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.

Mozambique's Community Antiretroviral Therapy Support Group Program: The Role of Social Relationships in Facilitating HIV/AIDS Treatment Retention.

The Community Antiretroviral (ARV) Therapy Support Group (CASG) program aims to address low retention rates in Mozambique's HIV treatment program and the absorptive capacity of the country's health facilities. CASG provides patients with the opportunity to form groups, whose members provide peer support and collect ARV medications on a rotating basis for one another. Based on the promising results in one province, a multi-site level evaluation followed. We report on qualitative findings from this evaluation from the patient perspective on the role of social relationships (as facilitated through CASG) in conferring time, financial, educational and psychosocial benefits that contribute to improved patient retention. These findings may be helpful in informing what aspects of social relationships are critical to foster as CASG is implemented within a greater number of Mozambican health facilities, and as other countries design and implement related models of care and treatment with a support group component.

The effect of a performance-based financing program on HIV and maternal/child health services in Mozambique-an impact evaluation.

Performance-based financing (PBF) is a mechanism by which health providers are paid on the basis of outputs or results delivered. A PBF program was implemented on the provision of HIV, prevention of mother-to child HIV transmission (PMTCT), and maternal/child health (MCH) services in two provinces of Mozambique. A retrospective case-control study design was used in which PBF provinces were matched with control provinces to evaluate the impact of PBF on 18 indicators. Due to regional heterogeneity, we evaluated the intervention sites (North and South) separately. Beginning January 2011, 11 quarters (33 months or 2.75 years) of data from 134 facilities after matching (84 in the North and 50 in the South) were used. Our econometric framework employed a multi-period, multi-group difference-in-differences model on data that was matched using propensity scoring. The regression design employed a generalized linear mixed model with both fixed and random effects, fitted using the seemingly unrelated regression technique. PBF resulted in positive impacts on MCH, PMTCT and paediatric HIV program outcomes. The majority of the 18 indicators responded to PBF (77% in the North and 66% in the South), with at least half of the indicators demonstrating a statistically significant increase in average output of more than 50% relative to baseline. Excluding pregnant women, the majority of adult HIV treatment indicators did not respond to PBF. On average, it took 18 months (six quarters) of implementation for PBF to take effect, and impact was generally sustained thereafter. Indicators were not sensitive to price, but were inversely correlated to the level of effort associated with marginal output. No negative impacts on incentivized indicators nor spill-over effects on non-incentivized indicators were observed. The PBF program in Mozambique has produced large, sustained increases in the provision of PMTCT, paediatric HIV and MCH services. Our results demonstrate that PBF is an effective strategy for driving down the HIV epidemic and advancing MCH care service delivery as compared with input financing alone.

Correction: Community ART Support Groups in Mozambique: The Potential of Patients as Partners in Care.

[This corrects the article DOI: 10.1371/journal.pone.0166444.].

Community ART Support Groups in Mozambique: The Potential of Patients as Partners in Care.

BACKGROUND: High rates of attrition are stymying Mozambique's national HIV Program's efforts to achieve 80% treatment coverage. In response, Mozambique implemented a national pilot of Community Adherence and Support Groups (CASG). CASG is a model in which antiretroviral therapy (ART) patients form groups of up to six patients. On a rotating basis one CASG group member collects ART medications at the health facility for all group members, and distributes those medications to the other members in the community. Patients also visit their health facility bi-annually to receive clinical services. METHODS: A matched retrospective cohort study was implemented using routinely collected patient-level data in 68 health facilities with electronic data systems and CASG programs. A total of 129,938 adult ART patients were registered in those facilities. Of the 129,938 patients on ART, 6,760 were CASG members. A propensity score matched analysis was performed to assess differences in mortality and loss to follow-up (LTFU) between matched CASG and non-CASG members. Propensity scores were estimated using a random-effects logistic regression model. The following covariates where included in the model: sex, educational status, WHO stage, year of ART initiation, age, CASG eligibility, CD4 cell count category, weight, and employment status. RESULTS: Non-CASG participants had higher LTFU rates (HR 2.356; p = 0.04) than matched CASG participants; however, there were no significant mortality differences between CASG and non-CASG participants. Compared with the full cohort of non-CASG members, CASG members were more likely to be female (74% vs. 68%), tended to have a lower median CD4 counts at ART initiation (183 cells/m3 vs. 200cells/m3) and be less likely to have a secondary school education (15% vs. 23%). CONCLUSION: ART patients enrolled in CASG were significantly less likely to be LTFU compared to matched patients who did not join CASG. CASG appears to be an effective strategy to decrease LTFU in Mozambique's national ART program.

Outcomes Among Children Enrolled in HIV Care in Mozambique 2009-2013.

BACKGROUND: Scale-up of HIV care and antiretroviral therapy (ART) services for children has expanded access, but significant gaps and challenges remain. We examined lost to follow-up (LTF) and mortality in a large cohort of children enrolled in HIV care in Mozambique. METHODS: Routinely collected medical data on children 0-14 years enrolled in care 2009-2013 at ICAP-supported health facilities in 5 provinces of Mozambique were used. Children not receiving ART (pre-ART) were considered LTF if they did not a have a visit within 12 months of the end of data collection; for those receiving ART, LTF was no visit within 6 months. Competing risk and Kaplan-Meier estimators were used, respectively, to estimate pre-ART and on ART LTF and mortality. RESULTS: A total of 13,695 children enrolled in HIV care at 64 health facilities (48.6%, <2 years), and 7733 (56.5%) initiated ART during follow-up. Cumulative incidence of pre-ART LTF was 32.9% [95% confidence interval (CI): 32.1-33.7] and 34.4% (95% CI: 33.6-35.2) by 12 and 24 months, respectively, and was highest in children <5 years (12-month LTF in children 2-4 years, 34.2%, 95% CI: 32.6-35.9). Pre-ART mortality at 12 months was 3.3% (95% CI: 3.0-3.6) and was highest in children <2 years (4.1%, 95% CI: 3.6-4.6). On ART, LTF was 28.6% (95% CI: 27.6-29.7) and 37.6 (95% CI: 36.4-38.8) at 12 and 24 months, and 12 months mortality after ART was 8.0% (95% CI: 7.3-8.7). CONCLUSIONS: High rates of LTF were observed in this large cohort of HIV-infected children accessing care in Mozambique both before and after ART initiation highlighting the urgent need for interventions to improve retention in routine care settings.

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.

Barriers to health care in rural Mozambique: a rapid ethnographic assessment of planned mobile health clinics for ART.

BACKGROUND: In Mozambique, 1.6 million people are living with HIV, and over 60% of the population lives in rural areas lacking access to health services. Mobile health clinics, implemented in 2013 in 2 provinces, are beginning to offer antiretroviral therapy (ART) and basic primary care services. Prior to introduction of the mobile health clinics in the communities, we performed a rapid ethnographic assessment to understand barriers to accessing HIV care and treatment services and acceptability and potential use of the mobile health clinics as an alternative means of service delivery. METHODS: We conducted assessments in Gaza province in January 2013 and in Zambezia Province in April-May 2013 in districts where mobile health clinic implementation was planned. Community leaders served as key informants, and chain-referral sampling was used to recruit participants. Interviews were conducted with community leaders, health care providers, traditional healers, national health system patients, and traditional healer patients. Interviewees were asked about barriers to health services and about mobile health clinic acceptance. RESULTS: In-depth interviews were conducted with 117 participants (Gaza province, n = 57; Zambezia Province, n = 60). Barriers to accessing health services included transportation and distance-related issues (reliability, cost, and travel time). Participants reported concurrent use of traditional and national health systems. The decision to use a particular health system depended on illness type, service distance, and lack of confidence in the national health system. Overall, participants were receptive to using mobile health clinics for their health care and ability to increase access to ART. Hesitations concerning mobile health clinics included potentially long wait times due to high patient loads. Participants emphasized the importance of regular and published visit schedules and inclusion of community members in planning mobile health clinic services. CONCLUSION: Mobile health clinics can address many barriers to uptake of HIV services, particularly related to transportation issues. Involvement of community leaders, providers, traditional healers, and patients, as well as regularly scheduled mobile clinic visits, are critical to successful service delivery implementation in rural areas.

Barriers to Health Care in Rural Mozambique: A Rapid Ethnographic Assessment of Planned Mobile Health Clinics for ART

Background: In Mozambique, 1.6 million people are living with HIV, and over 60% of the population lives in rural areas lacking access to health services. Mobile health clinics, implemented in 2013 in 2 provinces, are beginning to offer antiretroviral therapy (ART) and basic primary care services. Prior to introduction of the mobile health clinics in the communities, we performed a rapid ethnographic assessment to understand barriers to accessing HIV care and treatment services and acceptability and potential use of the mobile health clinics as an alternative means of service delivery. Methods: We conducted assessments in Gaza province in January 2013 and in Zambezia Province in April­May 2013 in districts where mobile health clinic implementation was planned. Community leaders served as key informants, and chain-referral sampling was used to recruit participants. Interviews were conducted with community leaders, health care providers, traditional healers, national health system patients, and traditional healer patients. Interviewees were asked about barriers to health services and about mobile health clinic acceptance. Results: In-depth interviews were conducted with 117 participants (Gaza province, n557; Zambezia Province, n560). Barriers to accessing health services included transportation and distance-related issues (reliability, cost, and travel time). Participants reported concurrent use of traditional and national health systems. The decision to use a particular health system depended on illness type, service distance, and lack of confidence in the national health system. Overall, participants were receptive to using mobile health clinics for their health care and ability to increase access to ART. Hesitations concerning mobile health clinics included potentially long wait times due to high patient loads. Participants emphasized the importance of regular and published visit schedules and inclusion of community members in planning mobile health clinic services. Conclusion: Mobile health clinics can address many barriers to uptake of HIV services, particularly related to transportation issues. Involvement of community leaders, providers, traditional healers, and patients, as well as regularly scheduled mobile clinic visits, are critical to successful service delivery implementation in rural areas.

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.

Predictors for mortality and loss to follow-up among children receiving anti-retroviral therapy in Lilongwe, Malawi.

OBJECTIVES: To determine predictors of mortality in children on anti-retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi. METHODS: Retrospective case cohort study by chart review of children who had started ART between October 2004 and May 2006. Bivariable and multivariable analysis were performed with and without defaulters to evaluate associations according to vital status and to identify independent predictors of mortality. RESULTS: Forty-one of 258 children (15.9%) were deceased, 185 (71.7%) were alive, and 32 (12.4%) had defaulted: 51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age. Most were WHO stage III or IV (56% and 37%, respectively). On multivariate analysis, factors most strongly associated with mortality and defaulting were age <18 months [hazards ratio (HR) 2.11 (95% CI 1.0-4.51)] and WHO stage IV [HR 2.00 (95% CI 1.07-3.76)]. CONCLUSIONS: To improve outcomes of HIV-positive children, they must be identified and treated early, specifically children under 18 months of age. Access to infant diagnostic procedures must be improved to allow effective initiation of ART in infants at higher risk of death.