Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 72 Records) |
Query Trace: Pals S[original query] |
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More frequent HIV viral load testing with point-of-care tests detects elevated viral load earlier in postpartum HIV-positive women in a randomized controlled trial in two clinics in Johannesburg, South Africa
Fairlie L , Sawry S , Pals S , Sherman G , Williamson D , Le Roux J , Ngeno B , Berrie L , Diallo K , Cox MH , Mogashoa M , Chersich M , Modi S . J Acquir Immune Defic Syndr 2023 94 (5) 412-420 BACKGROUND: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure. METHODS: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit. Women were randomized 1:1 to arm 1 or 2. Trained staff performed point-of-care VL testing using the Cepheid's Xpert HIV-1 VL assay. We fitted a generalized linear mixed model with VL suppression (<50 copies/mL (cps/mL) and <1000 cps/mL) at enrollment and 6, 12, and 18 months postpartum as the outcome and indicator variables for time, study site, study arm, and interaction variables. The final model tested for a difference by study arm, pooling across time points. RESULTS: Of 405 women enrolled (204 arm 1 and 201 arm 2), 249 (61%) remained in follow-up through 18 months. There was no difference in VL suppression between arms at 6, 12, or 18 months. VL suppression rate (<50 cps/mL) at 18 months was 64.8% in arm 1 and 63.0% in arm 2 (P = 0.27). On bivariate analysis, there was an association with late antenatal booking and being in arm 2 for nonsuppressed VL, but no significant association with breastfeeding. HIV drug resistance was found in 12 of 23 participants (52.2%). CONCLUSION: We found no significant difference in VL suppression with more frequent VL testing in postpartum women living with HIV receiving first-line efavirenz-based antiretroviral treatment. |
Impact of HIV treat-all and complementary policies on ART linkage in 13 PEPFAR-supported African countries
Russell A , Verani AR , Pals S , Reagon VM , Alexander LN , Galloway ET , Mange MM , Kalimugogo P , Nyika P , Fadil YM , Aoko A , Asiimwe FM , Ikpeazu A , Kayira D , Letebele M , Maida A , Magesa D , Mutandi G , Mwila AC , Onotu D , Nkwoh KT , Wangari E . BMC Health Serv Res 2023 23 (1) 1151 BACKGROUND: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries. These countries adopted and implemented Treat-All policies between 2015 and 2018 and were supported by the U.S. Government's President's Emergency Plan for AIDS Relief (PEPFAR). The focuses of this research were to understand 1) linkage rates to ART initiation before and after the adoption of Treat-All in each country; 2) how Treat-All implementation differed across these countries; and 3) whether complementary policies (including same-day treatment initiation, task-shifting, reduced ART visits, and reduced ART pickups) implemented around the same time may have increased ART linkage. METHODS: HIV testing and treatment data were collected by PEPFAR country programs in 13 African countries from 2015 to 2018. These countries were chosen based on the completeness of policy data and availability of program data during the study period. Program data were used to calculate proxy linkage rates. These rates were compared relative to the Treat All adoption period and the adoption of complementary policies. RESULTS: The 13 countries experienced an average increase in ART linkage of 29.3% over the entire study period. In examining individual countries, all but two showed increases in linkage to treatment immediately after Treat All adoption. Across all countries, those that had adopted four or more complementary policies showed an average increased linkage of 39.8% compared to 13.9% in countries with fewer than four complementary policies. CONCLUSIONS: Eleven of 13 country programs examined in this study demonstrated an increase in ART linkage after Treat-All policy adoption. Increases in linkage were associated with complementary policies. When exploring new public health policies, policymakers may consider which complementary policies might also help achieve the desired outcome of the public health policy. |
Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa
Fernandez D , Ali H , Pals S , Alemnji G , Vasireddy V , Siberry GK , Oboho I , Godfrey C . BMC Public Health 2023 23 (1) 1941 BACKGROUND: In sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We included VLS and reported death data for persons aged 15 + years on ART from October-December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS. RESULTS: Mean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15-49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15-49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15-49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001). CONCLUSIONS: The mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended. |
Retrospective longitudinal analysis of low-level viremia among HIV-1 infected adults on antiretroviral therapy in Kenya
Aoko A , Pals S , Ngugi T , Katiku E , Joseph R , Basiye F , Kimanga D , Kimani M , Masamaro K , Ngugi E , Musingila P , Nganga L , Ondondo R , Makory V , Ayugi R , Momanyi L , Mambo B , Bowen N , Okutoyi S , Chun HM . EClinicalMedicine 2023 63 102166 BACKGROUND: HIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. METHODS: We calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL) <1000 copies/mL used to predict the next VL). FINDINGS: Of 793,902 patients with at least one VL, 18.5% had LLV (51-199 cp/mL 11.1%; 200-399 cp/mL 4.0%; and 400-999 cp/mL 3.4%) and 9.2% had virologic non-suppression at initial result. Among all VLs performed, 26.4% were LLV. Among patients with initial LLV, 13.3% and 2.4% progressed to virologic non-suppression and virologic failure, respectively. Compared to virologic suppression (≤50 copies/mL), LLV was associated with increased risk of virologic non-suppression (adjusted relative risk [aRR] 2.43) and virologic failure (aRR 3.86). Risk of virologic failure increased with LLV range (aRR 2.17 with 51-199 copies/mL, aRR 3.98 with 200-399 copies/mL and aRR 7.99 with 400-999 copies/mL). Compared to patients who never received dolutegravir (DTG), patients who initiated DTG had lower risk of virologic non-suppression (aRR 0.60) and virologic failure (aRR 0.51); similarly, patients who transitioned to DTG had lower risk of virologic non-suppression (aRR 0.58) and virologic failure (aRR 0.35) for the same LLV range. INTERPRETATION: Approximately a quarter of patients experienced LLV and had increased risk of virologic non-suppression and failure. Lowering the threshold to define virologic suppression from <1000 to <50 copies/mL to allow for earlier interventions along with universal uptake of DTG may improve individual and program outcomes and progress towards achieving HIV epidemic control. FUNDING: No specific funding was received for the analysis. HIV program support was provided by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC). |
HIV viral load scale-up among children and adolescents: Trends in viral load suppression, sample type and processing in 7 PEPFAR countries, 2015-2018
Hrapcak S , Pals S , Itoh M , Peters N , Carpenter D , Hackett S , Prao AK , Adje-Toure C , Eboi E , Mutisya I , Nyabiage Omoto L , Ondondo RO , Bowen N , Nyanya W , Kayira D , Kaba MD , Mwenda R , Deus MI , Almeida J , Cuco RMM , Boylan A , Beard S , Ashikoto S , van Rooyen G , Kindra G , Diallo K , Carmona S , Nazziwa E , Mwangi C , Ntale J , Ssewanyana I , Nabadda SN , Nabukenya M , Ellenberger D , Rivadeneira E . Pediatr Infect Dis J 2023 42 (4) e102-e104 HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable. |
Evaluation of community-based, mobile HIV-care, peer-delivered linkage case management in Manzini Region, Eswatini
Suraratdecha C , MacKellar D , Hlophe T , Dlamini M , Ujamaa D , Pals S , Dube L , Williams D , Byrd J , Mndzebele P , Behel S , Pathmanathan I , Mazibuko S , Tilahun E , Ryan C . Int J Environ Res Public Health 2022 20 (1) The success of antiretroviral therapy (ART) requires continuous engagement in care and optimal levels of adherence to achieve sustained HIV viral suppression. We evaluated HIV-care cascade costs and outcomes of a community-based, mobile HIV-care, peer-delivered linkage case-management program (CommLink) implemented in Manzini region, Eswatini. Abstraction teams visited referral facilities during July 2019-April 2020 to locate, match, and abstract the clinical data of CommLink clients diagnosed between March 2016 and March 2018. An ingredients-based costing approach was used to assess economic costs associated with CommLink. The estimated total CommLink costs were $2 million. Personnel costs were the dominant component, followed by travel, commodities and supplies, and training. Costs per client tested positive were $499. Costs per client initiated on ART within 7, 30, and 90 days of diagnosis were $2114, $1634, and $1480, respectively. Costs per client initiated and retained on ART 6, 12, and 18 months after diagnosis were $2343, $2378, and $2462, respectively. CommLink outcomes and costs can help inform community-based HIV testing, linkage, and retention programs in other settings to strengthen effectiveness and improve efficiency. |
An evaluation of an enhanced model of integrating family planning into HIV treatment services in Zambia, April 2018 - June 2019
Medley A , Tsiouris F , Pals S , Senyana B , Hanene S , Kayeye S , Casquete RR , Lasry A , Braaten M , Aholou T , Kasonde P , Chisenga T , Mweebo K , Harris TG . J Acquir Immune Defic Syndr 2022 92 (2) 134-143 BACKGROUND: We designed and implemented an enhanced model of integrating family planning (FP) into existing HIV treatment services at six health facilities in Lusaka, Zambia. METHODS: The enhanced model included: improving FP documentation within HIV monitoring systems; training HIV providers in FP services; offering contraceptives within the HIV clinic; and facilitated referral to community-based distributors. Independent samples of women living with HIV (WLHIV) aged ≥16 years were interviewed pre- and post-intervention and their clinical data abstracted from medical charts. Logistic regression models were used to assess differences in key outcomes between the two time periods. RESULTS: A total of 629 WLHIV were interviewed pre-intervention and 684 post-intervention. Current FP use increased from 35% to 49% comparing the pre- and post-intervention periods (P=0.0025). Increased use was seen for injectables (15% vs. 25%, P<0.0001) and implants (5% vs. 8%, P>0.05) but not for pills (10% vs. 8%, P<0.05) or intra-uterine devices (1% vs. 1%, P >0.05). Dual method use (contraceptive + barrier method) increased from 8% to 18% (P=0.0003) while unmet need for FP decreased from 59% to 46% (P=0.0003). Receipt of safer conception counseling increased from 27% to 39% (P<0.0001). The estimated total intervention cost was $83,293 (2018 USD). CONCLUSIONS: Our model of FP/HIV integration significantly increased the number of WLHIV reporting current FP and dual method use, a met need for FP, and safer conception counseling. These results support continued efforts to integrate FP and HIV services to improve women's access to sexual and reproductive health services. |
Survival and epidemiology of amyotrophic lateral sclerosis (ALS) cases in the Chicago and Detroit metropolitan cohort: incident cases 2009-2011 and survival through 2018
Punjani R , Larson TC , Wagner L , Davis B , Horton DK , Kaye W . Amyotroph Lateral Scler Frontotemporal Degener 2022 24 1-9 Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder. The National ALS Registry launched surveillance projects to understand the distribution of ALS in targeted geographic cohorts. Objective: To describe the demographics, incidence, and survival of persons with ALS (PALS) identified in the Chicago and Detroit area population-based cohort. Methods: Neurologists in the catchment area provided case reports for eligible ALS cases diagnosed and/or cared for from 1 January 2009 through 31 December 2011. Crude incidence rates were calculated for 2009-2011 and stratified by race and ethnicity. Using data from the National Death Index through 2018, we modeled the effect of patient covariates on mortality using the Cox proportional hazard regression. Results: Of the 574 cases, 372 (64.8%) were diagnosed from 2009 to 2011. The combined crude incidence rates for 2009, 2010, and 2011 were 1.44, 1.53, and 1.73 cases per 100,000 person-years, respectively. Of the 486 subjects with complete survival data, 81% were deceased at the end of follow-up. Median survival time was 2.2 years, with 30% and 9% of subjects surviving past 5 and 10 years after diagnosis, respectively. Additionally, female PALS and PALS with longer time between symptom onset and diagnosis experienced longer survival. Nonwhites also experienced longer survival than Whites, except for those cases diagnosed in the younger age categories. Conclusion: Understanding the survival of ALS patients can aid in understanding variable prognostic factors, which can potentially extend survival and improve disease management. |
Staff involvement and family and community engagement
Webster CA , Hoke A , Cornett K , Goh TL , Pulling Kuhn A . J Phys Educ Recreat Dance 2022 93 (5) 27-34 The staff involvement (SI) and family and community engagement (FCE) components of the CSPAP framework constitute the support system for program implementation and sustainability. These components embody the essence of the framework because they focus on the coordination and synergy needed for a successful program, and such attributes are the hallmark of multicomponent approaches to school-based health promotion. But what does it take to galvanize school staff, families, and communities in a collective effort to bolster quality physical education and promote and increase the physical activity (PA) of children and adolescents? In this article, the authors summarize research on SI and FCE, particularly over the past decade. While research on these CSPAP components is still in its emergent stages, we identify key findings to date and suggest strategies for translating research to practice. It is our hope that this article will provide school PA leaders (PALs) and physical education teacher educators with actionable ideas to more fully leverage the CSPAP support system. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. |
Antiretroviral therapy initiation and retention among clients who received peer-delivered linkage case management and standard linkage services, Eswatini, 2016-2020: retrospective comparative cohort study
MacKellar D , Hlophe T , Ujamaa D , Pals S , Dlamini M , Dube L , Suraratdecha C , Williams D , Byrd J , Tobias J , Mndzebele P , Behel S , Pathmanathan I , Mazibuko S , Tilahun E , Ryan C . Arch Public Health 2022 80 (1) 74 BACKGROUND: Persons living with HIV infection (PLHIV) who are diagnosed in community settings in sub-Saharan Africa are particularly vulnerable to barriers to care that prevent or delay many from obtaining antiretroviral therapy (ART). METHODS: We conducted a retrospective cohort study to assess if a package of peer-delivered linkage case management and treatment navigation services (CommLink) was more effective than peer-delivered counseling, referral, and telephone follow-up (standard linkage services, SLS) in initiating and retaining PLHIV on ART after diagnosis in community settings in Eswatini. HIV-test records of 773 CommLink and 769 SLS clients aged15years diagnosed between March 2016 and March 2018, matched by urban and rural settings of diagnosis, were selected for the study. CommLink counselors recorded resolved and unresolved barriers to care (e.g., perceived wellbeing, fear of partner response, stigmatization) during a median of 52days (interquartile range: 35-69) of case management. RESULTS: Twice as many CommLink than SLS clients initiated ART by 90days of diagnosis overall (88.4% vs. 37.9%, adjusted relative risk (aRR): 2.33, 95% confidence interval (CI): 1.97, 2.77) and during test and treat when all PLHIV were eligible for ART (96.2% vs. 37.1%, aRR: 2.59, 95% CI: 2.20, 3.04). By 18months of diagnosis, 54% more CommLink than SLS clients were initiated and retained on ART (76.3% vs. 49.5%, aRR: 1.54, 95% CI: 1.33, 1.79). Peer counselors helped resolve 896 (65%) of 1372 identified barriers of CommLink clients. Compared with clients with3 unresolved barriers to care, 42% (aRR: 1.42, 95% CI: 1.19, 1.68) more clients with 1-2 unresolved barriers, 44% (aRR: 1.44, 95% CI: 1.25, 1.66) more clients with all barriers resolved, and 54% (aRR: 1.54, 95% CI: 1.30, 1.81) more clients who had no identified barriers were initiated and retained on ART by 18months of diagnosis. CONCLUSIONS: To improve early ART initiation and retention among PLHIV diagnosed in community settings, HIV prevention programs should consider providing a package of peer-delivered linkage case management and treatment navigation services. Clients with multiple unresolved barriers to care measured as part of that package should be triaged for differentiated linkage and retention services. |
Recruitment of Patients With Amyotrophic Lateral Sclerosis for Clinical Trials and Epidemiological Studies: Descriptive Study of the National ALS Registry's Research Notification Mechanism
Mehta P , Raymond J , Han MK , Larson T , Berry JD , Paganoni S , Mitsumoto H , Bedlack RS , Horton DK . J Med Internet Res 2021 23 (12) e28021 BACKGROUND: Researchers face challenges in patient recruitment, especially for rare, fatal diseases such as amyotrophic lateral sclerosis (ALS). These challenges include obtaining sufficient statistical power as well as meeting eligibility requirements such as age, sex, and study proximity. Similarly, persons with ALS (PALS) face difficulty finding and enrolling in research studies for which they are eligible. OBJECTIVE: The aim of this study was to describe how the federal Agency for Toxic Substances and Disease Registry's (ATSDR) National ALS Registry is linking PALS to scientists who are conducting research, clinical trials, and epidemiological studies. METHODS: Through the Registry's online research notification mechanism (RNM), PALS can elect to be notified about new research opportunities. This mechanism allows researchers to upload a standardized application outlining their study design and objectives, and proof of Institutional Review Board approval. If the application is approved, ATSDR queries the Registry for PALS meeting the study's specific eligibility criteria, and then distributes the researcher's study material and contact information to PALS via email. PALS then need to contact the researcher directly to take part in any research. Such an approach allows ATSDR to protect the confidentiality of Registry enrollees. RESULTS: From 2013 to 2019, a total of 46 institutions around the United States and abroad have leveraged this tool and over 600,000 emails have been sent, resulting in over 2000 patients conservatively recruited for clinical trials and epidemiological studies. Patients between the ages of 60 and 69 had the highest level of participation, whereas those between the ages of 18 and 39 and aged over 80 had the lowest. More males participated (4170/7030, 59.32%) than females (2860/7030, 40.68%). CONCLUSIONS: The National ALS Registry's RNM benefits PALS by connecting them to appropriate ALS research. Simultaneously, the system benefits researchers by expediting recruitment, increasing sample size, and efficiently identifying PALS meeting specific eligibility requirements. As more researchers learn about and use this mechanism, both PALS and researchers can hasten research and expand trial options for PALS. |
Forced sexual initiation and early sexual debut and associated risk factors and health problems among adolescent girls and young women - Violence Against Children and Youth Surveys, Nine PEPFAR Countries, 2007-2018
Howard AL , Pals S , Walker B , Benevides R , Massetti GM , Oluoch RP , Ogbanufe O , Marcelin LH , Cela T , Mapoma CC , Gonese E , Msungama W , Magesa D , Kayange A , Galloway K , Apondi R , Wasula L , Mugurungi O , Ncube G , Sikanyiti I , Hamela J , Kihwele GV , Nzuza-Motsa N , Saul J , Patel P . MMWR Morb Mortal Wkly Rep 2021 70 (47) 1629-1634 Adolescent girls and young women aged 13-24 years are disproportionately affected by HIV in sub-Saharan Africa (1), resulting from biologic, behavioral, and structural* factors, including violence. Girls in sub-Saharan Africa also experience sexual violence at higher rates than do boys (2), and women who experience intimate partner violence have 1.3-2.0 times the odds of acquiring HIV infection, compared with those who do not (3). Violence Against Children and Youth Survey (VACS) data during 2007-2018 from nine countries funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) were analyzed to estimate prevalence and assess factors associated with early sexual debut and forced sexual initiation.(†) Among adolescent girls and young women aged 13-24 years who ever had sex, the prevalence of lifetime sexual violence ranged from 12.5% to 49.3%, and forced sexual initiation ranged from 14.7% to 38.9%; early sexual debut among adolescent girls and young women aged 16-24 years ranged from 14.4% to 40.1%. In multiple logistic regression models, forced sexual initiation was associated with being unmarried, violence victimization, risky sexual behaviors, sexually transmitted infections (STIs), and poor mental health. Early sexual debut was associated with lower education, marriage, ever witnessing parental intimate partner violence during childhood, risky sexual behaviors, poor mental health, and less HIV testing. Comprehensive violence and HIV prevention programming is needed to delay sexual debut and protect adolescent girls and young women from forced sex. |
Prevalence of advanced HIV disease, cryptococcal antigenemia and suboptimal clinical outcomes among those enrolled in care in Vietnam
Dat VQ , Lyss S , Hoai Dung NT , Hung LM , Pals SL , Van Anh HT , Van Kinh N , Bateganya M . J Acquir Immune Defic Syndr 2021 88 (5) 487-496 BACKGROUND: People living with advanced HIV disease (AHD) are at high risk of morbidity and mortality. We assessed the prevalence of cryptococcal antigenemia (CrAg) and clinical outcomes among patients newly presenting with CD4 ≤100 cells/μL in Vietnam. SETTING: Twenty-two public HIV clinics in Vietnam. METHODS: During August 2015-March 2017, ART-naïve adults presenting for care with CD4 ≤100 cells/μL were screened for CrAg. Those who consented to study enrollment were followed for up to 12 months and assessed for clinical outcomes. RESULTS: Of 3,504 patients with CD4 results, 1,354 (38.6%) had CD4 ≤100 cells/μL, of whom 1,177 (86.9%) enrolled in the study. Median age was 35 years (interquartile range 30-40); 872 (74.1%) were male, and 892 (75.8%) had CD4 <50 cells/μL. Thirty-six (3.1%) were CrAg positive. Overall 1,151 (97.8%) including all who were CrAg positive initiated ART. Of 881 (76.5%) followed for ≥12 months, 623 (70.7%) were still alive and on ART at 12 months, 54 (6.1%) had transferred to non-study clinics, 86 (9.8%) were lost to follow up (LTFU), and 104 (11.8%) had died. Among all 1,177 study participants, 143 (12.1%) died, most (123, 86.0%) before or within 6 months of enrollment. Twenty-seven (18.9%) died from pulmonary tuberculosis, 23 (16.1%) from extrapulmonary tuberculosis, 8 (5.6%) from Talaromyces marneffei infection, and 6 (4.2%) from opioid overdose. Eight deaths (5.8%) occurred among the 36 CrAg positive individuals. CONCLUSIONS: Late presentation for HIV care was common. The high mortality after entry in care calls for strengthening of the management of AHD. |
Monitoring emerging HIV drug resistance in sub-Saharan Africa in the era of dolutegravir.
da Silva J , Pals S , Chang J , Hackett S , Godfrey C , Raizes E . J Infect Dis 2021 225 (3) 364-366 Dolutegravir-based regimens are now standard of care for HIV treatment for millions of people around Sub-Saharan Africa. To ensure its continued efficacy, monitoring of emerging drug resistance that inform a treatment strategy amongst those failing is crucial. Here we outline the plan by the President Emergence Plan for AIDS Relief to leverage viral load infra structure to implement effective drug resistance surveillance in the countries it supports. |
Annual home-based HIV testing in the Chkw Health Demographic Surveillance System, Mozambique, 2014 to 2019: serial population-based survey evaluation
MacKellar D , Thompson R , Nelson R , Casavant I , Pals S , Bonzela J , Jaramillo A , Cardoso J , Ujamaa D , Tamele S , Chivurre V , Malimane I , Pathmanathan I , Heitzinger K , Wei S , Couto A , Vergara A . J Int AIDS Soc 2021 24 (7) e25762 INTRODUCTION: WHO recommends implementing a mix of community and facility testing strategies to diagnose 95% of persons living with HIV (PLHIV). In Mozambique, a country with an estimated 506,000 undiagnosed PLHIV, use of home-based HIV testing services (HBHTS) to help achieve the 95% target has not been evaluated. METHODS: HBHTS was provided at 20,000 households in the Chókwè Health Demographic Surveillance System (CHDSS), Mozambique, in annual rounds (R) during 2014 to 2019. Trends in prevalence of HIV infection, prior HIV diagnosis among PLHIV (diagnostic coverage), and undiagnosed HIV infection were assessed with three population-based surveys conducted in R1 (04/2014 to 04/2015), R3 (03/2016 to 12/2016), and R5 (04/2018 to 03/2019) of residents aged 15 to 59 years. Counts of patients aged ≥15 years tested for HIV in CHDSS healthcare facilities were obtained from routine reports. RESULTS: During 2014 to 2019, counsellors conducted 92,512 home-based HIV tests and newly diagnosed 3711 residents aged 15 to 59 years. Prevalence of HIV infection was stable (R1, 25.1%; R3 23.6%; R5 22.9%; p-value, 0.19). After the first two rounds (44,825 home-based tests; 31,717 facility-based tests), diagnostic coverage increased from 73.8% (95% CI 70.3 to 77.2) in R1 to 93.0% (95% CI 91.3 to 94.7) in R3, and prevalence of undiagnosed HIV infection decreased from 6.6% (95% CI 5.6 to 7.5) in R1 to 1.7% (95% CI 1.2 to 2.1) in R3. After two more rounds (32,226 home-based tests; 46,003 facility-based tests), diagnostic coverage was 95.4% (95% CI 93.7 to 97.1) and prevalence of undiagnosed HIV infection was 1.1% (95% CI 0.7 to 1.5) in R5. Prevalence of having last tested at home was 12.7% (95% CI 11.3 to 14.0) in R1, 45.2% (95% CI 43.4 to 47.0) in R3, and 41.4% (95% CI 39.5 to 43.2) in R5, and prevalence of having last tested at a healthcare facility was 45.3% (95% CI 43.3 to 47.3) in R1, 40.1% (95% CI 38.4 to 41.8) in R3, and 45.2% (95% CI 43.3 to 47.0) in R5. CONCLUSIONS: HBHTS successfully augmented facility-based testing to achieve HIV diagnostic coverage in a high-burden community of Mozambique. HBHTS should be considered in sub-Saharan Africa communities striving to diagnose 95% of persons living with HIV. |
Prevalence of Voluntary Medical Male Circumcision for HIV Infection Prevention - Chkw District, Mozambique, 2014-2019
Hines JZ , Thompson R , Toledo C , Nelson R , Casavant I , Pals S , Canda M , Bonzela J , Jaramillo A , Cardoso J , Ujamaa D , Tamele S , Chivurre V , Malimane I , Pathmanathan I , Heitzinger K , Wei S , Couto A , Come J , Vergara A , MacKellar D . MMWR Morb Mortal Wkly Rep 2021 70 (26) 942-946 Male circumcision is an important preventive strategy that confers lifelong partial protection (approximately 60% reduced risk) against heterosexually acquired HIV infection among males (1). In Mozambique, the prevalence of male circumcision was 51% when the voluntary medical male circumcision (VMMC) program began in 2009. The Mozambique Ministry of Health set a goal of 80% circumcision prevalence among males aged 10-49 years by 2019 (2). CDC analyzed data from five cross-sectional surveys of the Chókwè Health and Demographic Surveillance System (CHDSS) to evaluate progress toward the goal and guide ongoing needs for VMMC in Mozambique. During 2014-2019, circumcision prevalence among males aged 15-59 years increased 42%, from 50.1% to 73.5% (adjusted prevalence ratio [aPR] = 1.42). By 2019, circumcision prevalence among males aged 15-24 years was 90.2%, exceeding the national goal (2). However, circumcision prevalence among males in older age groups remained below 80%; prevalence was 62.7%, 54.5%, and 55.7% among males aged 25-34, 35-44, and 45-59 years, respectively. A multifaceted strategy addressing concerns about the safety of the procedure, cultural norms, and competing priorities that lead to lack of time could help overcome barriers to circumcision among males aged ≥25 years. |
Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.
Bachanas P , Alwano MG , Lebelonyane R , Block L , Behel S , Raizes E , Ussery G , Wang H , Ussery F , Pretorius Holme M , Sexton C , Pals S , Lasry A , Del Castillo L , Hader S , Lockman S , Bock N , Moore J . PLoS One 2021 16 (4) e0250211 INTRODUCTION: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study. METHODS: BCPP was designed to evaluate the impact of prevention interventions on HIV incidence in 30 communities in Botswana. We followed a longitudinal cohort of newly identified and known HIV-positive persons not on antiretroviral therapy (ART) identified through community-based testing activities through BCPP and referred with appointments to local HIV clinics in 15 intervention communities. Those who did not keep the first or follow-up appointments were tracked and traced through phone and home contacts. Improvements to service delivery models in the intervention clinics were also implemented. RESULTS: A total of 3,657 newly identified or HIV-positive persons not on ART were identified and referred to their local HIV clinic; 90% (3,282/3,657) linked to care and of those, 93% (3,066/3,282) initiated treatment. Near the end of the study, 221 persons remained >90 days late for appointments or missing. Tracing efforts identified 54/3,066 (2%) persons who initiated treatment but died, and 106/3,066 (3%) persons were located and returned to treatment. At study end, 61/3,066 (2%) persons remained missing and were never reached. Overall, 2,951 (98%) persons living with HIV (PLHIV) who initiated treatment were still alive, retained in care and still receiving ART out of the 3,001 persons alive at the end of the study. Of those on ART, 2,854 (97%) had current VL results and 2,784 (98%) of those were virally suppressed at study end. CONCLUSIONS: This study achieved high rates of linkage, treatment initiation, retention and VL coverage and suppression in a cohort of newly identified and known PLHIV not on ART. Tracking and tracing interventions effectively identified those persons who needed more resource intensive follow-up. The interventions implemented to improve service delivery and data quality may have also contributed to high linkage and retention rates. Clinical trial number: NCT01965470. |
HIV incidence by male circumcision status from the population-based HIV impact assessment (PHIA) surveys-eight sub-Saharan African countries, 2015-2017
Hines JZ , Sachathep K , Pals S , Davis SM , Toledo C , Bronson M , Parekh B , Carrasco M , Xaba S , Mandisarisa J , Kamobyi R , Chituwo O , Kirungi WL , Alamo S , Kabuye G , Awor AC , Mmbando S , Simbeye D , Aupokolo MA , Zemburuka B , Nyirenda R , Msungama W , Tarumbiswa T , Manda R , Nuwagaba-Biribonwoha H , Kiggundu V , Thomas AG , Watts H , Voetsch AC , Williams DB . J Acquir Immune Defic Syndr 2021 87 S89-S96 BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually-acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally-representative samples. Data from the Population-based HIV Impact Assessments (PHIAs) were used to compare incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from PHIAs conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia and Zimbabwe from 2015-2017. Incidence was measured using a recent infection testing algorithm, and analyzed by self-reported MC status distinguishing between medical and non-medical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random effects logistic regression model using pooled survey weights. Analyses were age-stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men (0.04% [95% CI: 0.00, 0.10%] versus 0.34% [95% CI: 0.10, 0.57%], respectively; p-value = 0.01); whereas among men 35-59 years, there was no significant incidence difference (1.36% [95% CI: 0.32, 2.39%] versus 0.55% [95% CI: 0.14, 0.67%], respectively; p-value = 0.14). DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally-representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa. |
High coverage of antiretroviral treatment with annual home-based HIV testing, follow-up linkage services, and implementation of test and start: Findings from the Chkw Health Demographic Surveillance System, Mozambique, 2014-2019
Pathmanathan I , Nelson R , de Louvado A , Thompson R , Pals S , Casavant I , Antonio Cardoso MJ , Ujamaa D , Bonzela J , Mikusova S , Chivurre V , Tamele S , Sleeman K , Zhang G , Zeh C , Dobbs T , Vubil A , Auld A , Briggs-Hagen M , Vergara A , Couto A , MacKellar D . J Acquir Immune Defic Syndr 2020 86 (4) e97-e105 BACKGROUND: Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counselling (HBHTC) and linkage services have been provided through the Chókwè Health and Demographic Surveillance System (CHDSS) for residents testing HIV-positive in this high HIV-burden district. METHODS: District-wide Test and Start (T&S, ART for all people living with HIV [PLHIV]) began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (VLS; <1000 viral RNA copies/mL). RESULTS: Between R1 (April 2014-April 2015) and R5 (April 2018-Mar 2019), 46,090 (67.2%) of 68,620 residents aged 15-59 years were tested for HIV at home at least once, and 3,711 were newly diagnosed with HIV and provided linkage services. Population prevalence of current ART use among PLHIV increased from 65.0% to 87.5% between R1 and R5. ART population prevalence was lowest among men aged 25-34 (67.8%) and women 15-24 (78.0%) years, and highest among women aged 35-44 (93.6%) and 45-59 years (93.7%) in R5. VLS prevalence increased among all PLHIV aged 15-59 years from 52.0% in R1 to 78.3% in R5. DISCUSSION: Between 2014 and 2019, CHDSS residents surpassed the UNAIDS targets of 81% of PLHIV on ART and of those, ≥73% virally suppressed. This achievement supports the combination of efforts from HBHTC, support for linkage to care and treatment, and continued investments in T&S implementation. |
Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort study
Auld AF , Fielding K , Agizew T , Maida A , Mathoma A , Boyd R , Date A , Pals SL , Bicego G , Liu Y , Shiraishi RW , Ehrenkranz P , Serumola C , Mathebula U , Alexander H , Charalambous S , Emerson C , Rankgoane-Pono G , Pono P , Finlay A , Shepherd JC , Holmes C , Ellerbrock TV , Grant AD . BMC Med 2020 18 (1) 311 BACKGROUND: Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 < 200/μL or WHO stage III/IV. METHODS: We used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC. RESULTS: Among 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/μL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA. |
Community-wide HIV testing, linkage case management, and defaulter tracing in Bukoba, Tanzania: pre-intervention and post-intervention, population-based survey evaluation
Steiner C , MacKellar D , Cham HJ , Rwabiyago OE , Maruyama H , Msumi O , Pals S , Weber R , Kundi G , Byrd J , Kazaura K , Madevu-Matson C , Morales F , Justman J , Rutachunzibwa T , Rwebembera A . Lancet HIV 2020 7 (10) e699-e710 BACKGROUND: Community randomised trials have had mixed success in implementing combination prevention strategies that diagnose 90% of people living with HIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression in 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council, Tanzania, by scaling up new HIV testing, linkage, and retention interventions. METHOD: We did population-based, cross-sectional surveys before and after our community-wide intervention in Bukoba-a mixed urban and rural council of approximately 150 000 residents located on the western shore of Lake Victoria in Tanzania. BCPE interventions were implemented in 11 government-supported health-care facilities throughout Bukoba from Oct 1, 2014, to March 31, 2017, when national ART-eligibility guidelines expanded from CD4 counts of less than 350 cells per μL (Oct 1, 2014-Dec 31, 2015) and 500 or less cells per μL (Jan 1, 2016-Sept 30, 2016) to any CD4 cell count (test and treat, Oct 1, 2016-March 31, 2017). We used pre-intervention (Nov 4, 2013-Jan 25, 2014) and post-intervention (June 21, 2017-Sept 20, 2017) population-based household surveys to assess population prevalence of undiagnosed HIV infection and ART coverage, and progress towards 90-90-90, among residents aged 18-49 years. FINDINGS: During the 2·5-year intervention, BCPE did 133 695 HIV tests, diagnosed and linked 3918 people living with HIV to HIV care at 11 Bukoba facilities, and returned to HIV care 604 patients who had stopped care. 4795 and 5067 residents aged 18-49 years participated in pre-intervention and post-intervention surveys. HIV prevalence before and after the intervention was similar: pre-intervention 8·9% (95% CI 7·5-10·4); post-intervention 8·4% (6·9-9·9). Prevalence of undiagnosed HIV infection decreased from 4·7% to 2·0% (prevalence ratio 0·42, 95% CI 0·31-0·57), and current ART use among all people living with HIV increased from 32·2% to 70·9% (2·20, 1·82-2·66) overall, 23·0% to 62·1% among men (2·70, 1·84-3·96), and 16·7% to 64·4% among people aged 18-29 years (3·87, 2·54-5·89). Of 436 and 435 people living with HIV aged 18-49 years who participated in pre-intervention and post-intervention surveys, previous HIV diagnosis increased from 47·4% (41·3-53·4) to 76·2% (71·8-80·6), ART use among diagnosed people living with HIV increased from 68·0% (60·9-75·2) to 93·1% (90·2-96·0), and viral load suppression of those on ART increased from 88·7% (83·6-93·8) to 91·3% (88·6-94·1). INTERPRETATION: BCPE findings suggest scaling up recommended HIV testing, linkage, and retention interventions can help reduce prevalence of undiagnosed HIV infection, increase ART use among all people living with HIV, and make substantial progress towards achieving 90-90-90 in a relatively short period. BCPE facility-based testing and linkage interventions are undergoing national scale up to help achieve 90-90-90 in Tanzania. FUNDING: US Presidents' Emergency Plan for AIDS Relief. |
Drug resistance mutations among South African children living with HIV on WHO-recommended ART regimens.
Hackett S , Teasdale CA , Pals S , Muttiti A , Mogashoa M , Chang J , Zeh C , Ramos A , Rivadeneira ED , DeVos J , Sleeman K , Abrams EJ . Clin Infect Dis 2020 73 (7) e2217-e2225 BACKGROUND: Children living with HIV (CLHIV) receiving antiretroviral treatment (ART) in resource limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate WHO-recommended first-line regimens. We report data from a cohort of ART-naïve South African children who initiated first-line ART. METHODS: ART-eligible CLHIV aged 0-12 years were enrolled from 2012 to 2014 at five public South African facilities and followed for up to 24 months. Enrolled CLHIV received standard of care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing. RESULTS: Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were <3 years and all CLHIV on ABC/3TC/EFV were ≥3 years. Overall, 80.6% (58/72) had at least one drug resistance mutation (DRM). DRMs to NNRTIs and NRTIs were found among 65% and 51% of all CLHIV, respectively, with no statistical difference by ART regimen. More CLHIV on ABC/3TC/EFV, 47.8% (11/23), were found to have 0 or only 1 effective antiretroviral drug remaining in their current regimen compared to 8.2% (4/49) on ABC/3TC/LPV/r. CONCLUSIONS: High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed PMTCT interventions on DRMs. However, drug susceptibility analysis, reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least two effective agents on their current HIV regimen than those on ABC/3TC/EFV. |
Tuberculosis preventive treatment opportunities at antiretroviral therapy initiation and follow-up visits
Agizew T , Surie D , Oeltmann JE , Letebele M , Pals S , Mathebula U , Mathoma A , Kassa M , Hamda S , Pono P , Rankgoane-Pono G , Boyd R , Auld A , Finlay A . Public Health Action 2020 10 (2) 64-69 Setting: Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%. Objectives: To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV. Design: A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the Xpert((R)) MTB/RIF Package Rollout Evaluation Study between 2012 and 2015. Results: Of 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4 <200 cells/mm(3) (aOR = 1.4, P = 0.030); anemia (aOR = 2.39, P < 0.001); cough (aOR = 11.21, P < 0.001); fever (aOR = 2.15, P = 0.001); and weight loss (aOR = 2.60, P = 0.002). Conclusion: Eligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana. |
Outcomes of HIV-positive patients with non-tuberculous mycobacteria positive culture who received anti-tuberculous treatment in Botswana: Implications of using diagnostic algorithms without non-tuberculous mycobacteria
Agizew T , Boyd R , Mathebula U , Mathoma A , Basotli J , Serumola C , Pals S , Finlay A , Lekone P , Rankgoane-Pono G , Tlhakanelo T , Chihota V , Auld AF . PLoS One 2020 15 (6) e0234646 BACKGROUND: Patients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert(R) MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures. METHODS: PLHIV attending one of the 22 participating HIV clinics, who screened positive for >/=1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment. RESULTS: Among 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated 'no MTB'. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher's exact test p = 1.00. CONCLUSIONS: While the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential. |
Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial
Wirth KE , Gaolathe T , Pretorius Holme M , Mmalane M , Kadima E , Chakalisa U , Manyake K , Matildah Mbikiwa A , Simon SV , Letlhogile R , Mukokomani K , van Widenfelt E , Moyo S , Bennett K , Leidner J , Powis KM , Lebelonyane R , Alwano MG , Jarvis J , Dryden-Peterson SL , Kgathi C , Moore J , Bachanas P , Raizes E , Abrams W , Block L , Sento B , Novitsky V , El-Halabi S , Marukutira T , Mills LA , Sexton C , Pals S , Shapiro RL , Wang R , Lei Q , DeGruttola V , Makhema J , Essex M , Lockman S , Tchetgen Tchetgen EJ . Lancet HIV 2020 7 (6) e422-e433 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. |
Improving sputum collection processes to increase tuberculosis case finding among HIV-positive persons in Botswana
Mathebula U , Emerson C , Agizew T , Pals S , Boyd R , Mathoma A , Basotli J , Rankgoane-Pono G , Serumola C , Date A , Auld AF , Finlay A . Public Health Action 2020 10 (1) 11-16 Setting: Twenty-two human immunodeficiency virus (HIV) clinics in Botswana. Objective: To compare sputum collection rates, sputum quality and volume, and tuberculosis (TB) diagnosis rates before and after field efforts to improve sputum collection among individuals newly diagnosed with HIV with TB symptoms. Design: Newly diagnosed individuals living with HIV attending 22 HIV clinics in Botswana were screened for TB from August 2012 to March 2014. Starting in May 2013, a field intervention composed of the introduction of a tracking log for presumed TB patients, and patient instructions and sputum induction to improve sputum collection rates was implemented. Results: Prior to the intervention, sputum collection rates were 44.1% (384/870). Subsequently, sputum collection increased to 58.3% (579/993) (P < 0.001). Sputum quality and volume also improved. Although rates of TB diagnosis increased from 9.7% (84/870) to 12.5% (120/993), this difference was not significant (P = 0.143). Conclusion: Sputum collection rates among presumptive TB cases, as well as sputum quality and volume improved after implementation of the field intervention. To improve sputum collection rates, efforts at the program level should be ongoing. |
Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial
Auld AF , Agizew T , Mathoma A , Boyd R , Date A , Pals SL , Serumola C , Mathebula U , Alexander H , Ellerbrock TV , Rankgoane-Pono G , Pono P , Shepherd JC , Fielding K , Grant AD , Finlay A . BMC Med 2020 18 (1) 19 BACKGROUND: Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality. METHODS: At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation. RESULTS: We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/muL in SOC, 246/muL in EC, and 241/muL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees. CONCLUSIONS: Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed. TRIAL REGISTRATION: Retrospectively registered: ClinicalTrials.gov (NCT02538952). |
Assessment of routine screening of pediatric contacts of adults with tuberculosis disease in Tanzania
Emerson C , Ng'eno B , Ngowi B , Pals S , Kohi W , Godwin M , Date A , Modi S . Public Health Action 2019 9 (4) 148-152 Setting: Ten selected healthcare facilities in Tanzania, March-April 2016. Objective(s): To assess the implementation of screening among pediatric contacts of adults with tuberculosis (TB) disease. Design(s): Using a mixed-methods approach, we conducted a questionnaire study among sputum smear-positive adult TB patients and abstracted data from their patient cards to assess the implementation of a child contact management (CCM) intervention. We also conducted in-depth interviews with healthcare workers (HCWs) to solicit their views on clinical practices and challenges in CCM. Result(s): A total of 141 adult smear-positive TB patients reported 396 children living in households; detailed information on 346 (87.4%) was available. Only 37 (10.7%) children were clinically assessed for TB, 5 (13.5%) were diagnosed with TB, and 22 started on isoniazid preventive therapy (IPT) (59.0%). Of the 320 children whose caregivers responded to whether their children had undergone human immunodeficiency virus (HIV) testing, 55 (17.2%) had been tested and one (1.8%) was HIV-positive. Forty-one HCWs described passive CCM without use of contact or IPT registers. Conclusion(s): We identified gaps in the implementation of TB screening, IPT provision, and HIV testing in pediatric contacts of adults with sputum smear-positive TB. Systematic efforts, including increasing HCW training and educating the community, may improve implementation. |
Tuberculosis treatment outcomes among people living with HIV diagnosed using Xpert MTB/RIF versus sputum-smear microscopy in Botswana: a stepped-wedge cluster randomised trial
Agizew T , Chihota V , Nyirenda S , Tedla Z , Auld AF , Mathebula U , Mathoma A , Boyd R , Date A , Pals SL , Lekone P , Finlay A . BMC Infect Dis 2019 19 (1) 1058 BACKGROUND: Xpert(R) MTB/RIF (Xpert) has high sensitivity for diagnosing tuberculosis (TB) compared to sputum-smear microscopy (smear) and can reduce time-to-diagnosis, time-to-treatment and potentially unfavorable patient-level treatment outcome. METHODS: People living with HIV (PLHIV) initiating antiretroviral therapy at 22 HIV clinics were enrolled and underwent systematic screening for TB (August 2012-November 2014). GeneXpert instruments were deployed following a stepped-wedge design at 13 centers from October 2012-June 2013. Treatment outcomes classified as an unfavorable outcome (died, treatment failure or loss-to-follow-up) or favorable outcome (cured and treatment completed). To determine outcome, smear was performed at month 5 or 6. Empiric treatment was defined as initiating treatment without/before receiving TB-positive results. Adjusting for intra-facility correlation, we compared patient-level treatment outcomes between patients screened using smear (smear arm)- and Xpert-based algorithms (Xpert arm). RESULTS: Among 6041 patients enrolled (smear arm, 1816; Xpert arm, 4225), 256 (199 per 2985 and 57 per 1582 person-years of follow-up in Xpert and smear arms, respectively; adjusted incidence rate ratio, 9.07; 95% confidence interval [CI]: 4.70-17.48; p < 0.001) received TB diagnosis and were treated. TB treatment outcomes were available for 203 patients (79.3%; Xpert, 157; smear, 46). Unfavorable outcomes were reported for 21.7% (10/46) in the smear and 13.4% (21/157) in Xpert arm (adjusted hazard ratio, 1.40; 95% CI: 0.75-2.26; p = 0.268). Compared to smear, in Xpert arm median days from sputum collection to TB treatment was 6 days (interquartile range [IQR] 2-17 versus 22 days [IQR] 3-51), p = 0.005; patients with available sputum test result had microbiologically confirmed TB in 59.0% (102/173) versus 41.9% (18/43), adjusted Odds Ratio [aOR], 2.00, 95% CI: 1.01-3.96, p = 0.048). In smear arm empiric treatment was 68.4% (39/57) versus 48.7% (97/199), aOR, 2.28, 95% CI: 1.24-4.20, p = 0.011), compared to Xpert arm. CONCLUSIONS: TB treatment outcomes were similar between the smear and Xpert arms. However, compared to the smear arm, more patients in the Xpert arm received a TB diagnosis, had a microbiologically confirmed TB, and had a shorter time-to-treatment, and had a lower empiric treatment. Further research is recommended to identify potential gaps in the Botswana health system and similar settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02538952. Retrospectively registered on 2 September 2015. |
The effect of sputum quality and volume on the yield of bacteriologically-confirmed tb by xpert mtb/rif and smear
Zimba O , Tamuhla T , Basotli J , Letsibogo G , Pals S , Mathebula U , Mathoma A , Serumola C , Ramogale K , Boyd R , Tran T , Finlay A , Auld A , Date A , Alexander H , Chihota V , Agizew T . Pan Afr Med J 2019 33 110 Introduction: the World Health Organization endorsed (2010) the use of Xpert MTB/RIF and countries are shifting from smear microscopy (smear)-based to Xpert MTB/RIF-based tuberculosis (TB) diagnostic algorithms. As with smear, sputum quality may predict the likelihood of obtaining a bacteriologically-confirmed TB when using Xpert MTB/RIF. Methods: from 08/12-11/2014, all people living with HIV were recruited at 22 clinics. For patients screened positive using the four TB symptoms their sputa were tested by Xpert MTB/RIF and smear. Laboratorians assessed and recorded sputum appearance and volume. The yield of bacteriologically-positive sputum evaluated using Xpert MTB/RIF and smear, likelihood-ratios were calculated. Results: among 6,041 patients enrolled 2,296 were presumptive TB, 1,305 (56.8%) had > 1 sputa collected and 644/1,305 (49.3%) had both Xpert MTB/RIF and smear results. Since >1 sputa collected from 644 patients 954 sputa were tested by Xpert MTB/RIF and smear. Bacteriologically-positive sputum was two-fold higher with Xpert MTB/RIF 11.4% versus smear 5.3%, p < 0.001. Sputum appearance and quantity were not predictive of bacteriologically-positive results, except volume of 2ml to < 3ml, tested by Xpert MTB/RIF LR+= 1.26 (95% CI, 1.05–1.50). Conclusion: Xpert MTB/RIF test yield to bacteriologically-positive sputum was superior to smear. Sputum quality and quantity, however, were not consistently predictive of bacteriologically-positive results by Xpert MTB/RIF or smear. |
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