Andrew F. Auld

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.

Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania Uganda and Zambia.

Objectives:To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design:A cross-sectional study. Methods:Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results:A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion:Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients.

Retention and risk factors for attrition among adults in antiretroviral treatment programmes in Tanzania, Uganda and Zambia

We assessed retention and predictors of attrition (recorded death or loss to follow‐up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia.

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. Presidents 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.

Trends and determinants of survival for over 200 000 patients on antiretroviral treatment in the Botswana National Program: 2002–2013

Objectives:To determine the incidence and risk factors of mortality for all HIV-infected patients receiving antiretroviral treatment at public and private healthcare facilities in the Botswana National HIV/AIDS Treatment Programme. Design:We studied routinely collected data from 226 030 patients enrolled in the Botswana National HIV/AIDS Treatment Programme from 2002 to 2013. Methods:A person-years (P-Y) approach was used to analyse all-cause mortality and follow-up rates for all HIV-infected individuals with documented antiretroviral therapy initiation dates. Marginal structural modelling was utilized to determine the effect of treatment on survival for those with documented drug regimens. Sensitivity analyses were performed to assess the robustness of our results. Results:Median follow-up time was 37 months (interquartile range 11–75). Mortality was highest during the first 3 months after treatment initiation at 11.79 (95% confidence interval 11.49–12.11) deaths per 100 P-Y, but dropped to 1.01 (95% confidence interval 0.98–1.04) deaths per 100 P-Y after the first year of treatment. Twelve-month mortality declined from 7 to 2% of initiates during 2002–2012. Tenofovir was associated with lower mortality than stavudine and zidovudine. Conclusion:The observed mortality rates have been declining over time; however, mortality in the first year, particularly first 3 months of antiretroviral treatment, remains a distinct problem. This analysis showed lower mortality with regimens containing tenofovir compared with zidovudine and stavudine. CD4+ cell count less than 100 cells/&mgr;l, older age and being male were associated with higher odds of mortality.

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.

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania, Uganda, and Zambia

Objectives To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence. Methods Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months. Results Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms. Conclusions Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.

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.

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/&mgr;L). 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/&mgr;L 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.

Temporal Trends in Mortality and Loss to Follow-Up among Children Enrolled in Côte d'Ivoire's National Antiretroviral Therapy Program

Background: During 2004–2008, >2000 children (<15 years old) initiated antiretroviral therapy (ART) in Côte d’Ivoire. Nationally representative outcomes, temporal trends in outcomes during 2004–2008 and site-level outcome determinants have not been investigated. Methods: Incidence rates of death, loss to follow-up (LTFU) and attrition (death or LTFU) were evaluated in a nationally representative, retrospective cohort study among 2,110 children, who initiated ART at 29 facilities in Côte d’Ivoire during 2004–2008. Results: At ART initiation, 54% were male, 1% was HIV-2-infected and median age was 5.1 years. Median CD4% was 11%, and 61% had weight-for-age Z-score (WAZ) ⩽−2. Vaccination completion was documented for 9% of children. Eleven of 29 facilities had an integrated nutrition program. Over 4585 person-years of ART, 237 children died and 427 became LTFU. Twelve-month attrition was 22% overall, but increased from 4% to 34% during 2004–2008, due to increases in 12-month mortality (from 3–11%) and 12-month LTFU (from 2% to 23%). In adjusted analysis, compared with enrollees in 2004, enrollees in 2008 had nearly 4-fold higher mortality and 8-fold higher LTFU. World Health Organization stage III/IV, CD4% <10%, WAZ ⩽2 and hemoglobin <8 g/dL, were predictive of mortality. Incomplete vaccination was predictive of mortality and LTFU. Facilities with nutrition programs had lower LTFU and mortality rates. Clinics reporting nurse dissatisfaction with working conditions had higher LTFU rates. Conclusion: Investigation of causes of increasing mortality and LTFU is needed. Ensuring earlier ART initiation, vaccination completion, scale-up of site-level nutrition programs and nurse work-environment satisfaction, could improve pediatric ART program outcomes.