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Introduction: Adolescent girls and young women (AGYW) who may benefit from HIV pre-exposure prophylaxis (PrEP) face high levels of common mental disorders (e.g. depression, anxiety). Common mental disorders can reduce PrEP adherence and increase HIV risk, yet mental health interventions have not been well-integrated into PrEP delivery., Methods: We conducted a four-phase human-centred design process, from December 2020 to April 2022, to understand mental health challenges among AGYW in Johannesburg, South Africa and barriers to integrated mental health and PrEP services. In the "Discover" phase, we conducted in-depth interviews with AGYW and key informants (KIs) in Johannesburg. We conducted a rapid qualitative analysis, informed by the Consolidated Framework for Implementation Research (CFIR), to identify facilitators and barriers of integrated mental health and PrEP services and mapped barriers to potential implementation strategies. In the "Design" and "Build" phases, we conducted stakeholder workshops to iteratively adapt an evidence-based mental health intervention, the Friendship Bench, and refine implementation strategies for South African PrEP delivery settings. In the "Test" phase, we piloted our adapted Friendship Bench package., Results: Interviews with 70 Discover phase participants (48 AGYW, 22 KIs) revealed the importance of integrated mental health and PrEP services for South African AGYW. Interviewees described barriers and implementation strategies for mental health and PrEP services around the CFIR domains: intervention characteristics (e.g. challenges with AGYW "opening up"); outer Johannesburg setting (e.g. community stigma); inner clinic setting (e.g. judgemental healthcare providers); characteristics of counsellors (e.g. training gaps); and the implementation process (e.g. need for demand creation). The Design and Build workshops included 13 AGYW and 15 KIs. Implementation barriers related to the quality and accessibility of public-sector clinic services, lay counsellor training, and community education and demand creation activities were prioritized. This led to 12 key Friendship Bench adaptations and the specification of 10 implementation strategies that were acceptable and feasible in initial pilot testing with three AGYW., Conclusions: Using a human-centred approach, we identified determinants and potential solutions for integrating mental health interventions within PrEP services for South African AGYW. This design process centred stakeholders' perspectives, enabling rapid development of an adapted Friendship Bench intervention implementation package., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Introduction: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up., Methods: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations., Results: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%)., Conclusions: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa., (© 2023. The Author(s).)

In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets., (© 2023. Springer Nature Limited.)

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Introduction: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues., Design: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities., Methods: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16-49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake., Results: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16-24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised., Conclusion: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services., Competing Interests: The authors have declared that no competing interests exist.

Despite remarkable progress in controlling HIV and TB, Uganda is one of the 30 high-burden TB/HIV countries. Approximately 53,000 Ugandans had a new HIV diagnosis in 2019, and approximately 88,000 Ugandans had a TB diagnosis in 2020. Fellows in the Uganda Public Health Fellowship Program (UPHFP) work directly with the Ministry of Health AIDS and TB Control Programs, the U.S. Centers for Disease Control and Prevention, UPHFP supervisors, and implementing partners to investigate and evaluate HIV-related and TB-related issues. These activities have contributed to the Uganda HIV and TB programs. UPHFP fellows complete projects in 7 competency domains, including outbreak investigations, surveillance evaluations, and data quality improvement. Priority HIV/AIDS/TB information gaps/topics are identified in consultation with key stakeholders, and fellows complete projects to guide program improvements and policy decisions. During 2015-2020, UPHFP fellows implemented 127 HIV and TB projects covering key program areas in AIDS and TB control programs, including care and treatment (16 projects), TB/HIV (18), prevention of mother-to-child HIV transmission (24), key and priority populations (9), pre-exposure and post-exposure prophylaxis (7), adolescent girls and young women (6), service delivery (13), and diagnosis of TB including drug-resistant TB and TB in high-risk groups (32). These projects have helped improve retention, quality of care, and treatment outcomes for people living with HIV, HIV and TB coinfected patients, and TB patients. They have also contributed to the decrease in pediatric TB and infant HIV positivity rates and improved service delivery for key populations. UPHFP results were disseminated to relevant stakeholders such as government departments, implementing partners, districts, and the general community and guided decision making. UPHFP has significantly improved HIV and TB control in Uganda. Other countries with similar programs could benefit from this approach and utilize program fellows to support HIV and TB control., (© Ario et al.)

Background: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited., Methods: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men., Results: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time., Conclusions: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence., Methods: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression., Results: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end., Conclusions: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets., Clinical Trial Number: NCT01965470., Competing Interests: There are no competing interests declared by the authors. Lisa Block, Gene Ussery, and James Miller were employed by Northrup Grumman during this study. However, there are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction., Methods: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env)., Results: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction., Conclusions: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective(s): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 cell counts ≤200 cells/μl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes., Design: A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment., Methods: Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 cell counts ≤200 vs. >200 cells/μl)., Results: Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7-18.8%] of study participants had advanced HIV disease (CD4 cell counts ≤200 cells/μl) at time of clinic linkage. Men were significantly more likely to present with CD4 cell counts 200 cells/μl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5-2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4-3.2 >35 vs. <25 years). Patients with CD4 cell counts 200 cells/μl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1)., Conclusion: Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care.

Background: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana., Methods: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470)., Findings: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029)., Interpretation: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas., Funding: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Funding: The National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, the National Cancer Institute, the National Institute for Allergy and Infectious Diseases Division of Intramural Research, Centers for Disease Control and Prevention Uganda, Karolinska Institutet, and the Johns Hopkins University Center for AIDS Research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission., Methods: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees., Results: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples., Conclusions: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Non-citizens often face barriers to HIV care and treatment. Quantifying knowledge of positive HIV status and antiretroviral therapy (ART) coverage among non-citizens in a high HIV-prevalence country like Botswana that is close to achieving UNAIDS "90-90-90" targets may expose important gaps in achieving universal HIV testing and treatment., Methods: The Botswana Combination Prevention Project (BCPP) is a pair-matched cluster-randomized trial evaluating the impact of prevention interventions on HIV incidence in 30 rural or peri-urban communities. Community case finding and HIV testing were conducted in home and mobile venues in 15 intervention communities from October 2013-September 2017. In this secondary analysis, we compared HIV positivity, knowledge of positive HIV-status, and ART status among all citizens and non-citizens assessed at intake in the intervention communities., Results: HIV status was assessed in 57,556 residents in the intervention communities; 4% (n = 2,463) were non-citizens. Five communities accounted for 81% of the total non-citizens assessed. A lower proportion of non-citizens were HIV-positive (15%; n = 369) compared to citizens (21%; n = 11,416) [p = 0.026]; however, a larger proportion of non-citizens did not know their HIV-positive status prior to BCPP testing (75%) as compared to citizens (15%) [p = 0.003]. Among residents with knowledge of their HIV-positive status before BCPP, 79% of the non-citizens (72/91) were on ART compared to 86% (8,267/9,652) of citizens (p = 0.137)., Conclusions: Although non-citizens were less likely to know their HIV-positive status compared to citizens, there were no differences in treatment uptake among non-citizens and citizens who knew their status. Designing interventions for non-citizens that provide HIV testing and treatment services commensurate to that of citizens as well as targeting communities with the largest number of non-citizens may help close a meaningful gap in the HIV care cascade and ensure ethical treatment for all HIV-positive persons., Trial Registration: ClinicalTrials.gov: NCT01965470 (Botswana Combination Prevention Project)., Competing Interests: The authors have declared that no competing interests exist.

Background: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown., Methods: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals., Results: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35)., Conclusions: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: HIV-1 RNA load is the best biological predictor of HIV transmission and treatment response. The rate of virologic suppression among key subpopulations can guide HIV prevention programs., Methods: The Botswana Combination Prevention Project performed a population-based household survey among adults in 30 communities in Botswana. Data collected included knowledge of HIV-positive status, antiretroviral therapy (ART) coverage, and virologic suppression (HIV-1 RNA ≤400 copies per milliliter). Individuals aged 16-29 years were considered young adults., Results: Among 552 young people living with HIV enrolled with RNA load data and ART status available, 51% (n = 279) had undetectable HIV-1 RNA, including 54% of young women and 32% of young men [sex prevalence ratio (PR): 0.53; 95% confidence interval (CI): 0.43 to 0.80; P < 0.001]. Compared with older adults (30-64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.65; 95% CI: 0.59 to 0.70; P < 0.0001), including both men (PR: 0.43; 95% CI: 0.34 to 0.56; P < 0.0001) and women (PR: 0.67; 95% CI: 0.62 to 0.74; P < 0.0001). Among a subset of people living with HIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95% CI: 0.90 to 0.95; P = <0.0001). Analysis of the care continuum revealed that inferior HIV diagnosis and suboptimal linkage to care are the primary reasons for low virologic suppression among young adults., Conclusions: Young adults in Botswana are significantly less likely to have undetectable HIV-1 RNA load compared with older adults. In the era of broad scale-up of ART, interventions able to diagnose young adults living with HIV and link them to effective therapy are urgently needed.

Background: In Kenya, coverage of antiretroviral therapy (ART) among people with HIV infection has increased from 7% in 2006, to 57% in 2016; and, in western Kenya, coverage of voluntary medical male circumcision (VMMC) increased from 45% in 2008, to 72% in 2014. We investigated trends in HIV prevalence and incidence in a high burden area in western Kenya in 2011-16., Methods: In 2011, 2012, and 2016, population-based surveys were done via a health and demographic surveillance system and home-based counselling and testing in Gem, Siaya County, Kenya, including 28 688, 17 021, and 16 772 individuals aged 15-64 years. Data on demographic variables, self-reported HIV status, and risk factors were collected. Rapid HIV testing was offered to survey participants. Participants were tracked between surveys by use of health and demographic surveillance system identification numbers. HIV prevalence was calculated as a proportion, and HIV incidence was expressed as number of new infections per 1000 person-years of follow-up., Findings: HIV prevalence was stable in participants aged 15-64 years: 15% (4300/28 532) in 2011, 12% (2051/16 875) in 2012, and 15% (2312/15 626) in 2016. Crude prevalences in participants aged 15-34 years were 11% (1893/17 197) in 2011, 10% (1015/10 118) in 2012, and 9% (848/9125) in 2016; adjusted for age and sex these prevalences were 11%, 9%, and 8%. 12 606 (41%) of the 30 520 non-HIV-infected individuals enrolled were seen again in at least one more survey round, and were included in the analysis of HIV incidence. HIV incidence was 11·1 (95% CI 9·1-13·1) per 1000 person-years from 2011 to 2012, and 5·7 (4·6-6·9) per 1000 person-years from 2012 to 2016., Interpretation: With increasing coverage of ART and VMMC, HIV incidence declined substantially in Siaya County between 2011 and 2016. VMMC, but not ART, was suggested to have a direct protective effect, presumably because ART tended to be given to individuals with advanced HIV infection. HIV incidence is still high and not close to the elimination target of one per 1000 person-years. The effect of further scale-up of ART and VMMC needs to be monitored., Funding: Data were collected under Cooperative Agreements with the US Centers for Disease Control and Prevention, with funding from the President's Emergency Fund for AIDS Relief., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

UNAIDS 90-90-90 targets and Fast-Track commitments are presented as precursors to ending the AIDS epidemic by 2030, through effecting a 90% reduction in new HIV infections and AIDS-related deaths from 2010 levels (HIV epidemic control). Botswana, a low to middle-income country with the third-highest HIV prevalence, and Australia, a low-prevalence high-income country with an epidemic concentrated among men who have sex with men (MSM), have made significant strides towards achieving the UNAIDS 90-90-90 targets. These two countries provide lessons for different epidemic settings. This paper discusses the lessons that can be drawn from Botswana and Australia with respect to their success in HIV testing, treatment, viral suppression and other HIV prevention strategies for HIV epidemic control. Botswana and Australia are on target to achieving the 90-90-90 targets for HIV epidemic control, made possible by comprehensive HIV testing and treatment programmes in the two countries. As of 2015, 70% of all people assumed to be living with HIV had viral suppression in Botswana and Australia. However, HIV incidence remains above one per cent in the general population in Botswana and in MSM in Australia. The two countries have demonstrated that rapid HIV testing that is accessible and targeted at key and vulnerable populations is required in order to continue identifying new HIV infections. All citizens living with HIV in both countries are eligible for antiretroviral therapy (ART) and viral load monitoring through government-funded programmes. Notwithstanding their success in reducing HIV transmission to date, programmes in both countries must continue to be supported at current levels to maintain epidemic suppression. Scaled HIV testing, linkage to care, universal ART, monitoring patients on treatment over and above strengthened HIV prevention strategies (e.g. male circumcision and pre-exposure prophylaxis) will all continue to require funding. The progress that Botswana and Australia have made towards meeting the 90-90-90 targets is commendable. However, in order to reduce HIV incidence significantly towards 2030, there is a need for sustained HIV testing, linkage to care and high treatment coverage. Botswana and Australia provide useful lessons for developing countries with generalized epidemics and high-income countries with concentrated epidemics., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Design: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials., Methods: We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations., Results: All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation., Conclusions: We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure., Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052., Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm 3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm 3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation., Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure., Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission., Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis., Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant., Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

Background: HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90)., Methods: A population-based sample of individuals was recruited and interviewed in 30 rural and periurban communities from Oct 30, 2013, to Nov 24, 2015, as part of a large, ongoing community-randomised trial designed to assess the effect of a combination prevention package on HIV incidence. A random sample of about 20% of households in each community was selected. Consenting household residents aged 16-64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in the absence of documentation of positive HIV status. Viral load testing was done in all HIV-infected participants, irrespective of treatment status. We used modified Poisson generalised estimating equations to obtain prevalence ratios, corresponding Huber robust SEs, and 95% Wald CIs to examine associations between individual sociodemographic factors and a binary outcome indicating achievement of the three individual and combined overall 90-90-90 targets. The study is registered at ClinicalTrials.gov, number NCT01965470., Findings: 81% of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12 610 participants surveyed, 3596 (29%) were infected with HIV, and 2995 (83·3%, 95% CI 81·4-85·2) of these individuals already knew their HIV status. Among those who knew their HIV status, 2617 (87·4%, 95% CI 85·8-89·0) were receiving ART (95% of those eligible by national guidelines, and 73% of all infected people). Of the 2609 individuals receiving ART with a viral load measurement, 2517 (96·5%, 95% CI 96·0-97·0) had viral load of 400 copies per mL or less. Overall, 70·2% (95% CI 67·5-73·0) of HIV-infected people had virological suppression, close to the UNAIDS target of 73%., Interpretation: UNAIDS 90-90-90 targets are achievable even in resource-constrained settings with high HIV burden., Funding: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009., Methods: Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time., Results: At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections., Conclusion: Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss., (© 2016 John Wiley & Sons Ltd.)

Objective: To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya., Methods: Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression., Results: Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2-4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002., Conclusions: Recent HIV-1 infection was more frequent among 13-19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.

Cost-effective HIV prevention programs should target persons at high risk of HIV acquisition. We conducted an observational HIV incidence cohort study in Kisumu, Kenya, where HIV prevalence is triple that of the national rate. We used referral and venue-sampling approaches to enroll HIV-negative persons for a 12-month observational cohort, August 2010 to September 2011, collected data using computer-assisted interviews, and performed HIV testing quarterly. Among 1292 eligible persons, 648 (50%) were excluded for HIV positivity and other reasons. Of the 644 enrollees, 52% were women who were significantly older than men (P<.01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person-years=1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR=3.14; 95% CI 1.02-7.34) of whom were ≤25 years. Most new infections occurred in young women, an observation consistent with other findings in sub-Saharan Africa that women aged ≤25 years are an important population for HIV intervention trials in Africa., (© The Author(s) 2013.)

We estimated HIV prevalence and identified correlates of HIV infection among 1106 men and women aged 16-34 years residing in Kisumu, Kenya. Demographic, sexual, and other behavioural data were collected using audio computer-assisted self-interview in conjunction with a medical examination, real-time parallel rapid HIV testing, and laboratory testing for pregnancy, gonorrhoea, chlamydia, syphilis, and herpes simplex virus type 2. Multivariate logistic regression was used to identify variables associated with prevalent HIV infection by gender. Overall HIV prevalence was 12.1%. HIV prevalence among women (17.1%) was approximately two-and-one-half times the prevalence among men (6.6%). Odds of HIV infection in men increased with age (aOR associated with one-year increase in age = 1.21, CI = 1.07-1.35) and were greater among those who were uncircumcised (aOR = 4.42, CI = 1.41-13.89) and those who had an herpes simplex virus type 2-positive (aOR = 3.13, CI = 1.12-8.73) test result. Odds of prevalent HIV infection among women also increased with age (aOR associated with one-year increase in age = 1.16, CI = 1.04-1.29). Women who tested herpes simplex virus type 2 positive had more than three times the odds (aOR = 3.85, CI = 1.38-10.46) of prevalent HIV infection compared with those who tested herpes simplex virus type 2 negative. Tailored sexual health interventions and programs may help mitigate HIV age and gender disparities., (© The Author(s) 2015.)

Background: Females in low and middle income countries (LMICs) have difficulty coping with menstrual needs, but few studies have examined the social or health implications of these needs., Methods: Responses from 3418 menstruating females aged 13-29 years were extracted from an HIV and behavioral risks cross-sectional survey conducted in rural western Kenya. We examined sanitary products used, provision of products from sexual partners or from transactional sex, and demographic and sexual exposures., Results: Overall, 75% of females reported using commercial pads and 25% used traditional materials such as cloth or items like paper or tissue, with 10% of girls <15 years old depending on makeshift items. Two-thirds of females with no education relied on traditional items. Having attended secondary school increased the odds of using commercial pads among married (adjusted odds ratios [AOR] 4.8, 95% confidence interval [CI] 3.25-7.12) and single females (AOR 2.17, 95% CI 1.04-4.55). Married females had lower odds of pad use if they reported early (<12 years of age) compared with later (≥18 years) sexual debut (64% vs. 78%, AOR 0.45, 95% CI 0.21-0.97). Two-thirds of pad users received them from sexual partners. Receipt was lower among married females if partners were violent (AOR 0.67, 95% CI 0.53-0.85). Receipt among single females was higher if they had two or more sexual partners in the past year (AOR 2.11, 95% CI 1.04-4.29). Prevalence of engaging in sex for money to buy pads was low (1.3%); however, 10% of 15-year-olds reported this, with girls ≤15 having significantly higher odds compared with females over 15 (AOR 2.84, 95% CI 0.89-9.11). The odds of having transactional sex for pads was higher among females having two or more partners in the past 12 months (AOR 4.86, 95% CI 2.06-11.43)., Conclusions: Menstrual needs of impoverished females in rural LMICs settings likely leads to increased physical and sexual harms. Studies are required to strengthen knowledge and to evaluate interventions to reduce these harms.

Objective: To identify factors associated with repeat pregnancy subsequent to an index pregnancy among women living with HIV (WLWH) in western Kenya who were enrolled in a 24-month phase-II clinical trial of triple-ART prophylaxis for prevention of mother-to-child transmission, and to contextualize social and cultural influences on WLWH's reproductive decision making., Methods: A mixed-methods approach was used to examine repeat pregnancy within a 24 month period after birth. Counselor-administered questionnaires were collected from 500 WLWH. Forty women (22 with a repeat pregnancy; 18 with no repeat pregnancy) were purposively selected for a qualitative interview (QI). Simple and multiple logistic regression analyses were performed for quantitative data. Thematic coding and saliency analysis were undertaken for qualitative data., Results: Eighty-eight (17.6%) women had a repeat pregnancy. Median maternal age was 23 years (range 15-43 years) and median gestational age at enrollment was 34 weeks. In multiple logistic regression analyses, living in the same compound with a husband (adjusted odds ratio (AOR): 2.33; 95% confidence interval (CI): 1.14, 4.75) was associated with increased odds of repeat pregnancy (p ≤ 0.05). Being in the 30-43 age group (AOR: 0.25; 95% CI: 0.07, 0.87), having talked to a partner about family planning (FP) use (AOR: 0.53; 95% CI: 0.29, 0.98), and prior usage of FP (AOR: 0.45; 95% CI: 0.25, 0.82) were associated with a decrease in odds of repeat pregnancy. QI findings centered on concerns about modern contraception methods (side effects and views that they 'ruined the womb') and a desire to have the right number of children. Religious leaders, family, and the broader community were viewed as reinforcing cultural expectations for married women to have children. Repeat pregnancy was commonly attributed to contraception failure or to lack of knowledge about post-delivery fertility., Conclusions: In addition to cultural context, reproductive health programs for WLWH may need to address issues related to living circumstances and the possibility that reproductive-decision making may extend beyond the woman and her partner.

We determined the prevalence of four sexually transmitted infections and the demographic and behavioural correlates associated with having one or more sexually transmitted infections among participants in an HIV incidence cohort study in Kisumu, western Kenya. Participants were enrolled from a convenience sample and underwent aetiologic sexually transmitted infection investigation. Demographic and behavioural information were collected and basic clinical evaluation performed. Multiple regression analysis was done to determine variables associated with having one or more sexually transmitted infections. We screened 846, 18- to 34-year-olds. One-third had at least one sexually transmitted infection with specific prevalence being: syphilis, 1.6%; gonorrhoea, 2.4%; herpes simplex virus type-2, 29.1%; chlamydia, 2.8%; and HIV, 14.8%. Odds of having any sexually transmitted infection were higher among participants who were women, were aged 20-24 or 30-34 years compared to 18-19 years, had secondary or lower education compared to tertiary education, were divorced, widowed or separated compared to singles, reported having unprotected sex compared to those who did not, reported previous sexually transmitted infection treatment, and tested HIV-positive. Multiple strategies are needed to address the overall high prevalence of sexually transmitted infections as well as the gender disparity found in this Kenyan population. Structural interventions may be beneficial in addressing educational and socio-economic barriers, and increasing the uptake of health-promoting practices., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

While global scale-up of prevention of mother-to-child transmission of HIV (PMTCT) services has been expansive, only half of HIV-infected pregnant women receive antiretroviral regimens for PMTCT in sub-Saharan Africa. To evaluate social factors influencing uptake of PMTCT in rural Kenya, we conducted a community-based, cross-sectional survey of mothers residing in the KEMRI/CDC Health and Demographic Surveillance System (HDSS) area. Factors included referrals and acceptability, HIV-related stigma, observed discrimination, and knowledge of violence. Chi-squared tests and multivariate regression analyses were used to detect stigma domains associated with uptake of PMTCT services. Most HIV-positive women (89%) reported blame or judgment of people with HIV, and 46% reported they would feel shame if they were associated with someone with HIV. In multivariate analyses, shame was significantly associated with decreased likelihood of maternal HIV testing (Prevalence Ratio 0.91, 95% Confidence Interval 0.84-0.99), a complete course of maternal antiretrovirals (ARVs) (PR 0.73, 95% CI 0.55-0.97), and infant HIV testing (PR 0.86, 95% CI 0.75-0.99). Community perceptions of why women may be unwilling to take ARVs included stigma, guilt, lack of knowledge, denial, stress, and despair or futility. Interventions that seek to decrease maternal depression and internalization of stigma may facilitate uptake of PMTCT.

Introduction: Facility-based assessments of prevention of mother-to-child HIV transmission (PMTCT) programs may overestimate population coverage. There are few community-based studies that evaluate PMTCT coverage and uptake., Methods: During 2011, a cross-sectional community survey among women who gave birth in the prior year was performed using the KEMRI-CDC Health and Demographic Surveillance System in Western Kenya. A random sample (n = 405) and a sample of women known to be HIV-positive through previous home-based testing (n = 247) were enrolled. Rates and correlates of uptake of antenatal care (ANC), HIV-testing, and antiretrovirals (ARVs) were determined., Results: Among 405 women in the random sample, 379 (94%) reported accessing ANC, most of whom (87%) were HIV tested. Uptake of HIV testing was associated with employment, higher socioeconomic status, and partner HIV testing. Among 247 known HIV-positive women, 173 (70%) self-disclosed their HIV status. Among 216 self-reported HIV-positive women (including 43 from the random sample), 82% took PMTCT ARVs, with 54% completing the full antenatal, peripartum, and postpartum course. Maternal ARV use was associated with more ANC visits and having an HIV tested partner. ARV use during delivery was lowest (62%) and associated with facility delivery. Eighty percent of HIV infected women reported having their infant HIV tested, 11% of whom reported their child was HIV infected, 76% uninfected, 6% declined to say, 7% did not recall; 79% of infected children were reportedly receiving HIV care and treatment., Conclusions: Community-based assessments provide data that complements clinic-based PMTCT evaluations. In this survey, antenatal HIV test uptake was high; most HIV infected women received ARVs, though many women did not self-disclose HIV status to field team. Community-driven strategies that encourage early ANC, partner involvement, and skilled delivery, and provide PMTCT education, may facilitate further reductions in vertical transmission.

Objective(s): HIV stigma is considered to be a major driver of the HIV/AIDS pandemic, yet there is a limited understanding of its occurrence. We describe the geographic patterns of two forms of HIV stigma in a cross-sectional sample of women of childbearing age from western Kenya: internalized stigma (associated with shame) and externalized stigma (associated with blame)., Design: Geographic studies of HIV stigma provide a first step in generating hypotheses regarding potential community-level causes of stigma and may lead to more effective community-level interventions., Methods: Spatial regression using generalized additive models and point pattern analyses using K-functions were used to assess the spatial scale(s) at which each form of HIV stigma clusters, and to assess whether the spatial clustering of each stigma indicator was present after adjustment for individual-level characteristics., Results: There was evidence that externalized stigma (blame) was geographically heterogeneous across the study area, even after controlling for individual-level factors (P=0.01). In contrast, there was less evidence (P=0.70) of spatial trend or clustering of internalized stigma (shame)., Conclusion: Our results may point to differences in the underlying social processes motivating each form of HIV stigma. Externalized stigma may be driven more by cultural beliefs disseminated within communities, whereas internalized stigma may be the result of individual-level characteristics outside the domain of community influence. These data may inform community-level interventions to decrease HIV-related stigma, and thus impact the HIV epidemic.

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

Men who have sex with men (MSM) are a crucial and marginalized at risk population for HIV in Africa but are poorly studied. Like other areas of Africa, homosexuality is illegal in Kenya. We assessed MSM comfort in accessing health services and willingness to participate in HIV prevention research in Kisumu, Kenya-an area of high HIV prevalence. We conducted a two-phase formative study with individual interviews (n = 15) and a structured survey (n = 51). Peer contact or snowball method (n = 43, 84.3%) was the primary recruitment strategy used to locate MSM. Exact logistic regression models were used for survey data analysis. Over 60% (32/51) of survey participants were not very comfortable seeking health services from a public hospital. Almost all MSM (49/51; 96.1%) reported willingness to be contacted to participate in future HIV research studies. Efforts to provide facilities that offer safe and confidential health services and health education for MSM is required. Continued community engagement with the MSM population in Kenya is needed to guide best practices for involving them in HIV prevention research.

Background: Preventing unintended pregnancies among HIV-positive women through family planning (FP) reduces pregnancy-related morbidity and mortality, decreases the number of pediatric HIV infections, and has also proven to be a cost-effective way to prevent mother-to-child HIV transmission. A key element of a comprehensive HIV prevention agenda, aimed at avoiding unintended pregnancies, is recognizing the attitudes towards FP among HIV-positive women and their spouse or partner. In this study, we analyze FP attitudes among HIV-infected pregnant women enrolled in a PMTCT clinical trial in Western Kenya., Methods and Findings: Baseline data were collected on 522 HIV-positive pregnant women using structured questionnaires. Associations between demographic variables and the future intention to use FP were examined using Fisher's exact tests and permutation tests. Most participants (87%) indicated that they intended to use FP. However, only 8% indicated condoms as a preferred FP method, and 59% of current pregnancies were unintended. Factors associated with positive intentions to use FP were: marital status (p = 0.04), having talked to their spouse or partner about FP (p<0.001), perceived spouse or partner approval of FP (p<0.001), previous use of a FP method (p = 0.006), attitude toward the current pregnancy (p = 0.02), disclosure of a sexually transmitted infection (STI) diagnosis (p = 0.03) and ethnic group (p = 0.03)., Conclusion: A significant gap exists between future FP intentions and current FP practices. Support and approval by the spouse or partner are key elements of FP intentions. Counseling services should be offered to both members of a couple to increase FP use, especially given the high number of unplanned pregnancies among HIV-positive women. Condoms should be promoted as part of a dual use method for HIV and STI prevention and for contraception. Integration of individual and couple FP services into routine HIV care, treatment and support services is needed in order to avoid unintended pregnancies and to prevent mother-to-child HIV transmission.

In Kenya, HIV-1 viral load monitoring is commonly performed with the Cobas Amplicor using plasma specimens. Interest is growing in transitioning to real-time PCR (RT-PCR), such as the Cobas Ampliprep/Cobas TaqMan (CAP/CTM), using dried blood spots (DBS). Before implementation, direct evaluation of the two assays using DBS field specimens is required. This study compares the sensitivity, specificity, negative and positive predictive values (NPV and PPV, respectively), concordance, and agreement between HIV-1 viral load measurements using plasma and DBS specimens obtained from 512 HIV-1-infected pregnant females enrolled in the Kisumu Breastfeeding Study and tested with the Cobas Amplicor and CAP/CTM assays. The sensitivity and NPV of viral load detection in DBS specimens were higher with CAP/CTM (sensitivity, 100%; 95% confidence interval [CI], 99.1 to 100.0%; NPV, 100%; 95% CI, 59.0 to 100.0%) than the Cobas Amplicor (sensitivity, 96.6%; 95% CI, 94.3 to 98.1%; NPV, 58.8%; 95% CI, 40.7 to 75.4%). The PPVs were comparable between both assays when using DBS. The specificity of viral load detection in DBS specimens was lower with CAP/CTM (77.8%; 95% CI, 40.0 to 97.2%) than that of the Cobas Amplicor (95.2%; 95% CI, 76.2 to 99.9%). Good concordance and agreement were observed when paired plasma and DBS specimens were tested with both assays. Lower specificity with the CAP/CTM is likely due to proviral HIV-1 DNA amplification and lower detection limits with RT-PCR. However, the CAP/CTM has better sensitivity and higher throughput than the Cobas Amplicor. These findings suggest that DBS may be a suitable alternative to plasma when using RT-PCR, which could increase access to viral load monitoring in resource-limited settings.

Men who have sex with men are an important yet marginalised population for HIV prevention in Africa. We conducted a two-phase study (individual qualitative interviews and a survey) of men who have sex with men, aged 18-34 years of age and living in Kisumu, Kenya. Approximately half (27/51) of survey respondents reported belonging to a support group. The odds of belonging to support groups were greater for older men (aged 24-34 versus 18-23 years [OR = 5.20; 95% CI = 1.27-26.66]). More than two-thirds (68.6%) of survey respondents were categorised as having high knowledge of HIV-risk factors. Most respondents (94.1%) correctly reported lack of condom use during vaginal sex as a risk factor for HIV, but slightly fewer (82.4%) recognised lack of condom use during anal sex as an HIV risk factor. Among the 15 interviewees, the following were included as greatest needs: health information (n = 5), safe lubricants (n = 5), condoms (n = 4), healthcare facility or men-who-have-sex-with-men-friendly health services (n = 3) and advocacy (n = 2). Kenyan men who have sex with men have developed support groups and have unmet needs for information, lubricants and condoms and services. Partnering with support groups offers an opportunity for organisations to reach men who have sex with men with accurate health information, provision of safe sexual lubricants, condoms and other health and social services.

We compared adverse events among breast-feeding neonates born to Kenyan mothers receiving triple-antiretroviral therapy, including either nevirapine or nelfinavir. Nevirapine-exposed infants had an absolute increase in the risk of rash but no significant risk differences for hepatotoxicity or high-risk hyperbilirubinemia compared with nelfinavir-exposed infants. From an infant-safety perspective, nevirapine-based regimens given during pregnancy and breast-feeding are viable options where alternatives to breast milk are not safe, affordable or feasible.

Background: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples., Methods: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death., Results: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01)., Conclusions: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

In 2008, a Canadian generic pharmaceutical firm, Apotex Inc. (Apotex), shipped 7 million doses of antiretroviral drugs to Rwanda for the treatment of HIV/AIDS. While this event may be seen as a positive outcome of international patent changes that facilitate the fulfillment of health as a human right, the fact that there has been only one shipment of medication in response to these changes highlights the difficulties with both the Canadian legislation and with the international decisions that it implements. The shipment was authorized under Canada's Access to Medicines Regime (CAMR), which implements the World Trade Organization (WTO) General Council Decision (the Decision), made in 2003, to permit someone other than the patent holder to manufacture a lower-cost version of a patented drug or medical device for export to developing countries that do not have the capacity to manufacture such products. The Decision requires that the developing country announce its intention to use this mechanism, to specify the expected quantity of drugs to be supplied, and to issue a compulsory license for the drugs. The requirement of notification in particular may render developing countries vulnerable to pressure from pharmaceutical firms. Neither the mechanism created by the Decision nor Canadian legislation implementing it have facilitated the export of generic medicines to developing countries. To date, the Canadian shipment is the only one to have occurred using the WTO mechanism.

We compared results of a malaria rapid diagnostic test (Binax Now Malaria, Binax-M, Inverness Medical Innovations, Inc., Waltham, MA) performed at rural mobile clinics in Uganda by clinicians evaluating febrile adult HIV patients to thick smear evaluated at a central laboratory by trained microscopists. Two hundred forty-six samples were analyzed, including 14 (5.7%) which were thick-smear positive for falciparum malaria. Sensitivity of Binax-M compared with thick smear was 85.7% (95% CI: 57.2-98.2), specificity 97.8% (95% CI: 94.9-99.3), positive and negative predictive values were 70.6% (95% CI: 44.0-89.7) and 99.1% (95% CI: 96.8-99.9), respectively. The rapid diagnostic test accurately ruled malaria "in or out" at the point-of-care, facilitating appropriate clinical management and averting unnecessary anti-malarial therapy.

CD4 stabilization tubes have the ability to ensure internal quality control in the human immunodeficiency virus (HIV) monitoring laboratory by maintaining accurate absolute CD4 T-cell counts for up to 6 days. Here, we assessed this technology for its use in an HIV clinical monitoring laboratory in a resource-poor setting in rural Uganda.

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis. [ABSTRACT FROM AUTHOR]

Background: In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum. Methods and Findings: The Kisumu Breastfeeding Study, 2003–2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning–when tARV-PMTCT discontinued–by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4–40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9–5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing. Conclusions: Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+. [ABSTRACT FROM AUTHOR]

Audio computer-assisted self-interview (ACASI) has been shown to reduce interviewer and social desirability bias related to sensitive questions, which can be especially important for studies of sexual behavior and HIV risk. Baseline demographic and HIV risk data were collected using ACASI for 849 adults aged 18–34 (423 males and 426 females) of unknown or HIV-negative status as part of an HIV-incidence cohort study in Kisumu, Kenya. ACASI questionnaires and possible responses were recorded being read either by a male or female voice in the three most commonly used languages (English, Kiswahili, and Dholuo). Participants were randomly assigned to hear either male or female voice. Dependent variables, including 12 sexual behavior questions, were evaluated using logistic regression. No significant differences in responses to the 12 sensitive questions were found for gender of the recorded voice on ACASI or for the interaction between gender of recorded ACASI voice and respondent gender. [ABSTRACT FROM AUTHOR]

In 2008, a Canadian generic pharmaceutical firm, Apotex Inc. (Apotex), shipped 7 million doses of antiretroviral drugs to Rwanda for the treatment of HIV/AIDS. While this event may be seen as a positive outcome of international patent changes that facilitate the fulfillment of health as a human right, the fact that there has been only one shipment of medication in response to these changes highlights the difficulties with both the Canadian legislation and with the international decisions that it implements. The shipment was authorized under Canada's Access to Medicines Regime (CAMR), which implements the World Trade Organization (WTO) General Council Decision (the Decision), made in 2003, to permit someone other than the patent holder to manufacture a lower-cost version of a patented drug or medical device for export to developing countries that do not have the capacity to manufacture such products. The Decision requires that the developing country announce its intention to use this mechanism, to specify the expected quantity of drugs to be supplied, and to issue a compulsory license for the drugs. The requirement of notification in particular may render developing countries vulnerable to pressure from pharmaceutical firms. Neither the mechanism created by the Decision nor Canadian legislation implementing it have facilitated the export of generic medicines to developing countries. To date, the Canadian shipment is the only one to have occurred using the WTO mechanism. [ABSTRACT FROM AUTHOR]