Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (NCT00993031), a randomized phase 3 study. The primary outcome is Prevalence of Malaria Defined as Positive Placental Blood Smear.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group, open-label trial conducted at a single site. It is listed as phase 3 and completed, with 389 participants enrolled. The comparison was between protease inhibitor-based antiretroviral therapy and non-protease inhibitor-based therapy among HIV-infected pregnant women at high risk of malaria.

The arm descriptions identify zidovudine and lamivudine in both regimens. Group A included lopinavir/ritonavir, while Group B included efavirenz. The listed interventions also include zidovudine, lamivudine, lopinavir/ritonavir, and efavirenz. Masking is listed as none, so the trial was open-label. The registry record does not report further details about how randomization was generated or concealed.

The primary endpoint was the number of participants with a positive placental blood smear for malaria at delivery. The reported primary analysis included 158 participants in each treatment group. The broader study summary says the trial also enrolled infants at delivery. It lists additional maternal and placental outcomes, including placental malaria assessed by rapid diagnostic testing and histopathology, malaria treatments, a composite clinical outcome, severe maternal anemia, pre-eclampsia, and maternal HIV RNA suppression.

The record lists the study sponsor as the University of California, San Francisco. It does not report the original sample-size justification, the planned statistical analysis protocol, interim analyses, or details about allocation concealment. The enrollment total and the endpoint-specific analysis counts describe different aspects of the trial; the registry record does not explain why the primary endpoint counts are smaller than overall enrollment.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Placental blood smear

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Prevalence of Malaria Defined as Positive Placental Blood Smear, measured over Delivery.

The primary endpoint counts participants whose placental blood smear was positive for malaria at delivery. It is a binary outcome at the participant level: each participant either had a positive smear or did not. The registry describes the measure as the number of participants with a positive placental blood smear, rather than a measure of parasite quantity or severity.

Placental malaria was the central outcome because the study was designed to compare whether the two antiretroviral regimens were associated with different risk of malaria affecting the placenta during pregnancy. A placental blood smear at delivery provides a direct laboratory classification for this endpoint at the specified assessment time. The endpoint is distinct from other registry outcomes that assess placental malaria by rapid diagnostic testing or histopathologic analysis; those are separate measures and need not classify every participant identically.

The posted primary counts are 5 positive smears among 158 participants with protease inhibitor therapy and 6 among 158 without protease inhibitor therapy. These counts describe the analyzed groups, not necessarily everyone enrolled. The registry record does not report whether all randomized participants had a placental smear available or how missing endpoint assessments were handled.

7. Results Posted in the Registry

• Without Protease Inhibitor: 3.8% (6/158) versus 3.2% (5/158) on control; risk difference 0.6 percentage points (95% CI -3.4 to 4.7), risk ratio 1.20 (0.37–3.85); unadjusted two-proportion z-test p = 0.759.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Placental Malaria Defined as Positive Placental RDT

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Without Protease Inhibitor: 4.5% (7/155) versus 3.8% (6/157) on control; risk difference 0.7 percentage points (95% CI -3.7 to 5.1), risk ratio 1.18 (0.41–3.44); unadjusted two-proportion z-test p = 0.759.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Without Protease Inhibitor and the control. The interval gives the range of effects that remain compatible with the data.

Placental Malaria Defined Placental Histopathologic Analysis

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Without Protease Inhibitor: 28.5% (47/165) versus 38.3% (62/162) on control; risk difference -9.8 percentage points (95% CI -20.0 to 0.4), risk ratio 0.74 (0.55–1.02); unadjusted two-proportion z-test p = 0.061.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Without Protease Inhibitor and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • With Protease Inhibitor: 5.7% (11/194) versus 5.6% (11/195) on control; risk difference 0.0 percentage points (95% CI -4.6 to 4.6), risk ratio 1.01 (0.45–2.26); unadjusted two-proportion z-test p = 0.990.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between With Protease Inhibitor and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover multiple definitions of placental malaria, maternal malaria during and after pregnancy, maternal and pregnancy outcomes, and maternal HIV RNA suppression. The posted secondary results do not form a single uniform pattern: different outcome definitions and assessments show different estimates and degrees of uncertainty. These measures address related but distinct questions, so they should be interpreted according to their own endpoint definitions rather than treated as interchangeable versions of the primary result.

The secondary placental assessments can add context to the primary blood-smear endpoint, but they do not replace it. A rapid diagnostic test, a blood smear, and histopathologic analysis are different ways of classifying placental malaria. Divergence among their observed results can reflect differences in measurement and analyzed participants; the registry record does not provide enough information to explain the specific pattern. Other secondary outcomes broaden the clinical description but are not the primary test of the stated study hypothesis.

Many secondary questions increase the chance that at least one result will appear notable by chance when each is assessed separately. The posted secondary p-values are unadjusted where recalculations are listed, and the registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting these outcomes. Accordingly, an isolated secondary result should carry less weight than a clearly specified primary comparison and should be viewed as exploratory unless the full analysis plan establishes otherwise. The registry record does not report that plan.

Overall, the secondary findings provide additional outcome-specific information, not a definitive resolution of the primary comparison. Their value is in showing what was measured and where further interpretation may be warranted, while accounting for multiplicity, differing endpoint definitions, and uncertainty.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Placental Malaria Defined as Positive Placental RDT
• Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy
• Prevalence of Composite Clinical Outcome Defined by LBW, Stillbirth(Intrauterine Fetal Demise >20wks GA), Late Spontaneous Abortion(Miscarriage 12-20wks GA), Preterm Delivery(<37wks Gestation), Neonatal Death(Death of Liveborn Infant Within First 28days)
• Placental Malaria Defined Placental Histopathologic Analysis
• Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy
• Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group
• Incidence of Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick
• Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL

9. Statistical Interpretation

10. Statistical Methods Explained

For the primary endpoint, the outcome is binary: a placental blood smear was either positive or not positive. A natural summary is the proportion of participants with a positive result in each group. A risk difference subtracts one group's proportion from the other group's proportion. Its zero value represents equal observed proportions; a positive or negative value indicates the direction of the observed difference according to the stated subtraction order. The recalculated risk difference is 0.006, comparing participants without a protease inhibitor against those with one.

What does the risk ratio describe?

A risk ratio compares the event proportion in one group with the event proportion in another. A value of one corresponds to equal proportions. Values on either side of one represent different relative risks, with the interpretation depending on which group is in the numerator. The registry reports a risk ratio of 0.83 for the primary outcome. Its confidence interval, .26 to 2.67, is wide and includes one. The registry record identifies a chi-squared method for this reported analysis.

How should a confidence interval be read?

A confidence interval communicates uncertainty around an estimated effect. It is not a guarantee that the true effect lies within the particular interval, and its width depends on the data and method used. For a risk difference, an interval spanning zero is compatible with no difference as well as effects in either direction. For a risk ratio, the corresponding reference value is one. The primary intervals span their respective reference values, so the posted estimates are not precise enough to distinguish a small difference from effects in either direction.

What does the p-value add?

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The sponsor-reported primary p-value is .76, and the unadjusted recalculation gives p = 0.759. These values are close, and both are consistent with the same broad reading: the observed data do not provide strong evidence against equal group risks. They do not prove equality.

Why are there both reported and recalculated estimates?

The registry lists the sponsor's analysis as a chi-squared test of a risk ratio. A simple unadjusted recalculation can also be made from the posted counts and denominators. That recalculation uses summary data only; it cannot reproduce analyses that might use participant-level information, adjustments, or details not recorded in the registry. For this primary result, the reported and recalculated p-values are close. The recalculated risk difference offers an absolute-scale description alongside the registry's relative-scale risk ratio. These are different ways to express the comparison, not independent replications of the trial.

What do sparse counts imply?

The primary endpoint has few positive events in each group. With sparse binary outcomes, estimates can be unstable and confidence intervals can be broad, because a small change in the event count can materially affect the estimated proportion or relative contrast. The uncertainty in this result is visible in the wide intervals. A chi-squared analysis is the method recorded by the registry; details of any checks of its assumptions or alternative analyses are not reported in the registry record.

More generally, the risk difference is useful for expressing an absolute contrast, while the risk ratio describes a relative contrast. Neither scale is universally sufficient on its own. A full interpretation considers the endpoint definition, observed event counts, interval width, analysis method, and the trial's design. Here, the record supports describing the observed counts and their uncertainty, but does not support inferring unreported details of the statistical plan.

11. Confidence Intervals and Precision

The primary recalculated risk difference is 0.006, with a 95% confidence interval from -0.034 to 0.047. The interval spans zero, so the posted data are compatible with a small difference in either direction as well as no difference. Its breadth relative to the point estimate indicates limited precision for the absolute contrast. The interval should not be read as a range of effects guaranteed to contain the true value.

The sponsor-reported risk ratio is 0.83, with a 95% confidence interval from .26 to 2.67. This interval spans one, the reference value for equal relative risks, and includes substantially different relative contrasts. The primary endpoint has only 5 and 6 positive events in the two analyzed groups, which contributes to the uncertainty apparent in the intervals.

Confidence intervals depend on the analysis method and assumptions. The registry identifies a chi-squared analysis for the sponsor-reported risk ratio; the record does not provide further diagnostics or methods details. The recalculated interval is an unadjusted estimate based on the posted summary counts. These intervals are not interchangeable because they refer to different effect measures. Together, they show that the observed point estimates alone should not be treated as highly precise estimates of the underlying group contrast.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not a reconstruction of the trial's original design. For this binary endpoint, the figures are participants per arm. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each illustration uses the stated fraction of the observed effect as the effect to detect. The original trial's sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding planning count for a higher chance of detection. These are design calculations, not evidence about the power achieved by the completed trial. This is not observed power.

The rows use the full observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects are harder to distinguish from random variation, so planning for a smaller effect requires more participants per arm. The listed numbers therefore grow as the assumed fraction of the observed effect becomes smaller. The illustrations should be interpreted cautiously because the observed effect comes from a trial with few primary events and is itself uncertain. A planning calculation based on that estimate does not show that the effect is stable or clinically important.

The sample-size curve is another way to read the relationship between assumed effect and required enrollment under the stated assumptions. It does not supply a new result about the treatment comparison. The displayed planning figures apply to the particular primary summary used in the calculation and should not be treated as the actual enrollment target unless the registry record documents that design choice; it does not.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.032; treatment proportion p₁ = 0.038; average p̄ = 0.035.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.2592 = 0.5081.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.2592 = 0.2181.
4. n = (0.5081 + 0.2181)² / (0.0063)² = 13,165.3, rounded up to 13,166 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0316455696202532                          # control proportion
p1 <- 0.0379746835443038                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(993031)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 13,166 (80% power), 17,625 (90% power)
 75% of observed effect: n per arm = 22,893 (80% power), 30,647 (90% power)
 50% of observed effect: n per arm = 50,354 (80% power), 67,409 (90% power)
power.prop.test: 13165.3 
Simulated power at n = 13,166 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor's primary comparison as a chi-squared analysis of the risk ratio: 0.83, with a 95% confidence interval from .26 to 2.67 and p = .76. The unadjusted recalculation from the posted counts gives a risk difference of 0.006, with a 95% confidence interval from -0.034 to 0.047 and p = 0.759. The two estimates use different effect scales, so their point estimates are not expected to match numerically. Their p-values are close and lead to a similar broad interpretation of the recorded primary data.

The recalculation uses only the posted event counts and denominators. It cannot reproduce an analysis requiring information not contained in those summaries. The registry record does not describe further adjustments or other analysis details. For interpreting the trial's reported result, the sponsor's own analysis is the principal reported analysis; the recalculation is a transparent, simple comparison of the summary counts, not a substitute for the sponsor's analysis.

The reported risk-ratio interval is broad and includes one. The recalculated risk-difference interval is also broad and includes zero. Both presentations therefore emphasize uncertainty rather than a precise separation of the groups. Neither the similarity of the p-values nor the overlap with the reference values demonstrates that the regimens have identical effects.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists numerous outcome measures and five analyses, including the primary comparison and several secondary outcomes. When many outcomes or comparisons are examined, the chance of obtaining at least one apparently unusual result by chance can increase. Statistical procedures or a prespecified hierarchy can address this concern, but the registry record does not report a multiplicity adjustment, a testing hierarchy, or how the investigators intended to distinguish confirmatory from exploratory findings. The secondary results should therefore be interpreted cautiously, especially when considered individually.

The record does not report the original statistical analysis plan, details of interim analyses, or a complete account of the planned analysis populations. It does not state whether the primary analysis followed intention-to-treat, per-protocol, or another population definition. Randomization is recorded, but details of allocation concealment and the handling of deviations from assigned treatment are not reported in the registry record.

The primary analysis includes 158 participants in each group, while overall enrollment was 389. Endpoint-specific denominators also vary across the posted secondary results. Such differences can arise for many reasons, but the registry record does not explain them. It does not report how many endpoint values were missing, why they were missing, whether missingness differed by group, or whether any imputation or sensitivity analyses were performed. The available counts should thus be understood as the participants represented in the posted outcome data, not assumed to represent every enrolled participant.

These omissions limit assessment of the robustness of the estimates. They do not establish that the analysis was inappropriate; they mean that the registry record alone does not permit a detailed evaluation of multiplicity control, missing-data handling, or analysis-population choices.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (4.6%), severe anemia (3.6%), intra-uterine fetal death (3.1%), pyelonephritis (1.5%), thrombocytopenia (1.5%).

The registry lists serious adverse events for Group A among 194 participants at risk, with 28 participants affected, and for Group B among 195 participants at risk, with 32 affected. It also reports other adverse events for 140 of 194 participants in Group A and 137 of 195 in Group B. These are participant counts in the posted safety record; they are not event totals, and the record does not provide a comparative statistical analysis for them.

The listed serious adverse event terms include neutropenia at 4.6%, severe anemia at 3.6%, intra-uterine fetal death at 3.1%, pyelonephritis at 1.5%, thrombocytopenia at 1.5%, and preterm contractions at 1.5%. The record does not give group-specific percentages for these listed terms. Death counts are not reported in the registry record.

These descriptive figures should not be interpreted as a formal comparison of safety between regimens. The registry record does not report further detail about event severity classifications beyond the serious-event listing, exposure duration, or comparative statistical methods for adverse events.

17. What the Result Does, and Does Not, Mean

The primary result describes a randomized comparison of placental blood-smear malaria at delivery among participants with posted outcome data. The observed counts were 5 of 158 with protease inhibitor-based therapy and 6 of 158 without it. The reported and recalculated estimates are imprecise: their confidence intervals include the reference value for no group difference on their respective scales.

This means the posted primary analysis does not provide strong evidence of a difference between the groups. It does not show that the regimens have exactly the same effect, and it does not establish that either regimen is superior or inferior. The intervals allow a range of possible underlying contrasts, and the sparse event counts make the point estimates uncertain.

The result applies to the endpoint as defined in the registry: a positive placental blood smear at delivery. It does not by itself establish what would be seen for rapid diagnostic testing, histopathology, maternal malaria treatments, composite pregnancy outcomes, or other secondary measures. Those outcomes have their own definitions and analysis populations.

The record also does not provide enough information to assess all aspects of missing data, multiplicity, or the original statistical plan. The estimates should therefore be understood as the results of the posted analyses rather than as a complete account of every possible analysis. They describe observed data and statistical uncertainty; they are not medical advice and do not establish a treatment recommendation.

18. Why This Trial Matters Statistically

Statistically, this trial illustrates why a randomized design and an informative endpoint do not automatically yield a precise estimate. The primary comparison was randomized, but the posted placental blood-smear counts are sparse. With few events, even modest changes in the observed counts can affect the estimated contrast, and the resulting confidence intervals can remain broad.

It also illustrates the importance of distinguishing effect measures. The registry reports a relative measure, the risk ratio, while an unadjusted recalculation expresses the contrast as an absolute risk difference. Each scale answers a related but distinct descriptive question. Considering both helps readers avoid treating a single point estimate as a complete account of the data.

The record lists several secondary outcomes using different definitions and assessment methods. Their differing results underline why endpoints should not be collapsed into one general label such as placental malaria without attention to how each was measured. Multiple secondary analyses also require care: without reported multiplicity procedures or a hierarchy, isolated findings are less persuasive than the primary comparison.

Finally, registry transparency matters for interpretation. The record gives the main endpoint counts and sponsor-reported analysis, but does not report important details such as the original sample-size justification, missing-data handling, or full analysis populations. Those gaps limit how far readers can evaluate the analysis beyond the posted results. The trial is statistically informative not because its estimate is conclusive, but because it shows how endpoint definitions, sparse events, precision, and reporting completeness shape interpretation.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to interpreting this registry record. The primary endpoint is based on placental blood-smear status at delivery, and the posted analysis includes 158 participants in each group despite overall enrollment of 389. The record does not explain the difference between those counts or report the number and reasons for missing placental assessments. The primary estimate therefore cannot be assumed to represent every enrolled participant.

The primary outcome has few positive events, and its confidence intervals are broad. This limits precision and makes the observed point estimates sensitive to small changes in event counts. The registry record does not report the original sample-size justification, so it is not possible to determine from this record whether the planned design targeted the primary contrast with a particular precision.

The trial is listed as open-label and single-site. The registry does not describe allocation concealment, blinded endpoint assessment, or details that would permit evaluation of their role. It also does not provide the full statistical analysis plan, the handling of missing data, or the analysis-population definition. These are reporting limitations; they do not by themselves demonstrate bias.

Secondary outcomes use distinct definitions and have varying denominators. The record does not report a multiplicity strategy, and the secondary findings should not be treated as though they were a single confirmatory test. Safety information is descriptive, with no posted comparative analysis and no death counts reported. These features constrain the scope of conclusions that can be drawn from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women — NCT00993031.
• Registry record last updated 2019-05-14; status last verified 2019-04.
• Results first posted 2017-12-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry record describes a completed, randomized, parallel-group, open-label, single-site phase 3 trial sponsored by the University of California, San Francisco. It enrolled 389 participants and compared protease inhibitor-based antiretroviral therapy with non-protease inhibitor-based therapy in HIV-infected pregnant women at high risk of malaria.

The primary endpoint was positive placental blood smear at delivery. The posted counts were 5 of 158 in the protease inhibitor group and 6 of 158 in the group without a protease inhibitor. The sponsor-reported risk ratio was 0.83, with a 95% confidence interval from .26 to 2.67 and p = .76. The interval is broad and includes the reference value for equal relative risks.

The record also lists secondary placental, maternal, pregnancy, and infant-related outcomes, as well as descriptive adverse-event counts. Details of the original sample-size justification, missing-data handling, multiplicity procedures, and analysis populations are not reported in the registry record.