Maria Lahuerta

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.

Pregnancy desires, and contraceptive knowledge and use among prevention of mother-to-child transmission clients in Rwanda.

Objective:To understand pregnancy intentions and contraception knowledge and use among HIV-positive and negative women in the national prevention of mother-to-child transmission (PMTCT) program in Rwanda. Design:A cross-sectional survey of 236 HIV-positive and 162 HIV-negative postpartum women interviewed within 12 months of their expected delivery date in 12 randomly selected public-sector health facilities providing PMTCT services. Methods:Bivariate analyses explored fertility intentions, and family planning knowledge and use by HIV status. Multivariate analysis identified socio-demographic and service delivery-related predictors of reporting a desire for additional children and modern family planning use. Results:HIV-positive women were less likely to report wanting additional children than HIV-negative women (8 vs. 49%, P < 0.001), and although a majority of women reported discussing family planning with a health worker during their last pregnancy (HIV-positive 79% vs. HIV-negative 69%, P = 0.057), modern family planning use remained low in both groups (HIV-positive 43% vs. HIV-negative 12%, P < 0.001). Condoms were the most commonly used method among HIV-positive women (31%), whereas withdrawal was most frequently reported among HIV-negative women (19%). In multivariate analysis, HIV-negative women were 16 times more likely to report wanting additional children and nearly 85% less likely to use modern family planning. Women who reported making two or less antenatal care visits were 77% less likely to use modern family planning. Conclusion:Our results highlight success in provision of family planning counseling in PMTCT services in Rwanda. As family planning use was low among HIV-positive and negative women, further efforts are needed to improve uptake of modern methods, including dual protection, in Rwandan PMTCT settings.

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.

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.

Comparison of users of an HIV/syphilis screening community-based mobile van and traditional voluntary counselling and testing sites in Guatemala.

Objectives The use of a mobile van (MV) for screening for HIV and other sexually transmitted infections (STIs) is effective at reaching at-risk populations. The aim of this study was to compare behaviour characteristics and HIV and syphilis prevalence between subjects tested at a MV offering voluntary counselling and testing and those tested at three STI clinics in Guatemala. Methods Over 28 months, female sex workers (FSWs), men who have sex with men/transgenders (MSM/TG), and people not reporting being a member of a risk group (NR) were offered HIV and syphilis rapid tests and interviewed about their sociodemographic and risk behaviour. Results 2874 subjects were tested (MV, 1336 (46%); clinics, 1538 (54%)). The MV screened 73% of FSWs and 73% of the MSM/TG, and detected 19% of HIV and 69% of syphilis cases. HIV prevalence was significantly higher (p<0.001) at the STI clinics than at the MV for both NR and MSM/TG groups (NR, 7% vs 1%; MSM/TG, 8% vs 1%, respectively). A significantly higher proportion of MSM/TG screened at the STI clinic reported having had a prior HIV test (MV, 21%; clinics, 41%; p<0.001), whereas more FSWs tested in the MV reported having multiple partners and using condoms during their last sexual intercourse. Conclusions The higher prevalence of HIV and syphilis at the STI clinics suggests that they successfully identified high-risk subjects. In particular, the NR group showed higher than expected HIV and syphilis prevalence. Innovative approaches such as the use of a MV helped to increase access to other hard-to-reach groups such as MSM/TG and FSWs.

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.

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique

Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well‐characterized.

A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study

BackgroundDespite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from “real-life” settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum.Methods/DesignWe are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions—including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care—as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted.DiscussionStudy findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a “real-life” service delivery system in a SSA country severely impacted by HIV.Trial registrationClinicaltrials.gov, NCT01930084

High retention among HIV-infected children in Rwanda during scale-up and decentralization of HIV Care and treatment programs 2004 to 2010

Background: Efforts to scale-up HIV treatment in high burden countries have resulted in wider access to care, improved survival and decreased morbidity for HIV-infected children. The country of Rwanda has made significant achievements in expanding coverage of pediatric HIV services. Methods: We describe the extent of and factors associated with mortality and lost to follow-up (LTF) in children (<15 years) enrolled in HIV care at 39 ICAP-supported facilities across Rwanda from 2004 to 2010 by antiretroviral treatment (ART) status. We estimated the 1-year cumulative incidence of death and LTF among all children enrolled in care (pre-ART) and children on ART. Survival analysis was used to evaluate factors associated with death and LTF in both groups. Results: Between January 2004 and June 2010, 3244 children with a median age of 5.7 years (interquartile range 2.8–9.6) enrolled in HIV care. One-year cumulative incidence for death and LTF among pre-ART children was 4% (95% confidence interval [CI]: 3–5%) and 5% (95% CI: 4–6%), respectively. Overall, 2035 (63%) children initiated ART, median age 6.3 years (interquartile range 3.3–10.4): 1-year Kaplan–Meier estimates of death and LTF were 3% (95% CI: 3–4%) and 1% (95% CI: 1–2%), respectively. Factors associated with an increased hazard for death among pre-ART children included being <18 months old versus ≥5 years (adjusted sub hazard ratio [aSHR] = 4.4, 95% CI: 2.9–6.8) and World Health Organization stage IV versus I (aSHR = 4.1, 95% CI: 2.0–8.4), whereas children entering care through prevention of mother-to-child transmission had lower hazard than those from voluntary counseling and testing (aSHR = 0.50, 95% CI: 0.25–1.0). Markers of advanced disease, including severe immunosuppression (aSHR = 0.25, 95% CI: 0.12–0.54), and enrollment in care in rural versus urban clinics (aSHR = 0.71, 95% CI: 0.53–0.97) were protective against LTF. For children on ART, factors associated with hazard of death included younger age (adjusted hazard ratio [aHR] <18 months versus ≥5 years = 2.1, 95% CI: 1.3–3.6), severe malnutrition versus not malnourished (aHR = 3.2, 95% CI: 1.3–8.1), advanced World Health Organization stage (aHR IV versus I = 9.8, 95% CI: 3.5–27.4) and severe immunodeficiency versus no evidence (aHR = 2.3, 95% CI: 1.7–3.3). No associations were observed with LTF among children on ART. Conclusions: The results demonstrate very high retention among children enrolled in HIV care in Rwanda. Younger children continue to be particularly vulnerable, underscoring the urgent need for early identification, rapid treatment initiation and long-term retention in care.