Mark J. Giganti

Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia.

Objective:To describe the association between 6-month weight gain on antiretroviral therapy (ART) and subsequent clinical outcomes. Design:A retrospective analysis of a large programmatic cohort in Lusaka, Zambia. Methods:Using Kaplan-Meier analysis and Cox proportional hazards models, we examined the association between 6-month weight gain and the risk of subsequent death and clinical treatment failure. Because it is a known effect modifier, we stratified our analysis according to body mass index (BMI). Results:Twenty-seven thousand nine hundred fifteen adults initiating ART were included in the analysis. Patients in the lower BMI categories demonstrated greater weight gain. In the post 6-month analysis, absolute weight loss was strongly associated with mortality across all BMI strata, with the highest risk observed among those with BMI <16 kg/m2 (adjusted hazard ratio 9.7; 95% CI: 4.7 to 20.0). There seemed to be an inverse relationship between weight gain and mortality among patients with BMI <16 kg/m2. Similar trends were observed with clinical treatment failure. Conclusions:Weight gain after ART initiation is associated with improved survival and decreased risk for clinical failure, especially in the lower BMI strata. Prospective trials to promote weight gain after ART initiation among malnourished patients in resource-constrained settings are warranted.

Strengthening Health Systems at Facility-Level: Feasibility of Integrating Antiretroviral Therapy into Primary Health Care Services in Lusaka, Zambia

Introduction HIV care and treatment services are primarily delivered in vertical antiretroviral (ART) clinics in sub-Saharan Africa but there have been concerns over the impact on existing primary health care services. This paper presents results from a feasibility study of a fully integrated model of HIV and non-HIV outpatient services in two urban Lusaka clinics. Methods Integration involved three key modifications: i) amalgamation of space and patient flow; ii) standardization of medical records and iii) introduction of routine provider initiated testing and counseling (PITC). Assessment of feasibility included monitoring rates of HIV case-finding and referral to care, measuring median waiting and consultation times and assessing adherence to clinical care protocols for HIV and non-HIV outpatients. Qualitative data on patient/provider perceptions was also collected. Findings Provider and patient interviews at both sites indicated broad acceptability of the model and highlighted a perceived reduction in stigma associated with integrated HIV services. Over six months in Clinic 1, PITC was provided to 2760 patients; 1485 (53%) accepted testing, 192 (13%) were HIV positive and 80 (42%) enrolled. Median OPD patient-provider contact time increased 55% (6.9 vs. 10.7 minutes; p<0.001) and decreased 1% for ART patients (27.9 vs. 27.7 minutes; p = 0.94). Median waiting times increased by 36 (p<0.001) and 23 minutes (p<0.001) for ART and OPD patients respectively. In Clinic 2, PITC was offered to 1510 patients, with 882 (58%) accepting testing, 208 (24%) HIV positive and 121 (58%) enrolled. Median OPD patient-provider contact time increased 110% (6.1 vs. 12.8 minutes; p<0.001) and decreased for ART patients by 23% (23 vs. 17.7 minutes; p<0.001). Median waiting times increased by 47 (p<0.001) and 34 minutes (p<0.001) for ART and OPD patients, respectively. Conclusions Integrating vertical ART and OPD services is feasible in the low-resource and high HIV-prevalence setting of Lusaka, Zambia. Integration enabled shared use of space and staffing that resulted in increased HIV case finding, a reduction in stigma associated with vertical ART services but resulted in an overall increase in patient waiting times. Further research is urgently required to assess long-term clinical outcomes and cost effectiveness in order to evaluate scalability and generalizability.

Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.

Background:In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. Methods:We compared drug substitutions, mortality, and “programmatic failure” among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. Results:Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. Conclusions:TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambias policy decision.

Optimal time on HAART for prevention of mother-to-child transmission of HIV

Objectives: To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery—duration of antenatal HAART—on perinatal HIV infection. Design: We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction test between 3 and 12 weeks of life. Methods: We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection. Results: From January 2007 to March 2010, 1813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (SD ± 6), median CD4+ cell count was 231 cells per microliter (interquartile range: 164-329), and median duration of antenatal HAART was 13 weeks (interquartile range 8-19). Fifty-nine (3.3%) infants were HIV infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared with women initiating HAART at least 13 weeks before delivery, women on HAART for ≤4 weeks had a 5.5-fold increased odds of HIV transmission (95% confidence interval: 2.6 to 11.7). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART. Conclusions: Low rates of mother-to-child HIV transmission can be achieved within programatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission programs is achieved by initiating HAART at least 13 weeks before delivery.

Taking ART to scale: determinants of the cost and cost-effectiveness of antiretroviral therapy in 45 clinical sites in Zambia.

Background We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). Methods We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. Results The program cost

Implementation of the Zambia Electronic Perinatal Record System for comprehensive prenatal and delivery care

69.7 million for 125,436 person-years of ART, or

Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia

556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was

Hormonal contraception and HIV disease progression: a multicountry cohort analysis of the MTCT-Plus Initiative

833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector. Conclusions and Significance The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.

Determinants of stillbirth in Zambia.

To characterize prenatal and delivery care in an urban African setting.

CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia.

Objective:To evaluate the relationship between early CD4+ lymphocyte recovery on antiretroviral therapy (ART) and subsequent survival among low body mass index (BMI) HIV-1-infected adults. Design:Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. Methods:We evaluated ART-treated adults enrolled in care for more than 6 months. We stratified this study population according to World Health Organization (WHO) malnutrition criteria: normal (BMI ≥18.5 kg/m2), mild (17.00–18.49), moderate (16.00–16.99), and severe (<16.0). We used Cox proportional hazards regression to estimate the subsequent risk of death associated with absolute CD4+ cell count change over the first 6 months on ART. To account for effect modification associated with baseline CD4+ cell count, a weighted summary measure was calculated. Results:From May 2004 to February 2009, 56 612 patients initiated ART at Lusaka district clinics; of these, 33 097 (58%) were included in this analysis. The median change in 0–6 month CD4+ cell count in each baseline BMI strata varied from 127 to 131 cells/μl. There was a statistically significant, inverse association between baseline BMI and the post 6-month hazard for mortality only among those patients with less than 100 cells/μl increase in the first 6 months of ART. A CD4+ cell count increase of at least 100 cells/μl over the first 6 months of ART was not associated with a higher hazard for mortality, regardless of baseline BMI. Conclusions:Low baseline BMI and attenuated CD4+ cell count response at 6 months had a compounding, negative impact on post 6-month survival. Specific guidelines for monitoring ART response using immunologic criteria may be warranted for low BMI patients.