JAIDS Journal of Acquired Immune Deficiency Syndromes, 2014
Objective-Studies suggest that the prevalence of HIV is higher among long term marital/ consensua... more Objective-Studies suggest that the prevalence of HIV is higher among long term marital/ consensual relationships than in the unmarried. We assessed the risk of incident HIV infection by marital status in rural Rakai, Uganda. Design-Longitudinal data from the Rakai Community Cohort Study (RCCS) between 1999-2011 Methods-We estimated HIV incidence per 100 person years (py) in sexually active individuals aged 15-49 with a total of 44,179.6 person years (py) who were never married (females 2,929py, males 4,261py), currently married or in long-term consensual relationships ("currently married females 29,823py, males 21,299py) and previously married (females 3,563py, males 1,475). Poisson multivariable regression was used to estimate the unadjusted and adjusted incident rate ratios (IRRs) and 95% confidence intervals (95% CI) of HIV acquisition. Results-HIV incidence among currently married persons was 0.93/100py, which was lower than the never married (1.51/100py) and previously married (2.85/100py). The risk of HIV acquisition was significantly lower in the currently married compared to the never married among women (Adj IRR=0.26, 95% CI: 0.16-0.42), but not men (Adj IRR=0.69, 95% CI: 0.31-1.52). HIV incidence was lower among first marriages (0.73/100py) compared to second or higher order marriages (1.38/100py). Multiple sex partners significantly increased the risk of HIV acquisition in both women (Adj IRR=2.53, 95% CI: 1.6, 3.97) and men (Adj IRR=1.77, 95% CI: 1.20-2.60).
Despite growing recognition of the problem, relatively little is known about the issue of coerciv... more Despite growing recognition of the problem, relatively little is known about the issue of coercive sex in developing countries. This study presents findings from a community-based survey of 4279 reproductive-aged women in current partnerships in the Rakai District of Uganda carried out in 1998-99. One in four women in our study report having experienced coercive sex with their current male partner, with most women reporting its occasional occurrence. In a regression analysis of risk factors for coercive sex, conventional socio-demographic characteristics emerged as largely unpredictive of the risk of coercive sex. Behavioral risk factors-most notably, younger age of women at first intercourse and alcohol consumption before sex by the male partner-were strongly and positively related to the risk of coercive sex. Coercive sex was also strongly related to perceptions of the male partner's HIV risk, with women who perceived their partner to be at highest risk experiencing almost thr...
Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been... more Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but fi ndings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women.
Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and... more Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner's Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P ؍ 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence. IMPORTANCE Bacterial vaginosis (BV) is sexually associated but not considered a sexually transmitted disease. Our findings suggest that the uncircumcised penis is an important niche for BV-associated genital anaerobes. In addition, we found a link between extramarital sexual relationships and BV-associated bacteria in men, which parallels earlier findings of the association between sexual activity and BV in women. This suggests the sexual transmissibility of BV-associated bacteria. Reducing bacterial exchange by barrier methods and managing carriage of BV-associated bacteria in men may decrease BV persistence and recurrence in women.
A prospective observational study of 176 HIV and HSV-2 co-infected men was conducted to assess wh... more A prospective observational study of 176 HIV and HSV-2 co-infected men was conducted to assess whether their sexual partners may be at an increased risk of herpes simplex virus type 2 (HSV-2) from male circumcision (MC) wounds. Preoperative and weekly penile lavages were tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated using Poisson regression. Detectable penile HSV-2 shedding was 9.7%(17/176) prior to MC, compared with one week (12.9%;22/170;PRR=1.33;95%CI=0.74-2.38) and two weeks (14.8%;23/155;PRR=1.50;95%CI=0.86-2.62) after MC. HSV-2 shedding was lower among men with healed MC wounds (adjPRR=0.62;95%CI=0.35-1.08). Men undergoing MC should be counseled on sexual abstinence and condom use.
Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with t... more Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation. Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA. Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels. These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression. NCT00405821.
A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported incre... more A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p…
Little is known about the impact of HIV infection on the disruption of families through separatio... more Little is known about the impact of HIV infection on the disruption of families through separation, divorce, and widowhood. Using life tables and multinomial logistic regression, this research examined the influence of HIV status on the risk of separation or divorce and widowhood among women in Rakai, Uganda. The multivariate results revealed that dissolution is more common among HIV-infected women and that infected women in HIV-discordant couples are especially likely to face separation or divorce than women in other HIV-status couples. These results highlight women's vulnerability to the social impact of HIV infection and the importance of dyadic studies of the disruption of unions.
High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-... more High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3....
Vaginal shedding of CMV DNA was determined among 96 women co-infected with HIV, HSV-2 and CMV sta... more Vaginal shedding of CMV DNA was determined among 96 women co-infected with HIV, HSV-2 and CMV starting anti-retroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV viral load and younger age were significantly associated with increased frequency of CMV shedding (p<0.01), Compared to pre-ART, CMV shedding peaked from month two to four after ART initiation suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.
A recent article in the JLM (Boyle GJ and Hill G, ″Sub-Saharan African Randomised Clinical Trials... more A recent article in the JLM (Boyle GJ and Hill G, ″Sub-Saharan African Randomised Clinical Trials into Male Circumcision and HIV Transmission: Methodological, Ethical and Legal Concerns″ (2011) 19 JLM 316) criticises the large randomised controlled trials (RCTs) that scientists, clinicians and policy-makers worldwide have concluded provide compelling evidence in support of voluntary medical male circumcision (VMMC) as an effective HIV prevention strategy. The present article addresses the claims advanced by Boyle and Hill, demonstrating their reliance on outmoded evidence, outlier studies, and flawed statistical analyses. In the current authors' view, their claims portray misunderstandings of the design,
We examined the association between education and prevalent HIV-1 infection in the Rakai district... more We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-speci® c prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% con® dence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically signi® cant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2± 2.1)) for primary education and 1.5 (95% CI: 1.0± 2.2) for secondary education. Strati® ed multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically signi® cant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a signi® cant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.
The diagnosis of childhood illness by maternal health interview surveys is widely used to estimat... more The diagnosis of childhood illness by maternal health interview surveys is widely used to estimate the prevalence of childhood morbidity in developing countries. To determine the validity of interview-based diagnoses, and to define simple, sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers during structured interviews with physicians&#39; diagnoses for 271 children on the Philippine island of Cebu. The 271 children had 318 physician diagnosed illnesses: 105 acute lower respiratory infections (ALRI), 121 diarrhoeas, 36 measles, 50 upper respiratory infections (URTI), 5 roseola infantums and one milaria rubria. An algorithm for measles (age greater than or equal to 120 days, rash and fever greater than or equal to 3 days and fading of rash) had a sensitivity and specificity of 94%. For ALRI an algorithm of cough, dysponea and fever had a sensitivity of 82%, but specificity was lower in comparison with URTI (58%) than with children who had no respiratory illness (79%). Inclusion of signs of respiratory distress (flaring of nostrils, intercostal retraction) raised the specificity to 83-84%, but reduced sensitivity to 68%. Diagnosis of diarrhoea based on frequent loose or liquid stools had a sensitivity of 95-97% and specificity of 80% in children with or without concomitant non-diarrhoeal illnesses. Addition of questions on numbers of stools (greater than or equal to 6 per day), and no signs of dehydration increased specificity to 95% but reduced the sensitivity to 84-86%. However, specific signs of dehydration were not well reported by the mothers.(ABSTRACT TRUNCATED AT 250 WORDS)
Objectives: To assess the safety and acceptance of the PrePex device for medical male circumcisio... more Objectives: To assess the safety and acceptance of the PrePex device for medical male circumcision (MMC) in rural Uganda.
Factors associated with prevalent and incident HIV infection were compared among sexually experie... more Factors associated with prevalent and incident HIV infection were compared among sexually experienced Ugandans aged 15-24. Most factors were similar. However, in women, older age and current marriage were associated with prevalent, but not incident, infection. It is important to recognize the limitations of prevalence analyses for identifying at-risk youth. ª
Methods We used pre-existing clusters of communities randomised as part of a previous family plan... more Methods We used pre-existing clusters of communities randomised as part of a previous family planning trial in this cohort. Four intervention group clusters from the previous trial were provided standard of care HIV services plus a community-level mobilisation intervention to change attitudes, social norms, and behaviours related to IPV, and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking
To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district... more To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. One-year follow-up (1990-1991) in a population-based rural cohort. Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. Mortality in HIV-infected and uninfected persons. Mortality among HIV-seropositive adults aged &gt; or = 15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CI), 6.0-14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% CI, 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2014
Objective-Studies suggest that the prevalence of HIV is higher among long term marital/ consensua... more Objective-Studies suggest that the prevalence of HIV is higher among long term marital/ consensual relationships than in the unmarried. We assessed the risk of incident HIV infection by marital status in rural Rakai, Uganda. Design-Longitudinal data from the Rakai Community Cohort Study (RCCS) between 1999-2011 Methods-We estimated HIV incidence per 100 person years (py) in sexually active individuals aged 15-49 with a total of 44,179.6 person years (py) who were never married (females 2,929py, males 4,261py), currently married or in long-term consensual relationships ("currently married females 29,823py, males 21,299py) and previously married (females 3,563py, males 1,475). Poisson multivariable regression was used to estimate the unadjusted and adjusted incident rate ratios (IRRs) and 95% confidence intervals (95% CI) of HIV acquisition. Results-HIV incidence among currently married persons was 0.93/100py, which was lower than the never married (1.51/100py) and previously married (2.85/100py). The risk of HIV acquisition was significantly lower in the currently married compared to the never married among women (Adj IRR=0.26, 95% CI: 0.16-0.42), but not men (Adj IRR=0.69, 95% CI: 0.31-1.52). HIV incidence was lower among first marriages (0.73/100py) compared to second or higher order marriages (1.38/100py). Multiple sex partners significantly increased the risk of HIV acquisition in both women (Adj IRR=2.53, 95% CI: 1.6, 3.97) and men (Adj IRR=1.77, 95% CI: 1.20-2.60).
Despite growing recognition of the problem, relatively little is known about the issue of coerciv... more Despite growing recognition of the problem, relatively little is known about the issue of coercive sex in developing countries. This study presents findings from a community-based survey of 4279 reproductive-aged women in current partnerships in the Rakai District of Uganda carried out in 1998-99. One in four women in our study report having experienced coercive sex with their current male partner, with most women reporting its occasional occurrence. In a regression analysis of risk factors for coercive sex, conventional socio-demographic characteristics emerged as largely unpredictive of the risk of coercive sex. Behavioral risk factors-most notably, younger age of women at first intercourse and alcohol consumption before sex by the male partner-were strongly and positively related to the risk of coercive sex. Coercive sex was also strongly related to perceptions of the male partner's HIV risk, with women who perceived their partner to be at highest risk experiencing almost thr...
Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been... more Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but fi ndings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women.
Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and... more Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner's Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P ؍ 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence. IMPORTANCE Bacterial vaginosis (BV) is sexually associated but not considered a sexually transmitted disease. Our findings suggest that the uncircumcised penis is an important niche for BV-associated genital anaerobes. In addition, we found a link between extramarital sexual relationships and BV-associated bacteria in men, which parallels earlier findings of the association between sexual activity and BV in women. This suggests the sexual transmissibility of BV-associated bacteria. Reducing bacterial exchange by barrier methods and managing carriage of BV-associated bacteria in men may decrease BV persistence and recurrence in women.
A prospective observational study of 176 HIV and HSV-2 co-infected men was conducted to assess wh... more A prospective observational study of 176 HIV and HSV-2 co-infected men was conducted to assess whether their sexual partners may be at an increased risk of herpes simplex virus type 2 (HSV-2) from male circumcision (MC) wounds. Preoperative and weekly penile lavages were tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated using Poisson regression. Detectable penile HSV-2 shedding was 9.7%(17/176) prior to MC, compared with one week (12.9%;22/170;PRR=1.33;95%CI=0.74-2.38) and two weeks (14.8%;23/155;PRR=1.50;95%CI=0.86-2.62) after MC. HSV-2 shedding was lower among men with healed MC wounds (adjPRR=0.62;95%CI=0.35-1.08). Men undergoing MC should be counseled on sexual abstinence and condom use.
Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with t... more Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation. Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA. Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels. These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression. NCT00405821.
A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported incre... more A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50,000 copies/ml than among those with an HIV plasma VL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p…
Little is known about the impact of HIV infection on the disruption of families through separatio... more Little is known about the impact of HIV infection on the disruption of families through separation, divorce, and widowhood. Using life tables and multinomial logistic regression, this research examined the influence of HIV status on the risk of separation or divorce and widowhood among women in Rakai, Uganda. The multivariate results revealed that dissolution is more common among HIV-infected women and that infected women in HIV-discordant couples are especially likely to face separation or divorce than women in other HIV-status couples. These results highlight women&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s vulnerability to the social impact of HIV infection and the importance of dyadic studies of the disruption of unions.
High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-... more High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3....
Vaginal shedding of CMV DNA was determined among 96 women co-infected with HIV, HSV-2 and CMV sta... more Vaginal shedding of CMV DNA was determined among 96 women co-infected with HIV, HSV-2 and CMV starting anti-retroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV viral load and younger age were significantly associated with increased frequency of CMV shedding (p<0.01), Compared to pre-ART, CMV shedding peaked from month two to four after ART initiation suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.
A recent article in the JLM (Boyle GJ and Hill G, ″Sub-Saharan African Randomised Clinical Trials... more A recent article in the JLM (Boyle GJ and Hill G, ″Sub-Saharan African Randomised Clinical Trials into Male Circumcision and HIV Transmission: Methodological, Ethical and Legal Concerns″ (2011) 19 JLM 316) criticises the large randomised controlled trials (RCTs) that scientists, clinicians and policy-makers worldwide have concluded provide compelling evidence in support of voluntary medical male circumcision (VMMC) as an effective HIV prevention strategy. The present article addresses the claims advanced by Boyle and Hill, demonstrating their reliance on outmoded evidence, outlier studies, and flawed statistical analyses. In the current authors' view, their claims portray misunderstandings of the design,
We examined the association between education and prevalent HIV-1 infection in the Rakai district... more We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-speci® c prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% con® dence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically signi® cant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2± 2.1)) for primary education and 1.5 (95% CI: 1.0± 2.2) for secondary education. Strati® ed multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically signi® cant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a signi® cant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.
The diagnosis of childhood illness by maternal health interview surveys is widely used to estimat... more The diagnosis of childhood illness by maternal health interview surveys is widely used to estimate the prevalence of childhood morbidity in developing countries. To determine the validity of interview-based diagnoses, and to define simple, sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers during structured interviews with physicians&#39; diagnoses for 271 children on the Philippine island of Cebu. The 271 children had 318 physician diagnosed illnesses: 105 acute lower respiratory infections (ALRI), 121 diarrhoeas, 36 measles, 50 upper respiratory infections (URTI), 5 roseola infantums and one milaria rubria. An algorithm for measles (age greater than or equal to 120 days, rash and fever greater than or equal to 3 days and fading of rash) had a sensitivity and specificity of 94%. For ALRI an algorithm of cough, dysponea and fever had a sensitivity of 82%, but specificity was lower in comparison with URTI (58%) than with children who had no respiratory illness (79%). Inclusion of signs of respiratory distress (flaring of nostrils, intercostal retraction) raised the specificity to 83-84%, but reduced sensitivity to 68%. Diagnosis of diarrhoea based on frequent loose or liquid stools had a sensitivity of 95-97% and specificity of 80% in children with or without concomitant non-diarrhoeal illnesses. Addition of questions on numbers of stools (greater than or equal to 6 per day), and no signs of dehydration increased specificity to 95% but reduced the sensitivity to 84-86%. However, specific signs of dehydration were not well reported by the mothers.(ABSTRACT TRUNCATED AT 250 WORDS)
Objectives: To assess the safety and acceptance of the PrePex device for medical male circumcisio... more Objectives: To assess the safety and acceptance of the PrePex device for medical male circumcision (MMC) in rural Uganda.
Factors associated with prevalent and incident HIV infection were compared among sexually experie... more Factors associated with prevalent and incident HIV infection were compared among sexually experienced Ugandans aged 15-24. Most factors were similar. However, in women, older age and current marriage were associated with prevalent, but not incident, infection. It is important to recognize the limitations of prevalence analyses for identifying at-risk youth. ª
Methods We used pre-existing clusters of communities randomised as part of a previous family plan... more Methods We used pre-existing clusters of communities randomised as part of a previous family planning trial in this cohort. Four intervention group clusters from the previous trial were provided standard of care HIV services plus a community-level mobilisation intervention to change attitudes, social norms, and behaviours related to IPV, and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking
To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district... more To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. One-year follow-up (1990-1991) in a population-based rural cohort. Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. Mortality in HIV-infected and uninfected persons. Mortality among HIV-seropositive adults aged &gt; or = 15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CI), 6.0-14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% CI, 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.
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Papers by Ronald Gray