Selected Model Variables.

<p><b>NOTE:</b> HAART, highly-active antiretroviral therapy; DOT, directly observed therapy; QALE, quality-adjusted life expectancy.</p><p>* Complete response considered to be a sustained reduction in viral load of 2.0 log₁₀ copies/ml; partial response considered to be a sustained reduction of 0.75 log₁₀ copies/ml; non-response associated with a reduction of 0.25 log₁₀ copies/ml <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-DeHovitz1" target="_blank">[32]</a>.</p><p>† Non-elective Caesarean at term and Caesarean section with premature delivery were not associated with reduced risk of mother-to-child HIV transmission <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-The4" target="_blank">[59]</a>.</p><p>‡ Base-case probability of prematurity approximates that seen in a cohort of HIV-infected New York Medicaid recipients; upper bound based on rates of premature delivery seen in a subgroup of women receiving methadone maintenance therapy <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Turner2" target="_blank">[58]</a>.</p><p>§ In base case, risk of antiretroviral toxicity in infants was assumed to be negligible, consistent with available data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Perinatal1" target="_blank">[6]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Lipshultz1" target="_blank">[62]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-The5" target="_blank">[65]</a>. Risk of severe toxicity used in sensitivity analysis based on upper bound confidence limit for mitochondrial toxicity in a French cohort study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Blanche1" target="_blank">[63]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Barret1" target="_blank">[64]</a>. Risk of moderate toxicity based on best estimate of plausible upper bound.</p><p>∥ Base-case estimates and ranges for viral loads greater than 1000 copies/ml derived based on outcomes among individuals receiving peripartum zidovudine in a prospective multi-centre study of HIV in pregnancy <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Garcia1" target="_blank">[5]</a>.</p><p>¶ QALY and lifetime cost estimates presented in table based on the use of a 3% discount rate. Base-case quality-adjustment for HIV-uninfected individuals 45 years of age and older performed using community-derived utility estimates, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Fryback1" target="_blank">[78]</a>, while upper bound estimates are not quality-adjusted.</p><p>** Quality-adjusted survival in HIV-infected infants was estimated based on the assumption that 2/3 of person-time with HIV infection would be symptom-free, while 1/3 of person-time with HIV would include HIV-attributable symptoms. Acquired immune deficiency syndrome was assumed to be present in the last two years of life. Death due to HIV in infected children has declined markedly in both the U.S. and Europe with the advent of HAART, making estimation of survival in HIV-infected children difficult due to small numbers of events <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Sanchez1" target="_blank">[35]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Selik1" target="_blank">[37]</a>. Survival in HIV-infected children was assumed to approximate that seen in the youngest adults treated with HAART <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Egger1" target="_blank">[36]</a>. Lower bound survival estimates for HIV were generated using community-derived utility weights for life with HIV infection <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Schackman1" target="_blank">[34]</a>, while upper bound estimates were generated using more favorable survival estimates, and without quality-adjustment <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-The7" target="_blank">[79]</a>.</p><p>†† Based on in-hospital mortality in 15% of premature infants (including third-trimester still-births), with a risk of moderate to severe cognitive impairment in 10–30% <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-deKleine1" target="_blank">[68]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-International1" target="_blank">[70]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Vollmer1" target="_blank">[76]</a>. Reduction in quality-adjusted survival estimated based on health utility weight of 0.67 predicted for an individual with moderate cognitive and sensory impairment and impaired self-care ability using the Health Utilities Index Mark II <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Torrance1" target="_blank">[69]</a>.</p><p>‡‡ Based on intravenous zidovudine during 12 hour labor, and average dose of 1 ml zidovudine syrup (10 mg/ml) administered to neonate qid for 6 weeks postpartum <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Perinatal1" target="_blank">[6]</a>.</p><p>§§ Estimated based on weighted average healthcare costs associated with prematurity in infants born from 28 to 36 weeks of gestation in the state of California <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Gilbert1" target="_blank">[75]</a>, with future costs occurring due to developmental delay in 15–30% of surviving infants <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-deKleine1" target="_blank">[68]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Zupancic1" target="_blank">[74]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Vollmer1" target="_blank">[76]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Waitzman1" target="_blank">[80]</a>.</p

Sensitivity Analysis of Increasing Baseline Effectiveness of Self-Administered Antiretroviral Therapy.

<p>The proportion of women with a full response to self-administered antiretroviral therapy (i.e., 2.0 log₁₀ reduction in viral load) is presented on the X-axis. The left-sided Y-axis indicates the proportion of 200-person clinical trials that find directly observed therapy to be cost-effective for various willingness-to-pay thresholds (thick black curve, WTP = $0; medium black curve, WTP =$50,000; thin black curve, WTP = $150,000). Average incremental cost-effectiveness ratios for directly observed therapy, relative to self-administered antiretroviral therapy (dark dashed curve) are presented on the right-sided Y-axis; values below$0 indicate that directly observed therapy is a cost-saving health intervention. As the proportion of women who have a full response to self-administered HAART increases, there is a decrease in the proportion of women for whom DOT is cost-effective. An increase in the willingness-to-pay threshold leads to an increase in the proportion of women who find this intervention cost effective. Arrows indicate base-case values.</p

Selected Univariate Sensitivity Analyses of Directly Observed HAART Relative to Self-Administered HAART.

<p><b>NOTE:</b> HAART, highly-active antiretroviral therapy; QALY, quality-adjusted life years. Each estimate based on 10 simulated randomized trials with 1000 women per trial.</p><p>* Simulated through 0.75 log₁₀ reduction in viral load in 65% of women, with 0.25 log₁₀ response in the remainder.</p><p>† Highest probability of vertical transmission incorporated upper-bound transmission probability for each maternal viral load, and lower-bound estimate for effectiveness of Caesarean section, while lowest probability incorporated lower-bound transmission probabilities and upper-bound estimate for effectiveness of Caesarean section.</p><p>‡ A health care intervention is “dominated” if it costs more, but provides less health benefit, than a competing intervention. A dominated health intervention is never preferred <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Laupacis1" target="_blank">[50]</a>. A health care intervention is considered to be “cost-saving” when it costs less a competing intervention; “highly cost-effective” when it costs less than the GDP per capita; and “cost-effective” when it is between one and three times a country's GDP per capita, given that the intervention provides more health benefit than a competing intervention <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-World1" target="_blank">[49]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Laupacis1" target="_blank">[50]</a>.</p><p>§ Discounted to present value at 3% per annum.</p><p>¶ Incorporated upper- and lower-bound estimates for costs of highly-active antiretroviral therapy (HAART), peripartum zidovudine therapy, and delivery of directly observed HAART.</p><p>∥ Incorporated upper- and lower-bound estimates for costs of vaginal delivery and Caesarean section.</p

Projected Average Cost and Effectiveness of Directly Observed HAART in 5000 Simulated Randomized Trials.

<p><b>NOTE:</b> HAART, highly-active antiretroviral therapy; QALY, quality-adjusted life years.</p><p>* A health care intervention is “dominated” if it costs more, but provides less health benefit, than a competing intervention. A dominated health intervention is never preferred <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Laupacis1" target="_blank">[50]</a>. A health care intervention is considered to be “cost-saving” when it costs less, but provides more health than, a competing intervention; “highly cost-effective” when it costs less than the GDP per capita; and “cost-effective” when it is between one and three times a country's GDP per capita. A cost-saving intervention is always preferred <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-World1" target="_blank">[49]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010154#pone.0010154-Laupacis1" target="_blank">[50]</a>.</p

Simplified Depiction of Model Tree Structure.

<p>Pregnant women with HIV infection enter the third trimester of pregnancy already on highly-active antiretroviral therapy, with or without direct observation. Round “nodes” represent chance events, while squares represent clinical decisions. Women either experience preterm or term delivery, with a viral load (VL, in copies/ml) that is a function of baseline viral load, effectiveness of antiretroviral drugs, and the availability of directly observed therapy. For both detectable and undetectable viral load responses, a proportion of women receive emergency Caesarean sections. Delivery may otherwise be by elective Caesarean section, or by vaginal delivery. Vaginal delivery is an option only in women with low viral loads on antiretroviral therapy. Health outcomes in the infant are predicted by prematurity (not shown) and the occurrence of mother-to-child transmission.</p

Relationship of attendance and CHW visits^*^,^**.

*<p>CHW – community health worker.</p>**<p>The counts of the number of women attending appointments and the number of CHW visits made are both cumulative.</p>***<p>Visit policy defined as no more than ‘x’ CHW visits per woman per appointment type.</p