Jens Levy

A Pilot Study of Food Supplementation to Improve Adherence to Antiretroviral Therapy Among Food-Insecure Adults in Lusaka, Zambia

Background:The provision of food supplementation to food-insecure patients initiating antiretroviral therapy (ART) may improve adherence to medications. Methods:A home-based adherence support program at 8 government clinics assessed patients for food insecurity. Four clinics provided food supplementation, and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics. Results:Between May 1, 2004, and March 31, 2005, 636 food- insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls (relative risk = 1.5; 95% confidence interval: 1.2 to 1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline World Health Organization stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response. Conclusions:This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.

Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia

Objective:To determine the population effectiveness of a city-wide perinatal HIV prevention program. Design:An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). Methods:All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother–infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. Results:Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother–infant pairs in the surveillance population received both a maternal and infant dose of NVP. Conclusions:Successful perinatal HIV prevention requires each mother–infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.

Community-based follow-up for late patients enrolled in a district-wide programme for antiretroviral therapy in Lusaka Zambia.

Abstract Timely adherence to clinical and pharmacy appointments is well correlated with favourable patient outcomes among HIV-infected individuals on antiretroviral therapy. To date, however, there is little work exploring reasons behind missed visits or evaluating programmatic strategies to recall patients. For this study we implemented community-based follow-up of late patients as part of a large-scale programme for HIV care and treatment in Lusaka, Zambia. Through a network of local home-based care organizations, we attempted home visits to recall patients using locator information provided at time of enrolment. Between May and September 2005, home-based caregivers were dispatched to trace 1,343 patients with missed appointments. Of these, 554 (41%) were untraceable because the provided address was invalid, the patient had moved or no one was at the home. Of the remaining 789, 359 (46%) were reported to have died. Only 430 (54% of those traced, 32% overall) were contacted directly and encouraged to return for care. The likelihood of patient return was higher among traced patients in crude analysis (relative risk [RR] = 2.5; 95%CI = 1.9–3.2) and in multivariable analysis controlling for baseline body mass index, sex and CD4 + count ≤ 50/µL (adjusted RR = 2.3; 95%CI = 1.7–3.2). However, the process was inefficient: one late patient returned for every 18 home visits that were made. Reasons for missed visits were provided in 271 of 430 (63%) of the patients who were successfully traced. Common reasons included feeling too sick to come to the clinic, travelling away from home and being too busy. Despite the availability of free ART in Lusaka, patients face significant barriers to attending scheduled clinical visits. Cost-effective and feasible strategies are urgently needed to improve timely patient follow-up.

Simple Adherence Assessments to Predict Virologic Failure among HIV-Infected Adults with Discordant Immunologic and Clinical Responses to Antiretroviral Therapy

We evaluated the association between two antiretroviral therapy (ART) adherence measurements--the medication possession ratio (MPR) and patient self-report--and detectable HIV viremia in the setting of rapid service scale-up in Lusaka, Zambia. Drug adherence and outcomes were assessed in a subset of patients suspected of treatment failure based on discordant clinical and immunologic responses to ART. A total of 913 patients were included in this analysis, with a median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had optimal adherence (MPR > or =95%), 306 (34%) had suboptimal adherence (MPR 80-94%), and 76 (8%) had poor adherence (MPR <80%). Of the 913 patients, 238 (26%) had VL > or =400 copies/ml when tested. When compared to individuals with optimal adherence, there was increasing risk for virologic failure in those with suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based on MPR. During the antiretroviral treatment course, 676 patients (74%) reported no missed doses. The proportion of patients with virologic failure did not differ significantly among those reporting any missed dose from those reporting perfect adherence (26% vs. 26%, p = 0.97). Among patients with suspected treatment failure, a lower MPR was associated with higher rates of detectable viremia. However, the suboptimal sensitivity and specificity of MPR limit its utility as a sole predictor of virologic failure.

Individual-Level Predictors for HIV Testing Among Antenatal Attendees in Lusaka, Zambia

Despite the availability of antiretroviral prophylaxis, roughly one-fifth of public-sector antenatal patients decline HIV testing in Lusaka, Zambia. We administered a survey to determine individual-level predictors of HIV testing. Of 1064 antenatal attendees approached after pretest counseling, 1060 (>99%) participated. Of these, 686 (65%) agreed to HIV testing. On bivariate analysis controlling for clinic of attendance, women younger than 20 years old (adjusted RR [ARR] = 1.14), unmarried (ARR = 1.14), pregnant for the first time (ARR = 1.14), with lower educational attainment (ARR = 1.15), and with lower income (ARR = 1.14) were all more likely to undergo testing. When HIV risk was considered, women with low self-perceived risk were most likely to undergo HIV testing. As risk perception increased, likelihood for testing decreased (P for trend < 0.001). Although not statistically predictive, we identified prevalent community beliefs that may act as barriers to testing. Because individual-level characteristics were only weakly predictive of HIV testing, future work should concentrate on community-level factors.

Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study

BACKGROUNDnAlthough generic anti-retroviral drugs are in common use throughout the developing world, studies comparing their clinical effectiveness with that of proprietary formulations are lacking.nnnMETHODSnWe analysed observational data from a large cohort of adults on anti-retroviral therapy (ART) to assess potential differences between generic and proprietary zidovudine (ZDV) formulations in post-90-day mortality, programme failure (a composite of death, follow-up losses and withdrawals) and other clinical outcomes. We accounted for drug exposure in three ways: an initial dispensation approach that categorized patients according to the first prescription; time-varying approach that attributed an outcome to the formulation taken at the time of event; and predominant exposure approach that considered only those with >75% exposure to either brand or generic ZDV. Proprietary formulations were used as the reference group in all adjusted Cox proportional hazard regressions.nnnRESULTSnAmong 14u2009736 patients eligible for analysis, 7277 (49%) initiated a generic formulation of ZDV and 7459 (51%) initiated a proprietary formulation. When categorized according to initial dispensation, no difference in post-90-day mortality was observed between the two groups [adjusted hazard ratio (AHR): 0.93, 95% confidence interval (CI): 0.77-1.12]. Similar findings were noted when drug formulation was treated as a time-varying exposure (AHR: 1.15, 95% CI: 0.89-1.48) when analysis was limited to those with a predominant exposure to one formulation or the other (AHR: 0.59, 95% CI: 0.24-1.49). Results were consistent across all approaches when programme failure was considered as an outcome. No longitudinal differences were detected between formulations for CD4 response, weight change and haemoglobin concentration. Generic ZDV formulations were associated with slight decreases in single-drug substitution.nnnCONCLUSIONSnIn this large programmatic cohort of adults starting ZDV-based first-line therapy, clinical outcomes appeared similar among patients on generic or proprietary formulations. These findings support continued use of generic anti-retroviral drug formulations in resource-constrained settings.

Methods and Baseline Results of a Repeated Cross-Sectional Survey to Assess the Public Health Impact of Antiretroviral Therapy in Lusaka, Zambia

Although the individual-level impact of antiretroviral therapy (ART) is well documented, there are few available data describing the public health impact of services for persons infected with human immunodeficiency virus in resource-constrained settings. We describe the methods and baseline results of a household survey that assessed the population-level impact of the national program for HIV care in Zambia and treatment in the city of Lusaka. The survey was timed with the staggered expansion of services and repeated cross-sectional surveys planned for pre-implementation and post-implementation comparisons made by community. In the initial survey round, which was performed during the early phases of the program (November-December 2004), 18,110 persons were enumerated from 3,600 households surveyed. Respondents were asked questions designed to evaluate community-level mortality and respondent knowledge and attitudes towards HIV. These findings will serve as a reliable reference in the future analysis of the population-level impact of this HIV treatment and care program in Zambia.

Trends in all-cause mortality during the scale-up of an antiretroviral therapy programme: a cross-sectional study in Lusaka, Zambia

Abstract Objective To follow the trends in all-cause mortality in Lusaka, Zambia, during the scale-up of a national programme of antiretroviral therapy (ART). Methods Between November 2004 and September 2011, we conducted 12 survey rounds as part of a cross-sectional study in Lusaka, with independent sampling in each round. In each survey, we asked the heads of 3600 households to state the number of deaths in their households in the previous 12 months and the number of orphans aged less than 16 years in their households and investigated the heads’ knowledge, attitudes and practices related to human immunodeficiency virus (HIV). Findings The number of deaths we recorded – per 100 person–years – in each survey ranged from 0.92 (95% confidence interval, CI: 0.78–1.09) in September 2011, to 1.94 (95% CI: 1.60–2.35) in March 2007. We found that mortality decreased only modestly each year (mortality rate ratio: 0.98; 95% CI: 0.95–1.00; Pu2009=u20090.093). The proportion of households with orphans under the age of 16 years decreased from 17% in 2004 to 7% in 2011. The proportions of respondents who had ever been tested for HIV, had a comprehensive knowledge of HIV, knew where to obtain free ART and reported that a non-pregnant household member was receiving ART gradually increased. Conclusion The expansion of ART services in Lusaka was not associated with a reduction in all-cause mortality. Coverage, patient adherence and retention may all have to be increased if ART is to have a robust and lasting impact at population level in Lusaka.