Loss to follow-up and opportunities for reengagement in HIV care in rural Mozambique: A prospective cohort study.

Patients lost to follow-up (LTFU) over the human immunodeficiency virus (HIV) cascade have poor clinical outcomes and contribute to onward HIV transmission. We assessed true care outcomes and factors associated with successful reengagement in patients LTFU in southern Mozambique.Newly diagnosed HIV-positive adults were consecutively recruited in the Manhiça District. Patients LTFU within 12 months after HIV diagnosis were visited at home from June 2015 to July 2016 and interviewed for ascertainment of outcomes and reasons for LTFU. Factors associated with reengagement in care within 90 days after the home visit were analyzed by Cox proportional hazards model.Among 1122 newly HIV-diagnosed adults, 691 (61.6%) were identified as LTFU. Of those, 557 (80.6%) were approached at their homes and 321 (57.6%) found at home. Over 50% had died or migrated, 10% had been misclassified as LTFU, and 252 (78.5%) were interviewed. Following the visit, 79 (31.3%) reengaged in care. Having registered in care and a shorter time between LTFU and visit were associated with reengagement in multivariate analyses: adjusted hazards ratio of 3.54 [95% confidence interval (CI): 1.81-6.92; P < .001] and 0.93 (95% CI: 0.87-1.00; P = .045), respectively. The most frequently reported barriers were the lack of trust in the HIV-diagnosis, the perception of being in good health, and fear of being badly treated by health personnel and differed by type of LTFU.Estimates of LTFU in rural areas of sub-Saharan Africa are likely to be overestimated in the absence of active tracing strategies. Home visits are resource-intensive but useful strategies for reengagement for at least one-third of LTFU patients when applied in the context of differentiated care for those LTFU individuals who had already enrolled in HIV care at some point.

Loss to follow-up and opportunities for reengagement in HIV care in rural Mozambique. A prospective cohort study

Patients lost to follow-up (LTFU) over the human immunodeficiency virus (HIV) cascade have poor clinical outcomes and contribute to onward HIV transmission. We assessed true care outcomes and factors associated with successful reengagement in patients LTFU in southern Mozambique. Newly diagnosed HIV-positive adults were consecutively recruited in the Manhiça District. Patients LTFU within 12 months after HIV diagnosis were visited at home from June 2015 to July 2016 and interviewed for ascertainment of outcomes and reasons for LTFU. Factors associated with reengagement in care within 90 days after the home visit were analyzed by Cox proportional hazards model. Among 1122 newly HIV-diagnosed adults, 691 (61.6%) were identified as LTFU. Of those, 557 (80.6%) were approached at their homes and 321 (57.6%) found at home. Over 50% had died or migrated, 10% had been misclassified as LTFU, and 252 (78.5%) were interviewed. Following the visit, 79 (31.3%) reengaged in care. Having registered in care and a shorter time between LTFU and visit were associated with reengagement in multivariate analyses: adjusted hazards ratio of 3.54 [95% confidence interval (CI): 1.81­ 6.92; P<.001] and 0.93 (95% CI: 0.87­1.00; P=.045), respectively. The most frequently reported barriers were the lack of trust in the HIV-diagnosis, the perception of being in good health, and fear of being badly treated by health personnel and differed by type of LTFU. Estimates of LTFU in rural areas of sub-Saharan Africa are likely to be overestimated in the absence of active tracing strategies. Home visits are resource-intensive but useful strategies for reengagement for at least one-third of LTFU patients when applied in the context of differentiated care for those LTFU individuals who had already enrolled in HIV care at some point.

Compromise of Second-Line Antiretroviral Therapy Due to High Rates of Human Immunodeficiency Virus Drug Resistance in Mozambican Treatment-Experienced Children With Virologic Failure.

BACKGROUND: Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. METHODS: Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with ≥1000 copies/mL were genotyped. RESULTS: Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. CONCLUSION: This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings.

Performance characteristics of finger-stick dried blood spots (DBS) on the determination of human immunodeficiency virus (HIV) treatment failure in a pediatric population in Mozambique.

Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott's VL test with a paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing.

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/µL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

A Decade of Antiretroviral Therapy Scale-up in Mozambique: Evaluation of Outcome Trends and New Models of Service Delivery Among More Than 300,000 Patients Enrolled During 2004-2013.

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.

Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women - 12 Countries, 2002-2013.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Temporal Trends in Patient Characteristics and Outcomes Among Children Enrolled in Mozambique's National Antiretroviral Therapy Program

During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. Methods: Rates of death, loss to follow-up (LTFU) and attrition (death or LTFU) were evaluated in a nationally representative sample of 1054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. Results: At ART initiation during 2004-2009, 50% were male; median age was 3.3 years; median CD4% was 13%; median CD4 count was 375 cells/µL; median weight-for-age Z score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (P = 0.001); median time from care to ART declined from 93 to 62 days (P = 0.004); the percentage aged <2 at ART initiation increased from 16% to 48% (P = 0.021); the percentage of patients with prior tuberculosis declined from 50% to 10% (P = 0.009); and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (P < 0.001). Over 2652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall but increased from 3% to 22% during 2004-2009, mainly because of increases in 12-month LTFU (from 3% to 18%). Conclusion: Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

Temporal Trends in Patient Characteristics and Outcomes Among Children Enrolled in Mozambique's National Antiretroviral Therapy Program.

BACKGROUND: During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. METHODS: Rates of death, loss to follow-up (LTFU) and attrition (death or LTFU) were evaluated in a nationally representative sample of 1054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. RESULTS: At ART initiation during 2004-2009, 50% were male; median age was 3.3 years; median CD4% was 13%; median CD4 count was 375 cells/µL; median weight-for-age Z score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (P = 0.001); median time from care to ART declined from 93 to 62 days (P = 0.004); the percentage aged <2 at ART initiation increased from 16% to 48% (P = 0.021); the percentage of patients with prior tuberculosis declined from 50% to 10% (P = 0.009); and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (P < 0.001). Over 2652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall but increased from 3% to 22% during 2004-2009, mainly because of increases in 12-month LTFU (from 3% to 18%). CONCLUSION: Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

Antiretroviral therapy enrollment characteristics and outcomes among HIV-infected adolescents and young adults compared with older adults--seven African countries, 2004-2013.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

Incidence and determinants of tuberculosis among adults initiating antiretroviral therapy--Mozambique, 2004-2008.

BACKGROUND: In Mozambique, tuberculosis (TB) is thought to be the most common cause of death among antiretroviral therapy (ART) enrollees. Monitoring proportions of enrollees screened for TB, and incidence and determinants of TB during ART can help clinicians and program managers identify program improvement opportunities. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study among a nationally representative sample of the 79,500 adults (>14 years old) initiating ART during 2004-2007 to estimate clinician compliance with TB screening guidelines, factors associated with active TB at ART initiation, and incidence and predictors of documented TB during ART follow-up. Of 94 sites enrolling >50 adults on ART, 30 were selected using probability-proportional-to-size sampling; 2,596 medical records at these sites were randomly selected for abstraction and analysis. At ART initiation, median age of patients was 34, 62% were female, median baseline CD4(+) T-cell count was 153/µL, and 11% were taking TB treatment. Proportions of records with TB screening documentation before ART initiation improved from 31% to 66% during 2004-2007 (p<0.001). TB screening compliance varied widely by ART clinic [n = 30, 2%-98% (p<0.001)] and supporting non-Governmental Organization (NGO) [n = 7, 27%-83% (p<0.001)]. Receiving TB treatment at ART enrollment was associated with male sex (p<0.001), weight <45 kg (p<0.001) and CD4<50/µL (p = 0.001). Isoniazid preventive therapy (IPT) was prescribed to <1% of ART enrollees not taking TB treatment. TB incidence during ART was 2.32 cases per 100 person-years. Factors associated with TB incidence included adherence to ART <95% (AHR 2.06; 95% CI, 1.32-3.21). CONCLUSION: Variations in TB screening by clinic and NGO may reflect differing investments in TB screening activities. Future scale-up should target under-performing clinics. Scale-up of TB screening at ART initiation, IPT, and ART adherence interventions could significantly reduce incident TB during ART.

Four-year treatment outcomes of adult patients enrolled in Mozambique's rapidly expanding antiretroviral therapy program.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.