Ronald Gray | Johns Hopkins Bloomberg School of Public Health (original) (raw)

Papers by Ronald Gray

JAMA, 2016

IMPORTANCE Medical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV preven... more IMPORTANCE Medical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV prevention interventions, but there are limited data on the population-level effect of scale-up of these interventions in sub-Saharan Africa. Such evaluation is important for planning and resource allocation. OBJECTIVE To examine whether increasing community MMC and ART coverage was associated with reduced community HIV incidence in Rakai District, Uganda. DESIGN, SETTING, AND PARTICIPANTS Using person-level data from population-based surveys conducted from 1999 through 2013 in 45 rural Rakai communities, community-level ART and MMC coverage, sociodemographics, sexual behaviors, and HIV prevalence and incidence were estimated in 3 periods: prior to the availability of ART and MMC (1999-2004), during early availability of ART and MMC (2004-2007), and during mature program scale-up (2007-2013). EXPOSURES Community MMC coverage in males and ART coverage in HIV-positive persons of the opposite sex based on self-reported MMC status and ART use. MAIN OUTCOMES AND MEASURES Adjusted incidence rate ratios (IRRs) for sex-specific community HIV incidence estimated using multivariable Poisson regression with generalized estimating equations. RESULTS From 1999 through 2013, 44 688 persons participated in 1 or more surveys (mean age at the first survey, 24.6 years [range, 15-49]; female, 56.5%; mean survey participation rate, 92.6% [95% CI, 92.4%-92.7%]). Median community MMC coverage increased from 19% to 39%, and median community ART coverage rose from 0% to 21% in males and from 0% to 26% in females. Median community HIV incidence declined from 1.25 to 0.84 per 100 person-years in males, and from 1.25 to 0.99 per 100 person-years in females. Among males, each 10% increase in community MMC coverage was associated with an adjusted IRR of 0.87 (95% CI, 0.82-0.93). Comparing communities with MMC coverage more than 40% (mean male community incidence, 1.03 per 100 person-years) with communities with coverage of 10% or less (mean male incidence, 1.69 per 100 person-years), the adjusted IRR was 0.61 (95% CI, 0.43-0.88). For each 10% increase in female self-reported ART coverage, there was no significant reduction in male HIV incidence (adjusted IRR, 0.95 [95% CI, 0.81-1.13]). Comparing communities with female ART coverage more than 20% (mean male incidence, 0.87 per 100 person-years) to communities with female ART coverage of 20% or less (mean male incidence, 1.17 per 100 person-years), the adjusted IRR was 0.77 (95% CI, 0.61-0.98). Neither MMC nor male ART coverage was associated with lower female community HIV incidence. CONCLUSIONS AND RELEVANCE In Rakai, Uganda, increasing community MMC and female ART coverage was associated with lower community HIV incidence in males. If similar associations are found elsewhere, this would support further scale-up of MMC and ART for HIV prevention in sub-Saharan Africa.

Sexually transmitted infections, 2013

Human papillomavirus (HPV) infection causes genital warts, penile cancer and cervical cancer. Afr... more Human papillomavirus (HPV) infection causes genital warts, penile cancer and cervical cancer. Africa has one of the highest rates of penile and cervical cancers, but there are little data on high-risk human papillomavirus (HR-HPV) prevalence in heterosexual men. Knowledge of HR-HPV prevalence, risk factors and genotype distribution among heterosexual men is important to establish risk-reduction prevention strategies. 1578 uncircumcised men aged 15-49 years who enrolled in male circumcision trials in Rakai, Uganda, were evaluated for HR-HPV from swabs of the coronal sulcus/glans using Roche HPV Linear Array. Adjusted prevalence risk ratios (adjPRRs) were estimated using modified Poisson multivariable regression. HPV prevalence (either high risk or low risk) was 90.7% (382/421) among HIV-positive men and 60.9% (596/978) among HIV-negative men (PRR 1.49, 95% CI 1.40 to 1.58). HIV-positive men had a significantly higher risk of infection with three or more HR-HPV genotypes (PRR=5.76, 95...

PLoS ONE, 2012

It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more... more It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more thinly keratinized inner foreskin. However, published data are contradictory and potentially confounded by medical indications for circumcision. We tested the hypothesis that the inner foreskin was more thinly keratinized than the outer foreskin using tissues from 19 healthy, HIV-uninfected men undergoing routine prophylactic circumcision in Rakai, Uganda. Sections from 3 foreskin anatomic sites (inner, outer, and frenar band) were snap-frozen separately. Two independent laboratories each separately stained, imaged, and measured keratin thicknesses in a blinded fashion. There was no significant difference in keratin thickness between the inner (mean = 14.6767.48 mm) and outer (mean = 13.3068.49 mm) foreskin, or between the inner foreskin and the frenar band (mean = 16.91612.42 mm). While the frenar band showed the greatest intra-individual heterogeneity in keratin thickness, there was substantial inter-individual variation seen in all regions. Measurements made by the two laboratories showed high correlation (r = 0.741, 95% CI, 0.533-0.864). We conclude that, despite inter-and intra-individual variability, keratin thickness was similar in the inner and outer foreskin of healthy Ugandan men, and that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV acquisition.

The Journal of Infectious Diseases, 2013

Background. Human immunodeficiency virus (HIV)-infected (HIV+) men are more susceptible to sexual... more Background. Human immunodeficiency virus (HIV)-infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections. Methods. Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction. Results. There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm 2 ; P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm 2 ; P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/µL; P < .001). While frequencies of foreskin CC chemokine receptor type 5 + (CCR5 +) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood. Conclusions. Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men.

Journal of Infectious Diseases, 2011

Male circumcision reduces acquisition of herpes simplex virus type 2 (HSV-2) in men. We assessed ... more Male circumcision reduces acquisition of herpes simplex virus type 2 (HSV-2) in men. We assessed whether male circumcision reduces HSV-2 infection among female partners. HSV-2-negative, human immunodeficiency virus-negative female partners of 368 males who were and 372 males who were not randomized to receive male circumcision were enrolled. The incidence of HSV-2 infection among females over a period of 2 years was 6.09 cases per 100 person-years in the intervention arm and 6.32 cases per 100 person-years in the control arm (incidence rate ratio [IRR], 0.96 [95% confidence interval {CI}, .62-1.49]; P 5 .87). Among female partners of HSV-2-positive males, the incidence of HSV-2 infection was 9.55 cases per 100 person-years in the intervention arm and 11.17 cases per 100 person-years in the control arm (IRR, 0.85 [95% CI, .44-1.67]; P 5 .62). Contrary to findings in males, male circumcision did not affect HSV-2 acquisition among female partners.

AIDS, 2013

We assessed whether women had accurate knowledge of their partners' male circumcision (MC) status... more We assessed whether women had accurate knowledge of their partners' male circumcision (MC) status using survey data (2010-2011) from Rakai, Uganda, and examined characteristics of women who misreported MC status. Among couples in which men were uncircumcised (N=1744), 8.2% women misreported; and among couples where men were confirmed circumcised (N=759), 1.2% women misreported. Younger women were 2.2 times more likely to misreport compared to older women. Misreporting was not associated with other sociodemographics or behavioral characteristics. If women are to act as advocates for MC acceptance, there is a need to educate women, particularly younger women about the nature and recognition of MC.

Current Infectious Disease Reports, 2008

Three randomized trials in Africa have shown that adult male circumcision reduces HIV acquisition... more Three randomized trials in Africa have shown that adult male circumcision reduces HIV acquisition in men by approximately 60%. It is biologically plausible that circumcision reduces HIV risk in men because the inner mucosa of the foreskin is lightly keratinized and has a high density of dendritic cells and other HIV target cells, making it vulnerable to HIV infection. Also, the foreskin is retracted over the shaft during intercourse, exposing the inner mucosa to vaginal secretions; the prepuce is vulnerable to trauma during coitus, providing a portal for HIV entry. In addition, circumcision reduces the rate of reported genital ulceration, which is a cofactor for HIV acquisition. Male circumcision may also reduce some other sexually transmitted infections in men and their female partners. For these reasons, male circumcision should be promoted as a component of HIV prevention strategies.

Research Square (Research Square), Mar 17, 2023

HIV incidence in eastern and southern Africa has historically been concentrated among girls and w... more HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years, but as new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance and longitudinal deep- sequence viral phylogenetics to assess how HIV incidence and the population groups driving transmission have evolved over a 15-year period from 2003 to 2018 in Uganda. HIV viral suppression increased more rapidly in women than men, resulting in 1.5-2 fold higher suppression rates in women with HIV by 2018 across age groups. Incidence declined more slowly in women than men, increasing pre-existing gender imbalance in HIV burden. Age-specific transmission flows shifted; the share of transmission to girls and women aged 15-24 years from older men declined by approximately one third, whereas the contribution of transmission to women aged 25-34 years from men aged 0-6 years older doubled from 2003 to 2018. We estimated closing the gender gap in viral sup- pression could have reduced HIV incidence in women by half in 2018 and ended gender disparities in incidence. This study suggests that male-targeted HIV pro- grams to increase HIV suppression are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.

BMC Public Health, Nov 29, 2022

Background: Non-communicable diseases such as cardiovascular conditions and diabetes are rising i... more Background: Non-communicable diseases such as cardiovascular conditions and diabetes are rising in sub-Saharan Africa. Prevention strategies to mitigate non-communicable diseases include improving diet, physical activity, early diagnosis, and long-term management. Early identification of individuals at risk based on risk-score models-such as the Framingham Risk Score (FRS) for 10-year risk of cardiovascular disease and the Finnish type 2 Diabetes risk score (FINDRISC) for type 2 diabetes which are used in high-income settings-have not been well assessed in sub-Saharan Africa. The purpose of this study was to qualitatively assess local knowledge of components of these risk scores in a rural Ugandan setting. Methods: Semi-structured qualitative in-depth interviews were conducted with a purposively selected sample of 15 participants who had responded to the FRS and FINDRISC questionnaires and procedures embedded in the Rakai Community Cohort Study. Data were summarized and categorized using content analysis, with support of Atlas.ti. Results: Participants described local terms for hypertension ("pulessa") and type 2 diabetes ("sukaali"). Most participants understood physical activity as leisure physical activity, but when probed would also include physical activity linked to routine farm work. Vegetables were typically described as "plants", "leafy greens", and "side dish". Vegetable and fruit consumption was described as varying seasonally, with peak availability in December after the rainy season. Participants perceived themselves to have good knowledge about their family members' history of type 2 diabetes and hypertension. Conclusions: While most items of the FRS and FINDRISC were generally well understood, physical activity needs further clarification. It is important to consider the seasonality of fruits and vegetables, especially in rural resource-poor settings. Current risk scores will need to be locally adapted to estimate the 10-year risk of cardiovascular diseases and type 2 diabetes in this setting.

Tobacco Induced Diseases, Feb 28, 2022

INTRODUCTION Tobacco use is a major public health concern, particularly in low-and middle-income ... more INTRODUCTION Tobacco use is a major public health concern, particularly in low-and middle-income countries where 80% of the world's smokers reside. There is limited population-based data from rural Africa on patterns of tobacco smoking and smoker characteristics. We assessed trends in rates of smoking, characteristics of smokers, and factors associated with smoking using repeat population-based cross-sectional surveys in south-central Uganda. METHODS Data accrued over five survey rounds (2010-2018) of the Rakai Community Cohort Study (RCCS) from consenting individuals aged 15-49 years including sociodemographic and behavioral characteristics and smoking status. Proportions of smokers per survey were compared using χ 2 test for trends, and factors associated with smoking were assessed by multivariable logistic regression. RESULTS The prevalence of tobacco smoking in the general population declined from 7.

AIDS, Mar 1, 2002

for the Rakai Project Team Ã Background: Male circumcision is associated with reduced HIV acquisi... more for the Rakai Project Team Ã Background: Male circumcision is associated with reduced HIV acquisition. Methods: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% con®dence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. Results: The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was signi®cantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33±0.87), but not among non-Muslim men. Prepubertal circumcision signi®cantly reduced HIV acquisition (RR 0.49, CI 0.26±0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P 0.004). In couples with HIV-positive men, HIV transmission was signi®cantly reduced in circumcised men with HIV viral loads less than 50 000 copies/ml (P 0.02). Interpretation: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.

The Lancet, 2001

An alternative and more likely explanation is that the association between CD4 cell count and par... more An alternative and more likely explanation is that the association between CD4 cell count and parasite density is the same for HIV-1-positive and HIV-1-negative people, and that the reported differences in slopes are the result of poor fit of the model for HIV-1positive people. Visual inspection of the open circles and closed circles seems to support the notion that at more than 500 cells/L there is no substantial association between CD4 cell count and parasite density in either group. The increase in parasite density in HIV-1positive individuals seems only to occur at values lower than this range. Thus, immunosuppression would affect parasite density only when CD4 cell counts are lower than 500 cells/L, which is a cutoff point used in the Centers for Disease Control Prevention classification system of HIV disease. 2 This effect could be assessed statistically by multivariate regression of parasite density as a function of HIV-1 infection and CD4 cell count, whereby the latter is categorised into two or three strata defined by strategically selected cutoff values. Alternatively, the association could be approximated by a secondorder or probably a third-order polynomial.

AIDS Research and Human Retroviruses, Jul 1, 2012

The foreskin contains a subset of dendritic cells, macrophages, and CD4 + and CD8 + T cells that ... more The foreskin contains a subset of dendritic cells, macrophages, and CD4 + and CD8 + T cells that may be targets for initial HIV infection in female-to-male sexual transmission of HIV-1. We present analyses comparing HIV-1 sequences isolated from foreskin DNA and serum RNA in 12 heterosexual men enrolled in an adult male circumcision trial performed in Rakai, Uganda. Phylogenetic analysis demonstrated three topologies: (1) little divergence between foreskin and serum, (2) multiple genetic bottlenecks occurring in both foreskin and serum, and (3) complete separation of foreskin and serum populations. The latter tree topology provided evidence that foreskin may serve as a reservoir for distinct HIV-1 strains. Distance and recombination analysis also demonstrated that viral genotypes in the foreskin might segregate independently from the circulating pool of viruses.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2021

Background: Sub-Saharan Africa has the highest HIV incidence and prevalence in the world. In the ... more Background: Sub-Saharan Africa has the highest HIV incidence and prevalence in the world. In the past decade, mobile phone ownership has doubled, affecting social and sexual practices. Using longitudinal follow-up data, this study examined whether mobile phone ownership was associated with sexual behaviors and HIV incidence for youth and adults. Methods: The Rakai Community Cohort Study gathers demographic and sexual health information and conducts HIV testing among an open cohort in southcentral Uganda every 12–18 months. Results: Of the 10,618 participants, 58% owned a mobile phone, 69% lived in rural locations, and 77% were sexually active. Analyses were adjusted for time, location, religion, and socioeconomic status. Phone ownership was associated with increased odds of ever having had sex act for 15- to 19-year-olds [men adjusted odds ratio (AOR): 2.12, 95% confidence interval (CI): 1.78 to 2.52; women AOR: 3.20, 95% CI: 2.45 to 4.17]. Among sexually active participants, owning...

The Lancet HIV, 2019

Background Targeting combination HIV interventions to locations and populations with high HIV bur... more Background Targeting combination HIV interventions to locations and populations with high HIV burden is a global priority, but the impact of these strategies on HIV incidence is unclear. We assessed the impact of combination HIV interventions on HIV incidence in four HIV-hyperendemic communities in Uganda. Methods We did an open population-based cohort study of people aged 15-49 years residing in four fishing communities on Lake Victoria. The communities were surveyed five times to collect self-reported demographic, behavioural, and service-uptake data. Free HIV testing was provided at each interview, with referral to combination HIV intervention services as appropriate. From November, 2011, combination HIV intervention services were rapidly expanded in these geographical areas. We evaluated trends in HIV testing coverage among all participants, circumcision coverage among male participants, antiretroviral therapy (ART) coverage and HIV viral load among HIV-positive participants, and sexual behaviours and HIV incidence among HIV-negative participants. Findings From Nov 4, 2011, to Aug 16, 2017, data were collected from five surveys. Overall, 8942 participants contributed 20 721 person-visits; 4619 (52%) of 8942 participants were male. HIV prevalence was 41% (1598 of 3870) in the 2011-12 baseline survey and declined to 37% (1740 of 4738) at the final survey (p<0•0001). 3222 participants who were HIV-negative at baseline, and who had at least one repeat visit, contributed 9477 person-years of follow-up, and 230 incident HIV infections occurred. From the first survey in 2011-12 to the last survey in 2016-17, HIV testing coverage increased from 68% (2613 of 3870) to 96% (4526 of 4738; p<0•0001); male circumcision coverage increased from 35% (698 of 2011) to 65% (1630 of 2525; p<0•0001); ART coverage increased from 16% (254 of 1598) to 82% (1420 of 1740; p<0•0001); and population HIV viral load suppression in all HIV-positive participants increased from 34% (546 of 1596) to 80% (1383 of 1734; p<0•0001). Risky sexual behaviours did not decrease over this period. HIV incidence decreased from 3•43 per 100 person-years (95% CI 2•45-4•67) in 2011-12 to 1•59 per 100 person-years (95% CI 1•19-2•07) in 2016-17; adjusted incidence rate ratio (IRR) 0•52 (95% CI 0•34-0•79). Declines in HIV incidence were similar among men (adjusted IRR 0•53, 95% CI 0•30-0•93) and women (0•51, 0•27-0•96). The risk of incident HIV infection was lower in circumcised men than in uncircumcised men (0•46, 0•32-0•67). Interpretation Rapid expansion of combination HIV interventions in HIV-hyperendemic fishing communities is feasible and could have a substantial impact on HIV incidence. However, incidence remains higher than HIV epidemic control targets, and additional efforts will be needed to achieve this global health priority.

Global Social Welfare, 2015

Background Early entry into HIV care is low in Sub-Saharan Africa. In Rakai, adolescents and youn... more Background Early entry into HIV care is low in Sub-Saharan Africa. In Rakai, adolescents and young adults 15-24 years were at increased risk of not entering care after knowledge of their positive HIV status. This qualitative study explored barriers to entry into care from HIV-positive clients aged 15-24 years and explored the role of economic strengthening in promoting care utilization. Methods We conducted 18 in-depth interviews among HIVinfected individuals aged 15-24 years, who had not entered care within 6 months of result receipt and referral for free care. Also, key informant interviews were conducted with 12 providers. Interviews were audio-recorded and transcripts subjected to thematic content analysis based on the health belief model. Results Barriers to using HIV care included fear of stigma (7/18−39 %) and HIV disclosure and high transport costs. Programmatic barriers included fear of antiretroviral drug side effects, long waiting, and travel times. Denial of HIV status and absence of AIDS symptoms were also barriers. Eight (44 %) of the participants reported economic barriers to care utilization, and these included lack of money for transport to clinic and anticipated lost work time and money resulting from long waiting clinic hours. Conclusion Economic barriers are highly prevalent as obstacles to utilization of care by young people, suggesting the role of economic strengthening for young persons living with HIV, so as to promote utilization of HIV care services.

AIDS, 2014

Objective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse progn... more Objective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIVinfected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFNg) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56 dim NK cells from HIV-infected individuals produced less IFNg in response to IL-12 and IL-18 than did CD56 dim NK cells from uninfected controls. Infected individuals had lower levels of CD56 dim NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A þ CD57 þ CD56 dim NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFNg production correlated directly with coexpression of CD57 and NKG2A on CD56 dim NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A þ CD57 þ CD56 dim NK cell subset, as well as