Drug Resource Enhancement Research Articles

Who will be lost? Identifying patients at risk of loss to follow-up in Malawi. The DREAM Program Experience.

Retention of subjects in HIV treatment programmes is crucial for the success of treatment. We evaluated retention/loss to follow-up (LTFU) in subjects receiving established care in Malawi. Data for HIV-positive patients registered in Drug Resource Enhancement Against AIDS and Malnutrition centres in Malawi prior to 2014 were reviewed. Visits entailing HIV testing/counselling, laboratory evaluations, nutritional evaluation/supplementation, community support, peer education, and antiretroviral (ART) monitoring/pharmacy were noted. LTFU was defined as > 90 days without an encounter. Parameters potentially associated with LTFU were explored, with univariate/multivariate logistic regression analyses being performed. Fifteen thousand and ninety-nine patients registered before 2014; 202 (1.3%) were lost to follow-up (LTFU) (1.3%). Nine (0.5%) of 1744 paediatric patients were LTFU vs. 1.4% (n = 193) of 13 355 adults (P < 0.001). Subjects who were LTFU had fewer days in care than retained subjects (1338 vs. 1544, respectively; P < 0.001) and a longer duration of ART (1530 vs. 1300 days, respectively; P < 0.001). Subjects who were LTFU had higher baseline HIV viral loads (P = 0.016) and higher body mass indexes (P < 0.001), were more likely to live in urban settings (88% of patients who were LTFU lived in urban settings) with better housing [relative risk (RR) 2.3; 95% confidence interval (CI) 1.67-3.09; P < 0.001], and were more likely to be educated (RR 1.88; 95% CI 1.42-2.50; P < 0.001). Distance to the centre and cost of transportation were associated with LTFU (RR 3.4; 95% CI 2.84-5.37; P < 0.001), as was absence of a maternal figure (RR 1.57; 95% CI 1.17-2.09; P < 0.001). Viral load, distance index, education and a maternal figure were predictive of LTFU. Educated, urbanized HIV-infected adults living far from programme centres are at high risk of LTFU, particularly if there is no maternal figure in the household. These variables must be taken into consideration when developing retention strategies.

An assessment of option B implementation for the prevention of mother to child transmission in Dschang, Cameroon: results from the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) cohort

IntroductionScaling up of antiretroviral therapy (ART) to HIV+ pregnant women is crucial for the elimination of HIV infection in children. The aim of this study was to evaluate the feasibility and effectiveness of triple ART for Prevention of Mother-to Child Transmission (PMTCT) in Cameroon.MethodsHIV-positive pregnant women attending the DREAM Centre of Dschang, Cameroon for prenatal care were enrolled in a prospective cohort study, and received ART until the end of breastfeeding or indefinitely if their CD4 count was <350mm3. Infants were evaluated for HIV infection at 1, 6 and 12 months of age.ResultsA total of 298 women were enrolled. Among them, 152 were already on established ART. Women were followed until 6 months after delivery with a retention rate of 92.6%. Eight women died. Those with a CD4 count <350 cells/mm3 during pregnancy had the highest mortality risk (RR 2.53; 95% CL= 1.86-3.44). The HIV transmission rate was 1.2% at 12 months with an HIV free survival of 91%. In the proportional Cox regression analysis, the following factors were positively associated with infant mortality: maternal CD4< 350 cells/mm3, no breastfeeding in the first 6 months of life, weight-for-age z score<-2.ConclusionResults confirm the feasibility and effectiveness of the implementation of Option B, with very low rates of HIV MTC transmission, and potential benefits to the health of mothers and infants with earlier initiation of ART. Breastfeeding again demonstrates to be highly beneficial for the growth and survival of HIV exposed children.

Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model.

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%–88% while retention rates at 18–24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.

Predictors of Adverse Outcomes in HIV-1–infected Children Receiving Combination Antiretroviral Treatment

HIV-infected children have less access to combination antiretroviral therapy as compared with adults in resource-limited settings. Growth faltering, loss to follow-up (LTFU) and high mortality are frequently seen. A retrospective cohort study was performed with parameters extracted from the Drug Resource Enhancement against AIDS and Malnutrition database for HIV-infected, antiretroviral naïve children under 15 years presenting for care at 17 Drug Resource Enhancement against AIDS and Malnutrition centers in Mozambique, Malawi and Guinea between January 2005 to December 2008. Predictors of time-to-death, time-to-LTFU and persistence of malnutrition by Cox's regression and Kaplan-Meier were determined. 2215 children presented to care with 1343 (61%) being ≤ 5 years. At baseline, stunting and malnutrition occurred in 40% and 25%, respectively; 75% of 2149 children had CD4 cell percentages less than 20; median HIV RNA, log10 cp/mL, was 4.97 in 1927 patients. Over time 238 children died (10.7%; 2.7% person-years [PY]) 63 were LTFU (2.8%; 0.7% PY). By multivariate analysis, mortality was associated with virus load (hazards ratio: 1.19; confidence interval: 1.01-1.402, P = 0.038) and reduced weight-for-age Z scores (hazards ratio: 0.590; confidence interval: 0.53-0.66, P < 0.001). LTFU was associated with low weight-for-height Z scores (hazards ratio: 0.71; confidence interval: 0.51-0.97, P = 0.031). At 12 months after combination antiretroviral therapy, anthropometric parameters significantly improved in 1226 children (P < 0.001); virus load declined to <400 copies/mL in over 60%. Despite advanced HIV disease, children initiating combination antiretroviral therapy had mortality rates of 2.7% p/PY with overall attrition rates of 11.7% p/100 PY, with significant reversal of negative anthropometric markers, and improvement of immunological and virological parameters in children with 12 months of follow-up.

Reduction of Maternal Mortality with Highly Active Antiretroviral Therapy in a Large Cohort of HIV-Infected Pregnant Women in Malawi and Mozambique

BackgroundHIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002.MethodsRecords for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2).Results10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23–30), CD4 count 392 cells/mm3 (IQR:258–563), Viral Load log10 3.9 (IQR:3.2–4.4), BMI 23.4 (IQR:21.5–25.7), Hemoglobin 10.0 (IQR: 9.0–11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with <than 350 CD4 cells/mm3 and 0.7% in women with greater than 350 CD4s cells/mm3 [OR = 1.9 (CL 1.3–2.9) p = 0.001]. Mortality was higher in patients with shorter antenatal HAART: 22/991 (2.2%) if less than 30 days and 79/9159 (0.9%) if 31 days or greater [OR = 2.6 (CL 1.6–4.2) p<0.001]. By multivariate analysis, shorter antenatal HAART (p<0.001), baseline values for CD4 cell count (p = 0.012), hemoglobin (p = 0.02), and BMI (p<0.001) were associated with mortality. Four years later, survival was 92% for women with shorter antenatal HAART and 98% for women on established therapy prior to pregnancy, p = 0.001.ConclusionsAntiretrovirals for PMTCT purposes have significant impact on maternal mortality as do CD4 counts and nutritional status. In resource-limited settings, PMTCT programs should provide universal HAART to all HIV+ pregnant women given its impact in prevention of maternal death.

Predicting Trends in HIV-1 Sexual Transmission in Sub-Saharan Africa Through the Drug Resource Enhancement Against AIDS and Malnutrition Model: Antiretrovirals for 5 Reduction of Population Infectivity, Incidence and Prevalence at the District Level

The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa. Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV. Data from 26565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years. Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa.

Extended antenatal use of triple antiretroviral therapy for prevention of mother-to-child transmission of HIV-1 correlates with favorable pregnancy outcomes

To evaluate pregnancy outcomes in a cohort of HIV-infected women receiving triple antiretroviral therapy (ART) for prevention of mother-to-child-transmission. A retrospective cohort study with review of records of 3273 HIV-positive women receiving prenatal care in Malawi and Mozambique from July 2005 to December 2009 was conducted in Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) centers. Patients were offered nevirapine-based triple ART initiated in pregnancy until 6 months postpartum. Main outcome measures were maternal mortality, abortion/stillbirth, prematurity, and low birth weight. Maternal mortality was 1.2% (42/3273): 7.4% in 68 women with no antenatal ART and 0.7% in 1370 with at least 90 days of antenatal ART [P < 0.001; odds ratio (OR) 0.29 (95% confidence interval [CI] 0.14-0.96]. Abortion/stillbirth was 5.2% (169/3273): 26.5% in 68 women with no ART and 5.0% in 1370 women with at least 90 days of antenatal ART [P < 0.001; OR 0.39 (95% CI 0.27-0.57)]. Prematurity was 19.1%: 70% in 10 women with no antenatal ART and 8.5% in 1330 women with at least 90 days of antenatal ART [P < 0.001; OR 0.15 (95% CI 0.14-0.19)]. Low birth weight was 11.5% (57/496) and not associated with ART duration. The protective effect of antenatal ART against mortality, fetal demise, and prematurity was independent of CD4 strata. Multivariate analysis for BMI, CD4 cell count, virus load, days in care, predelivery length of ART, and hemoglobin demonstrated an independent association between predelivery length of ART and CD4 with maternal mortality, abortion/stillbirth, and prematurity. ART toxicities were infrequent (5.2%). Antenatal triple ART reduces adverse pregnancy outcomes in HIV-infected women.

Cost-Effectiveness of Using HAART in Prevention of Mother-To-Child Transmission in the DREAM-Project Malawi

Cost-effectiveness analysis are crucial in the management of the HIV/AIDS epidemic, particularly in resource-limited settings. Such analyses have not been performed in the use of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission (PMTCT). Cost-effectiveness analysis of HAART approach in Malawi for PMTCT. In 2 health centres in Malawi 6500 pregnant women were tested; 1118 pregnant women completed the entire Drug Resource Enhancement against Aids and Malnutrition-Project Malawi (DREAM - PM) PMTCT protocol. The costs of the intervention were calculated using the ingredients method. Outcomes estimated were cost for infection averted and cost for DALY saved compared with no intervention. From a private perspective cost for HIV infection averted was US $998 and cost per DALY saved was US $35.36. From a public perspective, the result became negative as follows: -261 and -16.55, respectively (lower cost than the cost of the therapy for an HIV+ child). The univariate sensitivity analysis showed that the cost for DALY saved always remained under the threshold of US $50, largely under the threshold given by the per capita yearly income in Malawi (US $667 PPD). Administration of HAART in a PMTCT programme in resource-limited settings is cost-effective. Drugs and laboratory tests are the most significant costs, but further reduction of these expenses is possible.

Extended antenatal antiretroviral use correlates with improved infant outcomes throughout the first year of life

To evaluate the effect of extended antenatal triple antiretroviral therapy (ART) on infant outcomes. Retrospective cohort study using pooled data from health clinics in Malawi and Mozambique from July 2005 to December 2009. Computerized records of 3273 HIV-infected pregnant women accessing Drug Resource Enhancement Against AIDS and Malnutrition centers were reviewed. ART regimens consisted of nevirapine-based HAART as of 14-25 weeks gestation until 6 months postpartum. Infant infection was determined at 1, 6 and 12 months of age by branched DNA. A total of 3071 pregnancies resulted in 3148 live births. Lost to follow-up, infant deaths and HIV-1 infection rates at 1 and 12 months were 1.3 and 11.5, 0.8 and 6.7 and 0.8 and 2.0, respectively. Infant HIV-1-free survival at 12 months was 92.5%. Mother-to-child transmission and/or infant deaths correlated with length of maternal antenatal ART by multivariate analysis at 1, 6 and 12 months: 14% in women with more than 30 days of triple antenatal ART and 6.9% in mothers receiving at least 90 days of antenatal ART, P = 0.001. Fifty percent of 54 episodes of transmission occurred in women with higher CD4 cell counts (>350 cells/μl). Infant mortality was 67/1000, lower than background rates (78-100/1000). Growth failure (weight-for-age Z score <-2) was present in 8% of infants around birth, 6% at 6 months, 23% at 12 months (lower than country-specific rates). Extended antenatal ART is protective against adverse infant outcomes up to 12 months of age even in children born to mothers with higher CD4 cell counts.

HAART during pregnancy and during breastfeeding among HIV-infected women in the developing world: has the time come?

This editorial comment focuses upon the idea of offering HAART to all HIV-infected pregnant women including those in developing countries and considers the barriers or problems associated with this concept as well as the positive outcomes. It states that more data is needed but that a strategy would be to ensure that women with CD4 cell count below 350 cells/ml in resource-limited settings receive HAART that would then be continued after breastfeeding cessation for maternal health.

Increased Infant Human Immunodeficiency Virus-Type One Free Survival at One Year of Age in Sub-Saharan Africa With Maternal Use of Highly Active Antiretroviral Therapy During Breast-Feeding

Reduction of HIV-1 breast-feeding transmission remains a challenge for prevention of pediatric infections in Sub-Saharan Africa. Provision of formula decreases transmission but often increases child mortality in this setting. A prospective observational cohort study of HIV-1 exposed infants of mothers receiving pre and postnatal medical care at Drug Resource Enhancement Against AIDS and Malnutrition centers in Mozambique was conducted. Live-born infants of HIV-1-infected women receiving medical care were enrolled. HIV-1 testing was performed at 1, 6, and 12 months of age using branched DNA. Mothers were counseled to breast-feed exclusively for 6 months and were provided HAART antenatally and postnatally for the first 6 months. Women with CD4 cell counts less than 350/cmm at baseline continued HAART indefinitely. Of 341 infants followed from birth, 313 mother-infant pairs (92%) completed 6 months and 283 (83%) completed 12 months of follow-up. HIV-1 diagnosis was ascertained in 287 infants (84%) including 4 who died. There were 8 cases of HIV-1 transmission: 4 of 341 (1.2%) at 1 month, 2 of 313 (0.6%) at 6 months, and 2 of 276 (0.7%) at 12 months (cumulative rate: 2.8%). Two mothers (0.6%) and 11 infants (3.2%) died. Maternal and infant mortality rates were 587 of 100,000 and 33 of 1000, while country rates are 1000 of 100,000 and 101 of 1000. HIV risk reduction was 93% and HIV-free survival at 12 months was 94%. Late postnatal transmission of HIV-1 is significantly decreased by maternal use of HAART with high infant survival rates up to 12 months of age.

The DREAM model's effectiveness in health promotion of AIDS patients in Africa

This study evaluates the effectiveness of a holistic model for treating people living with AIDS in Africa; the model aims to improve knowledge about AIDS prevention and care, increase trust in the health centre, impact behaviour, and promote a high level of adherence to HAART. The study took place in the context of the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) programme in Mozambique, designed by the Community of Sant'Egidio to treat HIV patients in Africa. It provides patients with free anti-retroviral drugs, laboratory tests (including viral load), home care and nutritional support. This is a prospective study involving 531 patients over a 12-month period. The patients, predominantly poor and with a low level of education, demonstrated a good level of knowledge about AIDS (more than 90% know how it is transmitted) and trust in the treatment, with a relatively small percentage turning to traditional healers. Overall the patients had a low level of engaging in risky sexual behaviour and a very good level of adherence to HAART (69.5% of the 531 subjects had a pill count higher than 95%). The positive results of the programme's educational initiatives were confirmed with the patients' good clinical results.

Treatment acceleration program and the experience of the DREAM program in prevention of mother-to-child transmission of HIV

The Drug Resource Enhancement against AIDS and Malnutrition (DREAM) program is a large antiretroviral therapy treatment program financed by the Treatment Acceleration Program (TAP) of the World Bank. In addition to provision of antiretroviral treatment to individuals infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, one major aspect of the DREAM program is nutritional supplementation and prevention of mother-to-child transmission (PMTCT) of HIV. HIV-positive pregnant women enrolled in the DREAM program receive highly active antiretroviral therapy (HAART) free of charge from the 25th week of gestation, irrespective of clinical stage, CD4 count, and viral load. Their infants receive post-exposure prophylaxis. From 2004 to 2006, women enrolled in the DREAM program in Mozambique, Tanzania, and Malawi received water filters and formula for the first 6 months of lactation. In a second cohort starting in 2005 until 2006 in Mozambique, women received HAART for up to 6 months after delivery and were given the option to breastfeed. We conducted a comparative analysis of the two cohorts of HIV-positive pregnant women followed prospectively and evaluated HIV-1 mother-to-child transmission rates, infant morbidity, and mortality in both cohorts. In the first cohort, 879 live-born children were delivered, with 809 evaluable infants at 1 and 6 months. In the second cohort, 341 infants were delivered and evaluable at 1 month, and 251 infants were evaluable at 6 months. At age 1 month, HIV-1 transmission rates were 4/341 (1.2%) among breastfed infants and 7/809 (0.8%) among formula-fed infants. At age 6 months, HIV-1 mother-to-child transmission rates were 2/251 (0.8%) among breastfed infants of women receiving HAART and 15/809 (1.8%) among formula-fed infants (chi = 0.77, P = 0.38 [NS]). The cumulative incidence rate at 6 months of age was 2.7% for formula-fed infants and 2.2% for breastfed infants (chi = 0.27, P = 0.60 [NS]). There was a trend for HIV-1 infection rates to be slightly greater among formula-fed infants, but overall mother-to-child transmission rates in both cohorts were extremely low. Most infants did relatively well on both feeding regimens. Observed Z scores were greater than among the general infant population in the community. Z scores < or =2.0 for weight by age occurred in 92/809 formula-fed infants (11.4%) and in 28/251 breastfed infants (11.1%). The rates of anemia in the study infant population were also lower than that of the general population. A hemoglobin value <8 g/dl was found in 40/809 formula-fed infants (4.9%) and in 17/251 breastfed infants (6.8%) (chi = 0.92, P = 0.33). The mortality rate at 6 months of age was 27 per 1000 person-years among formula-fed infants and 28.5 per 1000 person-years in breastfed infants--both considerably lower than the rates of 101 per 1000 person-years observed in Mozambique. The DREAM HIV-1 PMTCT protocol was safe and efficacious in reducing transmission in infants of 1 and 6 months of age. Results were comparable to those from developed countries. Breastfeeding among HIV-1 infected mothers receiving HAART posed no additional risk of late postnatal HIV-1 transmission to the infant by 6 months of age.

Antiretroviral Therapy Among HIV-Infected Breastfeeding Mothers: A Promising Strategy to Prevent HIV Postnatal Transmission in Africa

Evaluation of: Giuliano M, Guidotti G, Andreotti M et al.: Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load: a study within the Drug Resource Enhancement Against AIDS and Malnutrition Program. J. Acquir. Immune Defic. Syndr. 44(3), 286–291 (2007). Maternal highly active antiretroviral therapy (HAART) starting during the late prenatal period and prolonged during lactation is a potentially interesting strategy to prevent mother-to-child transmission of HIV through breastfeeding in Africa. In this report, Giuliano and colleagues demonstrated that HIV-infected women treated with HAART from before delivery had lower cell-free HIV RNA load in breast milk and were less likely to have a detectable viral load in this compartment 1 week after delivery, when compared with untreated women. Antiretroviral therapy among HIV-infected breastfeeding mothers could thus be a promising strategy to prevent HIV transmission through breast milk in Africa if further larger studies confirm its safety. This strategy could also provide a link between prevention and care, since maternal HAART provided in pregnancy and during the breastfeeding period can be thereafter continued among women who meet the criteria for their own health.

Improving adherence to highly active anti-retroviral therapy in Africa: the DREAM programme in Mozambique

Ensuring high levels of adherence to highly active anti-retroviral therapy (HAART) is a priority in treating people living with AIDS. This study reports the rates of adherence of patients served by DREAM (Drug Resource Enhancement against AIDS and Malnutrition) in the city of Matola, Mozambique. DREAM, an innovative programme tailored for Africa, was implemented by the Community of Sant'Egidio in August 2001. DREAM provides patients with anti-retroviral drugs and laboratory tests at no charge, and is based on a particular strategy of health education and organization of services designed for a population that is predominantly poor and has a low level of formal education. This study analyzes the adherence of 154 patients over a period of 6 months. In evaluating adherence, two indicators were used: (1) the percentage of appointments kept for check-ups, tests and the collection of medicine, and (2) the overall change in the patients' blood chemistry over the 6-month period. Of the 154 patients, 127 (82.5%) kept more than 90% of their appointments. Adherence to the programme was further confirmed by a relevant increase of hemoglobin levels and CD4 counts, and a significant decrease in the viral loads among the 154 patients.

Is total lymphocyte count a reliable predictor of the CD4 lymphocyte cell count in resource-limited settings?

Although the depletion of CD4 T cells remains the most reliable marker for estimating the degree of immunosuppression in HIV-1-infected individuals, several authors have investigated the possible prognostic and predictive role offered by total lymphocyte count (TLC) as a surrogate of the CD4 cell count in resource-limited settings (RLS). TLC offers the advantages of being less expensive and less complicated than the CD4 cell count. In addition, the equipment needed is already available in most RLS. Despite these potential advantages, papers recently published on this issue do not demonstrate that TLC fulfils the rigorous requirements as to sensitivity and specificity, particularly needed when methods already proved to be accurate detectors of immunosuppression (such as CD4 cell count) are available [1–6]. The rapid tests for diagnosing HIV infection in adolescents and adults are an example of this, having replaced enzyme-linked immunosorbent assay and Western blot in RLS, not only because of their lower cost, but also because of their good mean sensitivity and specificity (98.5 and 93.4%, respectively). The aim of this study was to assess the impact of considering TLC alone on the introduction of antiretroviral therapy in an asymptomatic HIV-infected African population undergoing regular CD4 lymphocyte controls in the framework of a highly active antiretroviral therapy protocol. Moreover, the effectiveness of TLC as a marker of immunosuppression was compared with that of another marker, the body mass index (BMI), requiring the simple measurement of the anthropometrical parameters of weight and height. The study was carried out from March 2002 to May 2003 by analysing 651 paired TLC and CD4 lymphocyte counts collected from asymptomatic patients (1–2 World Health Organization clinical staging) followed in a day hospital for individuals with HIV infection managed by the Community of Sant'Egidio in cooperation with the Ministry of Health of Mozambique. The day hospital, located in Matola-Maputo, Mozambique, is part of the DREAM programme (Drug Resource Enhancement against AIDS and Malnutrition) [7]. TLC was measured by an Act-5 Diff Beckman automated blood-analyser; lymphocyte-phenotyping was performed by ‘lyse-non-wash’ flow-cytometry (EPICS-MCL XL, Beckman Coulter, Johannesburg, South Africa). In 468 cases, BMI was also available, calculated on the same day the patients’ blood was collected. The mean value of TLC was 1935 cells/mm3 (range 200–13 800; SD ± 1035); average BMI was 22.04 (range 11.02–40.06; SD ± 4.17). CD4 lymphocytes were less than 200 cells/mm3 in 277 cases (42.4%). The two-tail Pearson correlation between the CD4 cell count and the other two variables gave a value of r = 0.341 and r = 0.314 for BMI and TLC, respectively (P < 0.001 in both cases) (Table 1).Table 1: CD4 cell count, total lymphocyte count and body mass index: values and statistical correlations.A further analysis was performed by binary logistic regression, to resolve the heterogeneity between dependent and independent variables (although dichotomization of the variables is always required). CD4 cell counts (dependent variable) were divided into two groups, above or below 200 cells/mm3 (the threshold under which patients should receive antiretroviral treatment). The threshold value for the dichotomization of TLC was 1200 cells/mm3, considered a marker of serious immunosuppression according to World Health Organization guidelines for RLS. For BMI, 18 was chosen as the threshold value that indicates malnutrition. The two independent variables were separately compared with dependent variables in order to evaluate their predictive effectiveness. The classification capability of the two models was 65.2% for BMI and 67.6% for TLC; sensitivity was 47 and 48.9%, respectively, whereas specificity was 78.5% for BMI and 81.3% for TLC (Table 1). Consequently, using TLC as a marker for introducing therapy would have resulted in initiating antiretroviral treatment for approximately 20% of patients who could wait according to international guidelines. At the same time, TLC would have excluded from treatment approximately 50% of those having an indication for starting therapy. Interestingly, using BMI instead of TLC would have led to similar results. In confirmation of the results of binary logistic regression, the use of receiving operating characteristics curves for the two variables considered demonstrated that neither TLC nor BMI had the ability to provide accurate discrimination (29% for TLC and 32% for BMI). In conclusion, the use of TLC as a surrogate for the CD4 cell count appears to be unjustified, as it does not fulfil the minimal requirements of validity, whereas it appears to provide a level of information comparable with a simple evaluation of the anthropometric status (such as BMI), which is also indicative of the patients’ clinical condition. The low sensitivity of TLC delays therapeutic decisions, and may lead to disease progression and death in some immunosuppressed patients who could have taken advantage of therapy. Moreover, starting treatment in a significant percentage of patients, in the absence of serious immunosuppression, would overcome the economic advantage obtained by substituting TLC for CD4 cell count.