Quantity of resources utilized and unit costs for the provision of PMTCT services from the first antenatal visit through six months after delivery.

<p>3TC: lamivudine; ARV: antiretroviral; AZT: zidovudine; DNA: deoxyribonucleic acid; HIV: human immunodeficiency virus; NVP: nevirapine; PCR: polymerase chain reaction; PMTCT: prevention of mother-to-child transmission; USD: United States dollar.</p>a<p>A mother was considered to have initiated triple-drug ART if site registers indicated that she had either a CD4≤350 cells/µL or an ART referral indicated in the site registers.</p>b<p>Differences in means between mothers considered to have initiated triple-drug ART and not considered to have initiated triple-drug ART were calculated using an independent two-sided t-test.</p>c<p>Zambian national guidelines recommend co-trimoxazole 400 mg/80 mg tablets twice daily from 14 weeks gestation for all HIV-infected pregnant women <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>. The guidelines also recommend ARV prophylaxis for HIV-infected pregnant women not yet on triple-drug ART, including: AZT 300 mg tablets twice daily from 14 weeks gestation through one week postpartum, one NVP 200 mg tablet at delivery, and 3TC 150 mg tablets twice daily from delivery through one week postpartum <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>.</p>d<p>Zambian national guidelines recommend co-trimoxazole prophylaxis for HIV-exposed babies from six weeks of age until HIV infection is excluded, with a recommended dose of 2.5 ml of 240 mg/5 ml co-trimoxazole suspension per day for babies less than six months of age <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>. The guidelines also recommend daily NVP from birth through one week after the cessation of breastfeeding for infants born to mothers not yet on triple-drug ART and daily NVP from birth through six weeks of age for infants born to mothers on triple-drug ART, with a recommended dose of 1–1.5 ml of 10 mg/ml NVP suspension per day from birth to six weeks and 2 ml per day from six weeks to six months of age <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>. The guidelines also recommend that HIV-exposed infants receive a first HIV DNA PCR test at 6 weeks of age and a second HIV DNA PCR test at six months of age if the first HIV DNA PCR test was negative <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>.</p

Uptake, Outcomes, and Costs of Antenatal, Well-Baby, and Prevention of Mother-to-Child Transmission of HIV Services under Routine Care Conditions in Zambia

<div><p>Background</p><p>Zambia adopted Option A for prevention of mother-to-child transmission of HIV (PMTCT) in 2010 and announced a move to Option B+ in 2013. We evaluated the uptake, outcomes, and costs of antenatal, well-baby, and PMTCT services under routine care conditions in Zambia after the adoption of Option A.</p><p>Methods</p><p>We enrolled 99 HIV-infected/HIV-exposed (index) mother/baby pairs with a first antenatal visit in April-September 2011 at four study sites and 99 HIV-uninfected/HIV-unexposed (comparison) mother/baby pairs matched on site, gestational age, and calendar month at first visit. Data on patient outcomes and resources utilized from the first antenatal visit through six months postpartum were extracted from site registers. Costs in 2011 USD were estimated from the provider’s perspective.</p><p>Results</p><p>Index mothers presented for antenatal care at a mean 23.6 weeks gestation; 55% were considered to have initiated triple-drug antiretroviral therapy (ART) based on information recorded in site registers. Six months postpartum, 62% of index and 30% of comparison mother/baby pairs were retained in care; 67% of index babies retained had an unknown HIV status. Comparison and index mother/baby pairs utilized fewer resources than under fully guideline-concordant care; index babies utilized more well-baby resources than comparison babies. The average cost per comparison pair retained in care six months postpartum was $52 for antenatal and well-baby services. The average cost per index pair retained was$88 for antenatal, well-baby, and PMTCT services and increased to $185 when costs of triple-drug ART services were included.</p><p>Conclusions</p><p>HIV-infected mothers present to care late in pregnancy and many are lost to follow up by six months postpartum. HIV-exposed babies are more likely to remain in care and receive non-HIV, well-baby care than HIV-unexposed babies. Improving retention in care, guideline concordance, and moving to Option B+ will result in increased service delivery costs in the short term.</p></div

Estimated cost for hypothetical mother/baby pairs presenting to care at a gestational age of 24 weeks and receiving guideline-concordant care from the first antenatal visit through six months after delivery^a.

<p>ART: antiretroviral therapy; PMTCT: prevention of mother-to-child transmission; USD: United States dollar.</p>a<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444.s001" target="_blank">Appendix S1</a> for details on the calculation of the projected cost for mother/baby pairs receiving guideline-concordant care.</p

Average cost per mother/baby pair for actual antenatal, well-baby, and PMTCT services received and estimated triple-drug ART services received from the first antenatal visit through six months after delivery.

<p>ART: antiretroviral therapy; CI: confidence interval; PMTCT: prevention of mother-to-child transmission; USD: United States dollar.</p>a<p>A mother was considered to have initiated triple-drug ART if site registers indicated that she had either a CD4≤350 cells/µL or an ART referral indicated in the site registers.</p>b<p>Differences in means between index and comparison mother-baby pairs were calculated using an independent two-sided t-test.</p>c<p>Antenatal service costs include the costs of fixed resources and provider time per clinic visit, diagnostics, vaccines, and non-ARV drugs provided to both index and comparison mothers.</p>d<p>Well-baby service costs include the costs of fixed resources and provider time per clinic visit, vaccines, and non-ARV drugs provided to both index and comparison babies.</p>e<p>PMTCT service costs include the costs of ARV prophylaxis for index mothers not yet on triple-drug ART, ARV prophylaxis for babies, co-trimoxazole prophylaxis for index mothers and babies, and HIV DNA PCR tests for index babies.</p>f<p>Triple-drug ART service costs include the costs of pre-ART and on-ART services, including costs of fixed resources, provider time for clinic visits, ARV drugs, non-ARV drugs, and diagnostics, for index mothers considered to have initiated triple-drug ART. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444.s001" target="_blank">Appendix S1</a> for details on the estimate of triple-drug ART service costs.</p

Quantity of resources utilized and unit costs for the provision of antenatal and well-baby services from the first antenatal visit through six months after delivery.

<p>BCG: Bacille Calmette Guerin; DPT-HepB-Hib: diphtheria, pertussis, tetanus, hepatitis B, haemophilus influenza type b; HIV: human immunodeficiency virus; USD: United States dollar.</p>a<p>Differences in means were calculated using an independent two-sided t-test.</p>b<p>Mean time from the first antenatal visit to delivery for mother/baby pairs retained in care through delivery and mean time from first antenatal visit to last antenatal visit for mother/baby pairs not retained in care through delivery.</p>c<p>Zambian national guidelines recommend the following for a pregnant woman presenting to care with a gestational age of 24 weeks: four outpatient clinic visits; one hemoglobin test and one urine dipstick test at the first antenatal visit; one hemoglobin test at a subsequent antenatal visit for HIV-infected women; two rapid plasma reagin tests, one at the first visit and one three months later; one rapid HIV test at the first antenatal visit with a second, confirmatory rapid HIV test if the first rapid HIV test is positive or with repeat rapid HIV tests every three months during pregnancy and while breastfeeding if the first rapid HIV test is negative; two doses of tetanus toxoid vaccine four weeks apart for pregnant women who have not been previously vaccinated and one dose of tetanus toxoid vaccine for pregnant women who have been previously vaccinated and who have received less than five previous doses in total; daily supplements (30 tablets per month) of ferrous sulfate 200 mg tablets and folic acid 5 mg tablets; three doses (nine tablets) of sulfadoxine 500 mg/pyramethamine 25 mg for HIV-uninfected pregnant women; four tablets of mebendazole 500 mg, one at each antenatal visit; and one 2.4 MU dose of benzathine penicillin for women with a positive rapid plasma reagin test <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>.</p>d<p>Small quantities of the following resources were utilized by mothers in our sample during the postnatal period rather than the antenatal period: first rapid HIV tests (3 tests in total), ferrous sulfate 200 mg (120 tablets), folic acid 5 mg (104 tablets), and sulfadoxine 500 mg/pyramethamine 25 mg (6 tablets). This resource utilization is included in the average resource utilization figures in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone-0072444-t003" target="_blank">Table 3</a>.</p>e<p>Mean time from delivery to the last well-baby visit within six months after delivery. Patients with no visits after delivery had zero months of postnatal follow up.</p>f<p>Zambian national guidelines recommend the following care for babies during the first six months after delivery: seven outpatient clinic visits; one dose of the BCG vaccine at birth (with a repeat dose at 12 weeks of age if the infant does not have a scar); four doses of the OPV vaccine at birth, six weeks, 10 weeks, and 14 weeks; three doses of DPT-HepB-Hib at six weeks, 10 weeks, and 14 weeks; and a one-time vitamin A supplement of 100,000 IU (half of a 200,000 IU Vitamin A gel cap) at six months <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072444#pone.0072444-Government1" target="_blank">[5]</a>.</p>g<p>The cost per outpatient clinic visit of $4.01 is for the urban district hospital and includes$2.46 per visit for provider time and $1.55 per visit for fixed resources. In the primary analysis, the unit cost for the urban district hospital was applied to outpatient visits at all four study sites. The cost per outpatient clinic visit, including the cost of fixed resources and provider time, was$2.42 at the peri-urban health center, $4.45 at the rural mission health center, and$2.56 at the rural health center.</p

Baseline cohort characteristics in an evaluation of the uptake, outcomes, and costs of antenatal, well-baby, and PMTCT services under routine care conditions in Zambia.

<p>ART: antiretroviral therapy; CI: confidence interval; IQR: interquartile range; PMTCT: prevention of mother-to-child transmission.</p>a<p>Differences in means were calculated using an independent two-sided t-test. Differences in medians were calculated using the Wilcoxon rank sum test.</p

Average annual cost to produce a patient in care at six ART treatment sites in Zambia by site and time on treatment.

<p>ART: antiretroviral therapy; CI: bootstrapped confidence interval; USD: United States dollar.</p

Average annual costs at six ART treatment sites in Zambia by site and time on treatment.

<p>ART: antiretroviral therapy; CI: confidence interval; USD: United States dollar.</p

Ordinary least squares regression of the natural log of total per patient costs for the first year on ART against study site and patient-specific characteristics^a.

<p>3TC: lamivudine; ABC: abacavir; ART: antiretroviral therapy; AZT: zidovudine; CI: confidence interval; d4T: stavudine; EFV: efavirenz; FTC: emtricitabine; IDV: indinavir; LPV/r: ritonavir-boosted lopinavir; NFV: nelfinavir; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NVP: nevirapine; PI: protease inhibitor; TDF: tenofovir.</p>a<p>Analysis includes 945 patients in the subset of the sample remaining in care 12 months after ART initiation. Analysis excludes 32 patients in the subset of the sample remaining in care 12 months after ART initiation who initiated ART with a triple NRTI regimen because they had a confirmed or presumptive diagnosis of TB.</p>b<p>For interpretation, the coefficient multiplied by 100 represents the percentage change in total costs for a one unit change in the explanatory variable.</p>c<p>Reference is site 1.</p>d<p>Reference is initiation in 2006.</p>e<p>Reference is initiation on a regimen containing d4T+3TC.</p>f<p>Reference is initiation on a regimen containing NVP. The “other” category includes LPV/r, IDV, and NFV.</p

Study site and cohort characteristics in an analysis of the costs and outcomes of pediatric ART in Zambia.

<p>3TC: lamivudine; ART: antiretroviral therapy; AZT: zidovudine; d4T: stavudine; EFV: efavirenz; IQR: interquartile range; NVP: nevirapine.</p>a<p>The majority of patients initiating ART on an “other” regimen at site 3 initiated with d4T+3TC+ABC or AZT+3TC+ABC because they had a confirmed or presumptive diagnosis of TB at the time of initiation.</p