Harriet Nuwagaba-Biribonwoha

Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania

BackgroundIn Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.MethodsIn September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety- six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves.ResultsFrom October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative.ConclusionsThe EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.

Advanced HIV Disease at Entry into HIV Care and Initiation of Antiretroviral Therapy During 2006–2011: Findings From Four Sub-Saharan African Countries

BACKGROUND Timely antiretroviral therapy (ART) initiation requires early diagnosis of human immunodeficiency virus (HIV) infection with prompt enrollment and engagement in HIV care. METHODS We examined programmatic data on 334 557 adults enrolling in HIV care, including 149 032 who initiated ART during 2006-2011 at 132 facilities in Kenya, Mozambique, Rwanda, and Tanzania. We examined trends in advanced HIV disease (CD4+ count <100 cells/μL or World Health Organization disease stage IV) and determinants of advanced HIV disease at ART initiation. RESULTS Between 2006-2011, the median CD4+ count at ART initiation increased from 125 to 185 cells/μL an increase of 10 cells/year. Although the proportion of patients initiating ART with advanced HIV disease decreased from 42% to 29%, sex disparities widened. In 2011, the odds of advanced disease at ART initiation were higher among men (adjusted odds ratio [AOR], 1.4; 95% CI, 1.3-1.5), those on tuberculosis treatment (AOR, 1.6; 95% CI, 1.3-2.0), and those with a ≥ 12 month gap in pre-ART care (AOR, 2.0; 95% CI, 1.6-2.6). CONCLUSIONS Intensified efforts are needed to identify and link HIV-infected individuals to care earlier and to retain them in continuous pre-ART care to facilitate more timely ART initiation.

High attrition before and after ART initiation among youth (15-24 years of age) enrolled in HIV care.

Objectives:To compare pre and post-ART attrition between youth (15–24 years) and other patients in HIV care, and to investigate factors associated with attrition among youth. Design:Cohort study utilizing routinely collected patient-level data from 160 HIV clinics in Kenya, Mozambique, Tanzania, and Rwanda. Methods:Patients at least 10 years of age enrolling in HIV care between 01/05 and 09/10 were included. Attrition (loss to follow-up or death 1 year after enrollment or ART initiation) was compared between youth and other patients using multivariate competing risk (pre-ART) and traditional (post-ART) Cox proportional hazards methods accounting for within-clinic correlation. Among youth, patient-level and clinic-level factors associated with attrition were similarly assessed. Results:A total of 312 335 patients at least 10 years of age enrolled in HIV care; 147 936 (47%) initiated ART, 17% enrolling in care and 10% initiating ART were youth. Attrition before and after ART initiation was substantially higher among youth compared with other age groups. Among youth, nonpregnant women experienced lower pre-ART attrition than men [sub-division hazard ratio = 0.90, 95% confidence interval (CI): 0.86–0.94], while both pregnant [adjusted hazard ratio (AHR) = 0.85, 95% CI: 0.74–0.97] and nonpregnant (AHR = 0.79, 95% CI: 0.73–0.86) female youth experienced lower post-ART attrition than men. Youth attending clinics providing sexual and reproductive health services including condoms (AHR = 0.47, 95% CI: 0.32–0.70) and clinics offering adolescent support groups (AHR = 0.73, 95% CI: 0.52–1.0) experienced significantly lower attrition after ART initiation. Conclusion:Youth experienced substantially higher attrition before and after ART initiation compared with younger adolescents and older adults. Adolescent-friendly services were associated with reduced attrition among youth, particularly after ART initiation.

High Levels of Adherence and Viral Suppression in a Nationally Representative Sample of HIV-Infected Adults on Antiretroviral Therapy for 6, 12 and 18 Months in Rwanda

Background Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART) in Africa. Methods We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL) measurements. Multivariable logistic regression examined predictors of non-perfect (<100%) 30-day adherence and detectable VL (>40 copies/ml). Results Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months); younger age; reporting severe (vs. no or few) side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL); alcohol use; and attending sites which initiated ART services in 2003–2004 and 2005 (vs. 2006–2007); sites with ≥600 (vs. <600 patients) on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. Conclusions High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.

The Problem of Late ART Initiation in Sub-Saharan Africa: A Transient Aspect of Scale-up or a Long-term Phenomenon?

Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic.

Strategies for more effective monitoring and evaluation systems in HIV programmatic scale-up in resource-limited settings: Implications for health systems strengthening.

Program monitoring and evaluation (M&E) has the potential to be a cornerstone of health systems strengthening and of evidence-informed implementation and scale-up of HIV-related services in resource-limited settings. We discuss common challenges to M&E systems used in the rapid scale-up of HIV services as well as innovations that may have relevance to systems used to monitor, evaluate, and inform health systems strengthening. These include (1) Web-based applications with decentralized data entry and real-time access to summary reporting; (2) timely feedback of information to site and district staff; (3) site-level integration of traditionally siloed program area indicators; (4) longitudinal tracking of program and site characteristics; (5) geographic information systems; and (6) use of routinely collected aggregate data for epidemiologic analysis and operations research. Although conventionally used in the context of vertical programs, these approaches can form a foundation on which data relevant to other health services and systems can be layered, including prevention services, primary care, maternal-child health, and chronic disease management. Guiding principles for sustainable national M&E systems include country-led development and ownership, support for national programs and policies, interoperability, and employment of an open-source approach to software development.

Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique

Background Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. Methods To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation. Results The proportion of patients initiating ART late decreased from 46% to 37% during 2005–2007, but remained constant (between 37–33%) from 2007–2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AORfemale_not_pregnant_vs._male = 0.66, 95%CI [0.62–0.69]; AORpregnant_vs._non_pregnant = 0.60, 95%CI [0.49–0.73]), younger and older age (AOR15–25_vs.26–30 = 0.86, 95%CI [0.79–0.94], AOR>45_vs.26–30 = 0.72, 95%CI [0.67–0.77]), entry into care via PMTCT (AORentry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35–0.50]), marital status (AORmarried/in union_vs.single = 0.87, 95%CI [0.83–0.92]), education (AORsecondary_or_higher_vs.primary = 0.87, 95%CI [0.83–0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AORCD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74–0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77–0.93]). Conclusion: The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.

Disclosure, Knowledge of Partner Status, and Condom Use Among HIV-Positive Patients Attending Clinical Care in Tanzania, Kenya, and Namibia

We describe the frequency of and factors associated with disclosure, knowledge of partners HIV status, and consistent condom use among 3538 HIV-positive patients attending eighteen HIV care and treatment clinics in Kenya, Namibia, and Tanzania. Overall, 42% of patients were male, and 64% were on antiretroviral treatment. The majority (80%) had disclosed their HIV status to their partners, 64% knew their partners HIV status, and 77% reported consistent condom use. Of those who knew their partners status, 18% reported their partner was HIV negative. Compared to men, women were significantly less likely to report disclosing their HIV status to their sex partner(s), to knowing their partners HIV status, and to using condoms consistently with HIV-negative partners. Other factors negatively associated with consistent condom use include nondisclosure, alcohol use, reporting a casual sex partner, and desiring a pregnancy. Health care providers should target additional risk reduction counseling and support services to patients who report these characteristics.

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

Background Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs. Methods We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART. Results 31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation. Conclusions Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.

Advanced disease at enrollment in HIV care in four sub-Saharan African countries: change from 2006 to 2011 and multilevel predictors in 2011.

Objectives:To examine changes between 2006 and 2011 in the proportion of HIV-positive patients newly enrolled in HIV care with advanced disease and the median CD4+ cell count at enrollment; and identify patient, facility, and contextual-level factors associated with late enrollment in care in 2011. Design:Cross-sectional over time. Methods:For time-trends analyses, routinely collected patient-level data (307 110 adults newly enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46 201 in 195 facilities), and facility and population-level survey data were used. Late enrollment was defined as CD4+ cell count 350 cells/&mgr;l or less and/or WHO clinical stage 3/4. Results:Late enrollment declined from 69.9 to 57.2% (P < 0.0001); median CD4+ cell count increased from 242 to 292 cells/&mgr;l (Ptrend < 0.0001). In 2011, risk of late enrollment was significantly higher for men and nonpregnant women vs. pregnant women; patients aged above 25 vs. 15–25 years; nonmarried vs. married; and those entering from sites other than prevention of mother-to-child transmission. More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. Conclusions:Despite improvement, in 2011, 57% of patients entered HIV care who were already antiretroviral therapy-eligible. The lower risk of late enrollment among those referred from prevention of mother-to-child transmission and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care.