Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible ...PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes.
We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% 95% CI: 12%-55%) was significantly lower than among persons aged ≥15 years (72% 95% CI: 47%-89%; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% 95% CI: 49%-87%). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART.
Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With about 3.4 million HIV-infected persons, Nigeria has the second highest number of people living with HIV (PLHIV) in the world. However, antiretroviral treatment (ART) coverage in Nigeria remains ...low with only 748,846 (22%) of PLHIV on ART by the end of 2014. Retention of HIV-infected patients in pre-ART care is essential to ensure timely ART initiation. We assessed outcomes of patients enrolled in Nigeria's pre-ART program during 2004-2012.
We conducted a nationally representative retrospective cohort study among adults (≥15 years old), enrolling in pre-ART programs supported by the U.S. President's Emergency Plan for AIDS Relief in Nigeria. A total of 35 sites enrolling ≥50 patients in pre-ART were selected using probability proportional-to-size sampling; 2,415 eligible medical records at these sites were randomly selected for abstraction. Determinants of loss to follow-up (LTFU) and mortality during pre-ART care were estimated using Cox proportional hazards regression models.
The median age at enrollment was 32 years (interquartile range (IQR) 27-40). A total of 1,216 (51.4%) initiated ART by the time of data abstraction. Among the remaining 1,199 patients, 898 (74.9%) had been LTFU, 180 (15.0%) were alive and in pre-ART care, 71 (5.9%) had died, 50 (4.2%) had transferred out or stopped care. Baseline markers of advanced disease, including weight <45 kg (adjusted hazard ration (AHR) = 4.23; 95% confidence interval (CI): 1.51-15.58) and more advanced WHO disease stage, were predictive of pre-ART mortality. Compared with patients aged 15-24, patients aged 35-44 (AHR = 0.67; 95% CI: 1.0.47-0.95) and age 45-54 (AHR = 0.66; 95% CI: 0.48-0.91) had lower LTFU rates. Compared with attending facilities in North Central geopolitical zone, attending facility locations in South East (AHR = 0.44; 95% CI: 0.24-0.83) was protective against LTFU.
About half of patients enrolling in HIV program during 2004-2012 in Nigeria had not initiated ART by 2013. Key strategies to improve early ART initiation among pre-ART enrollees include implementation of the WHO test and treat guidelines, earlier HIV testing, and better monitoring to improve ART initiation rates. Further research to understand regional variations in pre-ART outcomes is warranted.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for ...co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported.
In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004-2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4(+) T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3-1.8, weight <45 kg (AHR 2.1; 95% CI, 1.6-2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively.
ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study evaluated the impact of a safe injection safety training on healthcare worker (HCW) practice and knowledge following an HIV outbreak in Roka commune, Cambodia.
Surveys were conducted at ...baseline (September 2016) and seven months after a training intervention (March 2018) using the World Health Organization standardized injection practices assessment tool. HCWs were sampled at 15 purposively government health facilities in two provinces. HCWs were observed during injection practices and interviewed by trained experts from Becton-Dickinson and the Ministry of Health Cambodia. The Rao-Scott chi square test was used test for differences between baseline and follow-up.
We completed 115 observations of practice at baseline and 206 at post-training follow-up. The proportion of patients whose identification was confirmed by HCWs prior to procedure being performed increased from 40.4% to 98% (p <0.0001). The proportion of HCWs who practiced correct hand hygiene increased from 22.0% to 80.6% (p = 0.056) therapeutic observations and 17.2% to 63.4% (p = 0.0012) diagnostic observations. Immediate disposal of sharps by HCWs decreased from 96.5% to 92.5% (p = 0.0030).
We found significant improvements in the practice of patient identity confirmation and hand hygiene but not in the immediate disposal of sharps in the post-training intervention. However, findings are not representative of all HCWs in the country. Further pre-service and in-service training and monitoring are necessary to ensure sustained behavior change.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Estimating HIV-1 incidence using biomarker assays in cross-sectional surveys is important for understanding the HIV pandemic. However, the utility of these estimates has been limited by uncertainty ...about what input parameters to use for false recency rate (FRR) and mean duration of recent infection (MDRI) after applying a recent infection testing algorithm (RITA).
This article shows how testing and diagnosis reduce both FRR and mean duration of recent infection compared to a treatment-naive population. A new method is proposed for calculating appropriate context-specific estimates of FRR and mean duration of recent infection. The result of this is a new formula for incidence that depends only on reference FRR and mean duration of recent infection parameters derived in an undiagnosed, treatment-naive, nonelite controller, non-AIDS-progressed population.
Applying the methodology to eleven cross-sectional surveys in Africa results in good agreement with previous incidence estimates, except in 2 countries with very high reported testing rates.
Incidence estimation equations can be adapted to account for the dynamics of treatment and recent infection testing algorithms. This provides a rigorous mathematical foundation for the application of HIV recency assays in cross-sectional surveys.
The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active ...tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia.
In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation.
We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training.
TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
To quantify the impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the risk of HIV transmission through infected blood donations in countries supported by PEPFAR blood ...safety programs.
Methods
Data reported to the World Health Organization Global Database on Blood Safety were analyzed from 28 countries in sub‐Saharan Africa (SSA), Asia, and the Caribbean during 2004‐2015. We used the Goals model of Spectrum Spectrum System Software, version 5.53, to perform the modeling, assuming laboratory quality for HIV testing had 91.9% sensitivity and 97.7% specificity irrespective of testing method based on results of two external quality assurance and proficiency testing studies of transfusion screening for HIV in SSA blood centers. We calculated the number of new HIV infections from the number of transfusions and the prevalence of HIV infection acquired from blood transfusions with infected blood donations. We determined the impact of laboratory testing programs by estimating the number of new HIV infections averted since PEPFAR implementation.
Results
Assuming that HIV testing would not be performed in any of these countries without PEPFAR funding, the number of new HIV infections acquired from blood transfusions averted by laboratory testing increased over time in all 28 countries. The total number of HIV infections averted was estimated at 229 278 out of 20 428 373 blood transfusions during 2004‐2015.
Conclusion
Our mathematical modeling suggests a positive impact achieved over 12 years of PEPFAR support for blood safety. Standardized HIV testing of donated blood has reduced the risk of HIV transmission through blood transfusions in SSA, Asia, and the Caribbean.
BACKGROUND:During 2004–2013 in Mozambique, 455,600 HIV-positive adults (≥15 years old) initiated antiretroviral therapy (ART). We evaluated trends in patient characteristics and outcomes during ...2004–2013, outcomes of universal treatment for pregnant women (Option B+) implemented since 2013, and effect on outcomes of distributing ART to stable patients through Community ART Support Groups (CASG) since 2010.
METHODS:Data for 306,335 adults starting ART during 2004–2013 at 170 ART facilities were analyzed. Mortality and loss to follow-up (LTFU) were estimated using competing risks models. Outcome determinants were estimated using proportional hazards models, including CASG participation as a time-varying covariate.
RESULTS:Compared with ART enrollees in 2004, enrollees in 2013 were more commonly female (55% vs. 73%), more commonly pregnant if female (<1% vs. 30%), and had a higher median baseline CD4 count (139 vs. 235/μL). During 2004–2013, observed 6-month mortality declined from 7% to 2% but LTFU increased from 24% to 30%. Pregnant women starting ART with CD4 count >350/μL and WHO stage I/II under Option B+ guidelines in 2013 had low 6-month mortality (0.1%) but high 6-month LTFU (38%). During 2010–2013, 6766 patients joined CASGs. In multivariable analysis, compared with nonparticipation in CASG, CASG participation was associated with 35% lower LTFU but similar mortality.
CONCLUSIONS:Initiation of ART at earlier disease stages in later calendar years might explain observed declines in mortality. Retention interventions are needed to address trends of increasing LTFU overall and the high LTFU among Option B+ pregnant women specifically. Further expansion of CASG could help reduce LTFU.
Diagnosis followed by effective treatment of tuberculosis (TB) reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum smear microscopy is widely used for diagnosis, despite ...limited sensitivity in PLHIV. Evidence is needed to determine the optimal diagnostic approach for these patients.
From May 2011 through June 2012, we recruited PLHIV from 15 HIV treatment centers in western Kenya. We collected up to three sputum specimens for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF (Xpert), and culture, regardless of symptoms. We calculated the incremental yield of each test, stratifying results by CD4 cell count and specimen type; data were analyzed to account for complex sampling.
From 778 enrolled patients, we identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified 25 (33.6%); Xpert identified those plus an additional 18 (incremental yield = 24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases; whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/μL and 30/45 (67.0%) of cases with CD4 counts ≥100 cells/μl.
In PLHIV, Xpert substantially increased diagnostic yield compared to smear microscopy and had the highest yield when used to test morning specimens and specimens from PLHIV with CD4 count <100 cells/μL. TB programs unable to replace smear microscopy with Xpert for all symptomatic PLHIV should consider targeted replacement and using morning specimens.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Estimating HIV incidence is essential to monitoring progress in sub-Saharan African nations toward global epidemic control. One method for incidence estimation is to test nationally representative ...samples using laboratory-based incidence assays. An alternative method based on reported HIV testing history and the proportion of undiagnosed infections has recently been described.
We applied an HIV incidence estimation method which uses history of testing to nationally representative cross-sectional survey data from 12 sub-Saharan African nations with varying country-specific HIV prevalence. We compared these estimates with those derived from laboratory-based incidence assays. Participants were tested for HIV using the national rapid test algorithm and asked about prior HIV testing, date and result of their most recent test, and date of antiretroviral therapy initiation.
The testing history-based method consistently produced results that are comparable and strongly correlated with estimates produced using a laboratory-based HIV incidence assay (ρ = 0.85). The testing history-based method produced incidence estimates that were more precise compared with the biomarker-based method. The testing history-based method identified sex-, age-, and geographic location-specific differences in incidence that were not detected using the biomarker-based method.
The testing history-based method estimates are more precise and can produce age-specific and sex-specific incidence estimates that are informative for programmatic decisions. The method also allows for comparisons of the HIV transmission rate and other components of HIV incidence among and within countries. The testing history-based method is a useful tool for estimating and validating HIV incidence from cross-sectional survey data.