Cost and Cost-Effectiveness of a Demand Creation Intervention to Increase Uptake of Voluntary Medical Male Circumcision in Tanzania: Spending More to Spend Less.

BACKGROUND: Although voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition, demand for services is lower among men in most at-risk age groups (ages 20-34 years). A randomized controlled trial was conducted to assess the effectiveness of locally-tailored demand creation activities (including mass media, community mobilization, and targeted service delivery) in increasing uptake of campaign-delivered VMMC among men aged 20-34 years. We conducted an economic evaluation to understand the intervention's cost and cost-effectiveness. SETTING: Tanzania (Njombe and Tabora regions). METHODS: Cost data were collected on surgery, demand creation activities, and monitoring and supervision related to VMMC implementation across clusters in both trial arms, as well as start-up activities for the intervention arms. The Decision Makers' Program Planning Tool was used to estimate the number of HIV infections averted and related cost savings, given the total VMMCs per cluster. Disability-adjusted life years were calculated and used to estimate incremental cost-effectiveness ratios. RESULTS: Client load was higher in the intervention arms than in the control arms: 4394 vs. 2901 in Tabora and 1797 vs. 1025 in Njombe, respectively. Despite additional costs of tailored demand creation, demand increased more than proportionally: mean costs per VMMC in the intervention arms were $62 in Tabora and $130 in Njombe, and in the control arms $70 and $191, respectively. More infections were averted in the intervention arm than in the control arm in Tabora (123 vs. 67, respectively) and in Njombe (164 vs. 102, respectively). The intervention dominated the control because it was both less costly and more effective. Cost savings were observed in both regions stemming from the antiretroviral treatment costs averted as a result of the VMMCs performed. CONCLUSIONS: Spending more to address local preferences as a way to increase uptake of VMMC can be cost-saving.

Low levels of viral suppression among refugees and host nationals accessing antiretroviral therapy in a Kenyan refugee camp.

BACKGROUND: Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011-2013) were compared on outcome measures that included viral suppression and adherence to ART. METHODS: This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load <5000 copies/mL. The two study rounds took place in 2011-2013. RESULTS: Among eligible adults, 86% (73/85) of refugees and 84% (86/102) of Kenyan host nationals participated in the Round One survey; 60% (44/73) and 58% (50/86) of Round One participants were recruited for Round Two follow-up viral load testing. In Round One, refugees were older than host nationals (median age 36 years, interquartile range, IQR 31, 41 vs 32 years, IQR 27, 38); the groups had similar time on ART (median 147 weeks, IQR 38, 64 vs 139 weeks, IQR 39, 225). There was weak evidence for a difference between proportions of refugees and host nationals who were virologically suppressed (<5000 copies/mL) after 25 weeks on ART (58% vs 43%, p = 0.10) and no difference in the proportions suppressed at Round Two (74% vs 70%, p = 0.66). Mean adherence within each group in Round One was similar. Refugee status was not associated with viral suppression in multivariable analysis (adjusted odds ratio: 1.69, 95% CI 0.79, 3.57; p = 0.17). Among those not suppressed at either timepoint, 69% (9/13) exhibited resistance mutations. CONCLUSIONS: Virologic outcomes among refugees and host nationals were similar but unacceptably low. Slight improvements were observed after a remedial intervention. Virologic monitoring was important for identifying an underperforming ART program in a remote facility that serves refugees alongside host nationals. This work highlights the importance of careful laboratory monitoring of vulnerable populations accessing ART in remote settings.

Increasing voluntary medical male circumcision uptake among adult men in Tanzania.

OBJECTIVE: We evaluated a demand-creation intervention to increase voluntary medical male circumcision (VMMC) uptake among men aged 20-34 years in Tanzania, to maximise short-term impact on HIV incidence. METHODS: A cluster randomized controlled trial stratified by region was conducted in 20 outreach sites in Njombe and Tabora regions. The sites were randomized 1 : 1 to receive either a demand-creation intervention package in addition to standard VMMC outreach, or standard VMMC outreach alone. The intervention package included enhanced public address messages, peer promotion by recently circumcised men, facility setup to increase privacy, and engagement of female partners in demand creation. The primary outcome was the proportion of VMMC clients aged 20-34 years. FINDINGS: Overall, 6251 and 3968 VMMC clients were enrolled in intervention and control clusters, respectively. The proportion of clients aged 20-34 years was slightly greater in the intervention than control arm [17.7 vs. 13.0%; prevalence ratio = 1.36; 95% confidence intervals (CI):0.9-2.0]. In Njombe region, the proportion of clients aged 20-34 years was similar between arms but a significant two-fold difference was seen in Tabora region (P value for effect modification = 0.006). The mean number of men aged 20-34 years (mean difference per cluster = 97; 95% CI:40-154), and of all ages (mean difference per cluster = 227, 95% CI:33-420) were greater in the intervention than control arm. CONCLUSION: The intervention was associated with a significant increase in the proportion of clients aged 20-34 years in Tabora but not in Njombe. The intervention may be sensitive to regional factors in VMMC programme scale-up, including saturation.

In vivo confocal microscopy appearance of Fusarium and Aspergillus species in fungal keratitis.

BACKGROUND: Clinical outcomes in fungal keratitis vary between Fusarium and Aspergillus spp, therefore distinguishing between species using morphological features such as filament branching angles, sporulation along filaments (adventitious sporulation) or dichotomous branching may be useful. In this study, we assessed these three features within Heidelberg Retina Tomograph 3 in vivo confocal microscopy (IVCM) images from culture-positive Fusarium and Aspergillus spp keratitis participants. METHODS: Prospective observational cohort study in Aravind Eye Hospital (February 2011-February 2012). Eligibility criteria: age ≥18 years, stromal infiltrate ≥3 mm diameter, Fusarium or Aspergillus spp culture-positive. EXCLUSION CRITERIA: previous/current herpetic keratitis, visual acuity <6/60 in fellow eye, >80% corneal thinning. IVCM was performed and images analysed for branch angle, presence/absence of adventitious sporulation or dichotomous branching by a grader masked to the microbiological diagnosis. RESULTS: 98 participants were included (106 eligible, 8 excluded as no measurable branch angles); 68 were positive for Fusarium spp, 30 for Aspergillus spp. Mean branch angle for Fusarium spp was 59.7° (95% CI 57.7° to 61.8°), and for Aspergillus spp was 63.3° (95% CI 60.8° to 65.8°), p=0.07. No adventitious sporulation was detected in Fusarium spp ulcers. Dichotomous branching was detected in 11 ulcers (7 Aspergillus spp, 4 Fusarium spp). CONCLUSIONS: There was very little difference in the branching angle of Fusarium and Aspergillus spp. Adventitious sporulation was not detected and dichotomous branching was infrequently seen. Although IVCM remains a valuable tool to detect fungal filaments in fungal keratitis, it cannot be used to distinguish Fusarium from Aspergillus spp and culture remains essential to determine fungal species.

Prospective Study of the Diagnostic Accuracy of the In Vivo Laser Scanning Confocal Microscope for Severe Microbial Keratitis.

PURPOSE: To determine the diagnostic accuracy of in vivo confocal microscopy (IVCM) for moderate to severe microbial keratitis (MK). DESIGN: Double-masked prospective cohort study. PARTICIPANTS: Consecutive patients presenting to Aravind Eye Hospital, Madurai, India, between February 2012 and February 2013 with MK (diameter ≥3 mm, excluding descemetocele, perforation, or herpetic keratitis). METHODS: Following examination, the corneal ulcer was scanned by IVCM (HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany). Images were graded for the presence or absence of fungal hyphae or Acanthamoeba cysts by the confocal microscopist who performed the scan (masked to microbial diagnosis) and 4 other experienced confocal graders (masked to clinical features and microbiology). The regrading of the shuffled image set was performed by 3 graders, 3 weeks later. Corneal-scrape samples were collected for microscopy and culture. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, and positive and negative predictive values of IVCM compared with those of a reference standard of positive culture or light microscopy. Sensitivities and specificities for multiple graders were pooled and 95% confidence intervals calculated using a bivariate random-effects regression model. RESULTS: The study enrolled 239 patients with MK. Fungal infection was detected in 176 (74%) and Acanthamoeba in 17 (7%) by microbiological methods. IVCM had an overall pooled (5 graders) sensitivity of 85.7% (95% confidence interval [CI]: 82.2%-88.6%) and pooled specificity of 81.4% (95% CI: 76.0%-85.9%) for fungal filament detection. For Acanthamoeba, the pooled sensitivity was 88.2% (95% CI: 76.2%-94.6%) and pooled specificity was 98.2% (95% CI: 94.9%-99.3%). Intergrader agreement was good: κ was 0.88 for definite fungus; κ was 0.72 for definite Acanthamoeba. Intragrader repeatability was high for both definite fungus (κ: 0.88-0.95) and definite Acanthamoeba classification (κ: 0.63-0.90). IVCM images from 11 patients were considered by all 5 graders to have a specific organism present (10 fungus, 1 Acanthamoeba) but had negative results via culture and light microscopy. CONCLUSIONS: Laser scanning IVCM performed with experienced confocal graders has high sensitivity, specificity, and test reproducibility for detecting fungal filaments and Acanthamoeba cysts in moderate to large corneal ulcers in India. This imaging modality was particularly useful for detecting organisms in deep ulcers in which culture and light microscopy results were negative.

Safety, Acceptability, and Feasibility of Early Infant Male Circumcision Conducted by Nurse-Midwives Using the AccuCirc Device: Results of a Field Study in Zimbabwe.

BACKGROUND: For prevention of HIV, early infant male circumcision (EIMC) needs to be scaled up in countries with high HIV prevalence. Routine EIMC will maintain the HIV prevention gains anticipated from current adult male circumcision initiatives. We present here the results of a field study of EIMC conducted in Zimbabwe. METHODS: The study was observational and based on the World Health Organization (WHO) framework for clinical evaluation of male circumcision devices. We recruited parents of newborn male infants between August 2013 and July 2014 from 2 clinics. Nurse-midwives used the AccuCirc device to circumcise eligible infants. We followed participants for 14 days after EIMC. Outcome measures were EIMC safety, acceptability, and feasibility. RESULTS: We enrolled 500 male infants in the field study (uptake 11%). The infants were circumcised between 6 and 60 days postpartum. The procedure took a median of 17 minutes (interquartile range of 5 to 18 minutes). Mothers' knowledge of male circumcision was extensive. Of the 498 mothers who completed the study questionnaire, 91% knew that male circumcision decreases the risk of HIV acquisition, and 83% correctly stated that this prevention is partial. Asked about their community's perception of EIMC, 40% felt that EIMC will likely be viewed positively in their community; 13% said negatively; and 47% said the perception could be both ways. We observed 7 moderate or severe adverse events (1.4%; 95% confidence interval, 0.4% to 2.4%). All resolved without lasting effects. Nearly all mothers (99%) reported great satisfaction with the outcome, would recommend EIMC to other parents, and would circumcise their next sons. CONCLUSION: This first field study in sub-Saharan Africa of the AccuCirc device for EIMC demonstrated that EIMC conducted by nurse-midwives with this device is safe, feasible, and acceptable to parents.

Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

BACKGROUND: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected adults in low- and middle-income countries (LMICs). METHODS: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case. RESULTS: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%-91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, $43.8-$49.4 million). CONCLUSIONS: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.

Using hepatitis C prevalence to estimate HIV epidemic potential among people who inject drugs in the Middle East and North Africa.

OBJECTIVES: The objective of this study is to understand the association between HIV and hepatitis C virus (HCV) among people who inject drugs (PWIDs) in the Middle East and North Africa (MENA), and to estimate HIV epidemic potential among PWIDs using HCV prevalence. DESIGN/METHODS: Using data from a systematic review of HIV and HCV among PWID in MENA, we conducted two analyses, stratified by HIV epidemic state: a meta-analysis of the risk ratio of HCV to HIV prevalence (RRHCV/HIV) using DerSimonian-Laird random-effects models, and multivariable linear regression predicting log HIV prevalence. The HCV-HIV association from both analyses was used to estimate HIV prevalence at endemic equilibrium. We compared predicted with current HIV prevalence to classify HIV epidemic potential at country-level as low, medium or high, using predefined criteria. RESULTS: The review identified 88 HCV prevalence measures among PWID in MENA, of which 54 had a paired HIV prevalence measure. The pooled RRHCV/HIV were 16, 4 and 3 in low-level, emerging and established HIV epidemics, respectively. There was a significant linear relationship between HCV and HIV at endemic equilibrium (P = 0.002). The predicted endemic HIV prevalence ranged between 8% (Tunisia) and 22% (Pakistan). Of the nine countries with data, five have high and three medium HIV epidemic potential. Only one country, Pakistan, appears to have reached saturation. CONCLUSION: HCV prevalence could be a predictor of future endemic HIV prevalence. In MENA, we predict that there will be further HIV epidemic growth among PWID. The proposed methodology can identify PWID populations that should be prioritized for HIV prevention interventions.

Implementation and Operational Research: A Randomized Noninferiority Trial of AccuCirc Device Versus Mogen Clamp for Early Infant Male Circumcision in Zimbabwe.

BACKGROUND: Early infant male circumcision (EIMC) is a potential key HIV prevention intervention, providing it can be safely and efficiently implemented in sub-Saharan Africa. Here, we present results of a randomized noninferiority trial of EIMC comparing the AccuCirc device with Mogen clamp in Zimbabwe. METHODS: Between January and June 2013, eligible infants were randomized to EIMC through either AccuCirc or Mogen clamp conducted by a doctor, using a 2:1 allocation ratio. Participants were followed for 14 days post-EIMC. Primary outcomes for the trial were EIMC safety and acceptability. RESULTS: One hundred fifty male infants were enrolled in the trial and circumcised between 6 and 54 days postpartum (n = 100 AccuCirc; n = 50 Mogen clamp). Twenty-six infants (17%) were born to HIV-infected mothers. We observed 2 moderate adverse events (AEs) [2%, 95% confidence interval (CI): 0.2 to 7.0] in the AccuCirc arm and none (95% CI: 0.0 to 7.1) in the Mogen clamp arm. The cumulative incident risk of AEs was 2.0% higher in the AccuCirc arm compared with the Mogen Clamp arm (95% CI: -0.7 to 4.7). As the 95% CI excludes the predefined noninferiority margin of 6%, the result provides evidence of noninferiority of AccuCirc compared with the Mogen clamp. Nearly all mothers (99.5%) reported great satisfaction with the outcome. All mothers, regardless of arm said they would recommend EIMC to other parents, and would circumcise their next son. CONCLUSIONS: This first randomized trial of AccuCirc versus Mogen clamp for EIMC demonstrated that EIMC using these devices is safe and acceptable to parents. There was no difference in the rate of AEs by device.

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. RESULTS: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). CONCLUSIONS: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. TRIAL REGISTRATION: PACTR201106000300631, registered on 1st June 2011.

Is forced migration a barrier to treatment success? Similar HIV treatment outcomes among refugees and a surrounding host community in Kuala Lumpur, Malaysia.

In response to an absence of studies among refugees and host communities accessing highly active antiretroviral therapy (HAART) in urban settings, our objective was to compare adherence and virological outcomes among clients attending a public clinic in Kuala Lumpur, Malaysia. A cross-sectional survey was conducted among adult clients (≥18 years). Data sources included a structured questionnaire that measured self-reported adherence, a pharmacy-based measure of HAART prescription refills over the previous 24 months, and HIV viral loads. The primary outcome was unsuppressed viral load (≥40 copies/mL). Among a sample of 153 refugees and 148 host community clients, refugees were younger (median age 35 [interquartile range, IQR 31, 39] vs 40 years [IQR 35, 48], p < 0.001), more likely to be female (36 vs 21 %, p = 0.004), and to have been on HAART for less time (61 [IQR 35, 108] vs 153 weeks [IQR 63, 298]; p < 0.001). Among all clients, similar proportions of refugee and host clients were <95 % adherent to pharmacy refills (26 vs 34 %, p = 0.15). When restricting to clients on treatment for ≥25 weeks, similar proportions from each group were not virologically suppressed (19 % of refugees vs 16 % of host clients, p = 0.54). Refugee status was not independently associated with the outcome (adjusted odds ratio, aOR = 1.28, 95 % CI 0.52, 3.14). Overall, the proportions of refugee and host community clients with unsuppressed viral loads and sub-optimal adherence were similar, supporting the idea that refugees in protracted asylum situations are able to sustain good treatment outcomes and should explicitly be included in the HIV strategic plans of host countries with a view to expanding access in accordance with national guidelines for HAART.

Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review.

BACKGROUND: Although the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well established, the evidence base for its diagnostic accuracy for extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory samples is less clearly defined. METHODS: A systematic literature search of 7 electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health Database, Scopus and Cochrane Database) was conducted to identify studies of the diagnostic accuracy of the Xpert assay when testing non-respiratory samples compared with a culture-based reference standard. Data were extracted and study quality was assessed using the QUADAS-2 tool. Sensitivities and specificities were calculated on a per-sample basis, stratified by sample type and smear microscopy status and summarised using forest plots. Pooled estimates were calculated for groups with sufficient data. RESULTS: Twenty-seven studies with a total of 6,026 non-respiratory samples were included. Among the 23 studies comparing Xpert and culture done on the same samples, sensitivity was very heterogeneous with a median sensitivity of 0.83 (IQR, 0.68-0.94) whereas specificities were typically very high (median, 0.98; IQR, 0.89-1.00). The pooled summary estimates of sensitivity when testing smear-positive and smear-negative samples were 0.95 (95% CI 0.91-1.00) and 0.69 (95% CI 0.60-0.80), respectively. Pooled summary estimates of sensitivity varied substantially between sample types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types, 0.88 (95% CI, 0.76-0.94); pleural fluid, 0.34 (95% CI, 0.24-0.44); gastric aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 - 0.85). Median sensitivities when testing cerebrospinal fluid and non-pleural serous fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively. CONCLUSION: Xpert detects with high specificity the vast majority of EPTB cases with smear-positive non-respiratory samples and approximately two-thirds of those with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB, especially when testing cerebrospinal fluid and tissue samples. In addition, it has a high sensitivity for detecting pulmonary TB when using gastric aspirate samples. These findings support recent WHO guidelines regarding the use of Xpert for TB diagnosis from non-respiratory samples.

Human papillomavirus infection and increased risk of HIV acquisition. A systematic review and meta-analysis.

OBJECTIVES: Human papillomavirus (HPV), one of the commonest sexually transmitted infections, may be a cofactor in HIV acquisition. We systematically reviewed the evidence for an association of HPV infection with HIV acquisition in women, heterosexual men and men who have sex with men (MSM). DESIGN: : Systematic review and meta-analysis. METHODS: Studies meeting inclusion criteria in Pubmed, Embase and conference abstracts up to 29 July 2011 were identified. Random effects meta-analyses were performed to calculate summary hazard ratios (HR). Publication bias and statistical heterogeneity were evaluated and population attributable fractions (PAFs) calculated. RESULTS: Eight articles were included, with previously unpublished data from five authors. Seven studies found an association between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women doubled with prevalent HPV infection with any genotype [HR = 2.06 (95% CI = 1.44-2.94), I = 0%], although adjustment for confounders was often inadequate. The effect was similar for high-risk [HR = 1.99 (95% CI = 1.54-2.56), I = 8.4%] and low-risk [HR = 2.01 (95% CI = 1.27-3.20), I = 0%] HPV genotypes with weak evidence of publication bias (P = 0.06). Two studies in men were identified: both showed an association between HPV infection and HIV acquisition. Unpublished data from one of two studies in women indicated an association between genotypes targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to infection with any HPV genotype ranged between 21 and 37%. CONCLUSION: If further studies validate the association between HPV infection and HIV acquisition, HPV vaccines may reduce HIV incidence in high HPV prevalence populations, in addition to preventing cervical cancer. HIV surveillance studies during implementation of HPV vaccine programmes are warranted.

The effects of micronutrient-fortified complementary/replacement food on intestinal permeability and systemic markers of inflammation among maternally HIV-exposed and unexposed Zambian infants.

The present randomised trial investigated the effects of feeding Zambian infants from 6 to 18 months old either a richly or basal micronutrient-fortified complementary/replacement food on gut integrity and systemic inflammation. Blood samples were obtained from all infants (n 743) at 6 and 18 months for the assessment of serum C-reactive protein (CRP) and α1-acid glycoprotein (AGP). A subsample of 502 infants, selected from the main cohort to include a larger proportion of infants with HIV-positive mothers, was assigned to lactulose/mannitol gut permeability tests. Lactulose:mannitol (L:M) ratio analyses were adjusted for baseline urinary L:M ratio, socio-economic status, mother's education, season of birth and baseline stunting, and stratified by maternal antenatal HIV status, child's sex, concurrent breast-feeding status and anaemia at baseline. There was no significant difference in geometric mean L:M ratio between the richly fortified and basal-fortified porridge arms at 12 months (0·47 (95 % CI 0·41, 0·55) v. 0·41 (95 % CI 0·34, 0·49); P = 0·16 adjusted). At 18 months, the richly fortified porridge group had a significantly higher geometric mean L:M ratio than the basal-fortified group (0·23 (95 % CI 0·19, 0·28) v. 0·15 (95 % CI 0·12, 0·19); P = 0·02 adjusted). This effect was evident for all stratifications, significantly among boys (P = 0·04), among the infants of HIV-negative mothers (P = 0·01), among the infants of HIV-negative mothers not concurrently breast-fed (P = 0·01) and among those who were not anaemic at baseline (P = 0·03). CRP, but not AGP, was positively associated with L:M ratio, but there were no significant effects of the diet on either CRP or AGP. In conclusion, a richly fortified complementary/replacement food did not benefit and may have worsened intestinal permeability.

Male circumcision and human papillomavirus infection in men: a systematic review and meta-analysis.

BACKGROUND: We systematically reviewed the evidence for an association between male circumcision and Human Papillomavirus (HPV) infection and genital warts in men. METHODS: PubMed and Embase were searched to 15 September 2010. The measure of effect was the adjusted odds ratio (OR) or rate ratio (RR) when present and the crude estimate otherwise. Random effects meta-analyses were used to calculate summary measures of effect. RESULTS: We identified 23 papers about the association between circumcision and HPV DNA. Circumcised men were less likely to have prevalent genital HPV infection than uncircumcised men (summary OR, 0.57, 95% confidence interval [CI], 0.45-0.71) with between-study heterogeneity (P-heterogeneity = 0.006; I(2) = 50.5%; 19 studies). Similar summary associations were seen in clinical and methodological subgroups. The effect of circumcision was stronger at the glans/corona (OR, 0.47; 95% CI, 0.37-0.60) and urethra (OR, 0.35; 95% CI, 0.12-1.05) compared with sites more distal to the foreskin. There was weak evidence that circumcision was associated with decreased HPV incidence (summary RR, 0.75, 95% CI, 0.57-0.99; 3 studies) and increased HPV clearance (summary RR, 1.33; 95% CI, 0.89-1.98; 3 studies) but no evidence of an association with prevalent genital warts (OR, 0.93, 95% CI, 0.65-1.33; 15 studies). CONCLUSIONS: Several countries are expanding access to voluntary medical male circumcision to reduce HIV prevalence. This could provide additional benefit in reducing HPV prevalence.

Male circumcision and penile cancer: a systematic review and meta-analysis.

OBJECTIVE: We systematically reviewed the evidence of an association between male circumcision and penile cancer. METHODS: Databases were searched using keywords and text terms for the epidemiology of penile cancer. Random effects meta-analyses were used to calculate summary odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: We identified eight papers which evaluated the association of circumcision with penile cancer, of which seven were case-control studies. There was a strong protective effect of childhood/adolescent circumcision on invasive penile cancer (OR = 0.33; 95% CI 0.13-0.83; 3 studies). In two studies, the protective effect of childhood/adolescent circumcision on invasive cancer no longer persisted when analyses were restricted to boys with no history of phimosis. In contrast, there was some evidence that circumcision in adulthood was associated with an increased risk of invasive penile cancer (summary OR = 2.71; 95% CI 0.93-7.94; 3 studies). There was little evidence for an association of penile intra-epithelial neoplasia and in situ penile cancer with circumcision performed at any age. CONCLUSIONS: Men circumcised in childhood/adolescence are at substantially reduced risk of invasive penile cancer, and this effect could be mediated partly through an effect on phimosis. Expansion of circumcision services in sub-Saharan Africa as an HIV prevention strategy may additionally reduce penile cancer risk.

Decreasing trends of bacteraemia among HIV-infected Ugandan adults: incidence, aetiology, clinical outcomes and effect of antiretroviral therapy in a semi-urban setting (2000-2008).

OBJECTIVE: To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting. METHODS: A cohort of HIV-1-infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6-monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 °C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random-effects Poisson regression for the effect of HAART at the population level. RESULTS: A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person-years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrollment (CD4+ T-cell counts and WHO stage) and time since enrollment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART. CONCLUSIONS: HAART availability in a resource-poor setting substantially reduced the trends of bacteraemia among HIV-infected adults. This may further impact on future morbidity and healthcare costs of HIV-infected people.

Multiple HIV-1 infections with evidence of recombination in heterosexual partnerships in a low risk Rural Clinical Cohort in Uganda.

We report on the frequency of multiple infections, generation of recombinants and consequences on disease progression in 35 HIV-1 infected individuals from 7 monogamous and 6 polygamous partnerships within a Rural Clinical Cohort in Uganda. The env-C2V3, gag-p24 and pol-IN genes were sequenced. Single genome amplified half genome sequences were used to map recombination breakpoints. Three participants were dually infected with subtypes A and D, one case with subtype A and A/D recombinant and the fifth with 2 phylogenetically distinct A/D recombinants. Occurrence of A/D recombination was observed in two multiple infected individuals. Rate of late stage WHO events using Cox regression was 3 times greater amongst multiple infected compared to singly infected individuals (hazard ratio 3.35; 95% CI 1.09, 10.3; p=0.049). We have shown that polygamous relationships involving subtype discordant partnerships was a major contributor of multiple infections with generation of inter subtype recombinants in our cohort.

Impact of the MEMA kwa Vijana adolescent sexual and reproductive health interventions on use of health services by young people in rural Mwanza, Tanzania: results of a cluster randomized trial.

PURPOSE: To assess the impact of an adolescent sexual health intervention on the use of health services by young people in Tanzania. METHODS: Twenty communities, including 39 health facilities, were randomly allocated to the intervention or comparison arm. Health workers from the intervention arm were trained in the provision of youth-friendly health services, as part of a package of interventions. Independent process evaluations were conducted in health facilities, and simulated patients visited clinics using sexual and reproductive health problem scenarios. The impact on health facility attendances were assessed in 1998 (baseline) and 1999-2001. Reported sexually transmitted infection (STI) symptoms and use of health services were evaluated in young people in the trial cohort. RESULTS: The mean monthly attendance for STI symptoms per health facility, per month was .5 for young males and 1.0 for young females at baseline. Attendance by young males was greater in the intervention communities in 1999-2000 after adjustment for baseline differences (p = .005), and this difference increased over time (p-trend = .022). The mean difference in attendance was however relatively modest, at 1.1 per month in 2001 after adjustment for baseline (95% CI: .5, 1.7). There was weaker evidence of an intervention effect on attendance by young women (p = .087). Few condoms were distributed, although a greater number were distributed in intervention facilities (p = .008). Generally, intervention health workers tended to be less judgmental and provided more comprehensive information. CONCLUSIONS: Training staff to provide more youth-friendly health services can increase the utilization of health services for suspected STIs by young people, especially among young men.

Male circumcision, HIV and sexually transmitted infections: a review.

Three randomized controlled trials in sub-Saharan Africa have shown that circumcision reduces the risk of acquiring HIV infection in men by approximately 60%. In this paper, we review the evidence that male circumcision protects against infection with HIV and other sexually transmitted infections (STIs) in men and their female partners. Data from the clinical trials indicate that circumcision may be protective against genital ulcer disease, Herpes simplex type 2, Trichomonas vaginalis and human papillomavirus infection in men. No evidence exists of a protective effect against Chlamydia trachomatis or Neisseria gonorrhea. There is weak evidence that circumcision has a direct protective effect on HIV infection in women, although there is likely to be an indirect benefit, since HIV prevalence is likely to be lower in circumcised male partners. Although there is little evidence from the trials of serious adverse events from the procedure and of behavioural risk compensation among circumcised men, essential operational research is being conducted to evaluate these key issues outside the trial setting as circumcision services are expanded. Following the publication of the clinical trial results in early 2007, the World Health Organization/UNAIDS has advised that promotion of male circumcision should be included as an additional HIV strategy for the prevention of heterosexually acquired HIV infection in men in areas of high HIV prevalence. As circumcision services are expanded in settings where resources are limited, non-physician providers including nurses will play an important role in the provision of services.