correlates of resistance to HIV-1 in HIV-1-exposed seronegative (HESN) individuals with consistently high exposure may inform HIV-1 prevention strategies. We developed a novel approach for quantifying HIV-1 exposure to identify individuals remaining HIV-1 uninfected despite persistent high exposure. Methods: We used longitudinal predictors of HIV-1 transmission in HIV-1 serodiscordant couples to score HIV-1 exposure and define HESN clusters with persistently high, low, and decreasing risk trajectories. The model was validated in an independent cohort of serodiscordant couples. We describe a statistical tool that can be applied to other HESN cohorts to identify individuals with high exposure to HIV-1. Results: HIV-1 exposure was best quantified by frequency of unprotected sex with, plasma HIV-1 RNA levels among, and presence of genital ulcer disease among HIV-1-infected partners and by age, pregnancy status, herpes simplex virus 2 serostatus, and male circumcision status among HESN participants. Overall, 14% of HESN individuals persistently had high HIV-1 exposure and exhibited a declining incidence of HIV-1 infection over time. Conclusions: A minority of HESN individuals from HIV-1-discordant couples had persistent high HIV-1 exposure over time. Decreasing incidence of infection in this group suggests these individuals were selected for resistance to HIV-1 and may be most appropriate for identifying biological correlates of natural host resistance to HIV-1 infection.
    Preview · Article · Aug 2012 · The Journal of Infectious Diseases
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    ABSTRACT: Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovir's drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence.
    No preview · Article · Aug 2012 · AIDS and Behavior
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    ABSTRACT: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
    Full-text · Article · Jul 2012 · New England Journal of Medicine
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    ABSTRACT: Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6-24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06-3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8-24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12-3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. US National Institutes of Health and the Bill & Melinda Gates Foundation.
    Full-text · Article · Jan 2012 · The Lancet Infectious Diseases
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    ABSTRACT: Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.
    Full-text · Article · Dec 2011 · PLoS ONE
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    ABSTRACT: Intimate partner violence (IPV) is common worldwide and is an important consideration in couples HIV voluntary counseling and testing (CVCT), especially for HIV-serodiscordant couples (i.e. in which only one member is HIV-infected). Prospective study of 3408 HIV-serodiscordant couples (2299 in which the HIV-infected partner was female) from seven countries from East and Southern Africa. At quarterly visits during up to 2 years of follow-up, participants were asked, separately, about IPV perpetrated against them by their partner during the prior 3 months. Correlates of IPV were determined by generalized estimating equations. The majority of couples were married and living together, with an average duration of partnership of approximately 5 years. More than 39,000 quarterly visits were recorded. IPV was reported in 2.7% of visits by HIV-infected women, 2.2% by HIV-uninfected women, 0.9% by HIV-infected men, and 0.7% by HIV-uninfected men. The majority of IPV reports were verbal or a combination of verbal and physical violence. Those who were HIV-infected were more likely to report IPV [for women adjusted odds ratio (AOR) 1.33, P = 0.043; for men AOR 2.20, P = 0.001], but IPV was not significantly associated with risk of HIV seroconversion in HIV-uninfected participants. IPV incidence decreased during follow-up (P < 0.001). During up to 2 years of prospective follow-up, most persons in stable HIV-serodiscordant partnerships who had undergone CVCT did not report IPV. A modest increased risk of IPV was seen for HIV-infected partners, both female and male.
    No preview · Article · Aug 2011 · AIDS (London, England)
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    ABSTRACT: The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future. We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods. 318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention. A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.
    Full-text · Article · Jul 2011 · PLoS ONE
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    ABSTRACT: High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission. Although plasma and genital HIV-1 RNA concentrations are correlated, no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission. In a prospective study of 2521 African HIV-1 serodiscordant couples, we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk. HIV-1 transmission linkage was established within the partnership by viral sequence analysis. We tested endocervical samples from 1805 women, including 46 who transmitted HIV-1 to their partner, and semen samples from 716 men, including 32 who transmitted HIV-1 to their partner. There was a correlation between genital and plasma HIV-1 RNA concentrations: For endocervical swabs, Spearman's rank correlation coefficient ρ was 0.56, and for semen, ρ was 0.55. Each 1.0 log(10) increase in genital HIV-1 RNA was associated with a 2.20-fold (for endocervical swabs: 95% confidence interval, 1.60 to 3.04) and a 1.79-fold (for semen: 95% confidence interval, 1.30 to 2.47) increased risk of HIV-1 transmission. Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity (hazard ratio, 1.67 for endocervical swabs and 1.68 for semen). Seven female-to-male and four male-to-female HIV-1 transmissions (incidence <1% per year) occurred from persons with undetectable genital HIV-1 RNA, but in all 11 cases, plasma HIV-1 RNA was detected. Thus, higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission, and this effect was independent of plasma HIV-1 concentrations. These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk.
    Full-text · Article · Apr 2011 · Science translational medicine
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    ABSTRACT: Background Hormonal contraceptives are used widely but their eff ects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners.
    No preview · Article · Jan 2011 · The Lancet Infectious Diseases

  • No preview · Conference Paper · Oct 2010

  • No preview · Conference Paper · Oct 2010
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    ABSTRACT: Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We characterized HSV-2 serology assay performance in HIV-positive and HIV-negative Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2 serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was compared with HSV-2 Western blot (WB) according to HIV-1 serostatus. Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and 97.5%/96.2% for Kalon. Focus with Biokit confirmation improved sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%. Kalon had higher specificity than Focus (P < 0.001). Of commercially available HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1 public health activities in Africa.
    Full-text · Article · Sep 2010 · International Journal of STD & AIDS
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    ABSTRACT: Male circumcision for HIV-1 prevention will require high uptake among at-risk populations. 318 HIV-1 serodiscordant couples in Kampala, Uganda [155 (48.7%) with HIV-1 uninfected male partners] were interviewed about male circumcision for HIV-1 prevention. 77.1% of men and 89.6% of women were aware that circumcision reduces men's risk for HIV-1 acquisition. Almost all understood the partial protective efficacy of circumcision for HIV-1 acquisition and lack of reduced HIV-1 transmission from circumcising HIV-1 infected men. Among couples with uncircumcised HIV-1 negative men (n = 92), 53.3% of men and 88.1% of female partners expressed interest in male circumcision. Previous discussion within the couple about circumcision for HIV-1 prevention was significantly associated with interest in the procedure. HIV-1 serodiscordant couples in Uganda demonstrated a high level of understanding of the partial protective effect of male circumcision for HIV-1 prevention, but only half of HIV-1 uninfected uncircumcised men expressed interest in the procedure.
    No preview · Article · Apr 2010 · AIDS and Behavior

Publication Stats

1k Citations
180.93 Total Impact Points

Institutions

  • 2014
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2010-2014
    • Makerere University
      • • Infectious Diseases Institute
      • • School of Public Health
      Kampala, Central Region, Uganda
  • 2012
    • Mulago Hospital
      Kampala, Central Region, Uganda
    • University of Washington Seattle
      • Department of Global Health
      Seattle, Washington, United States