Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (NCT01802385), a randomized phase 3 study. The primary outcome is Survival.

2. Clinical Question

3. Trial Design

This was a phase III, randomized, quadruple-masked, parallel-group trial of adjunctive sertraline for HIV-associated cryptococcal meningitis. The registry lists University of Minnesota as the sponsor and records the study status as completed. The recorded start was 2015-03-09, and primary completion was 2017-09. Enrollment was 460.

The two groups were placebo and Sertraline 400mg. Both groups received the described standard cryptococcal meningitis therapy; sertraline was added in the experimental group, while placebo was added in the comparator group. The registry describes the sertraline schedule as 400mg/day for 2 weeks, then 200mg for 12 weeks, followed by tapering over 3 weeks. It describes standard treatment as amphotericin at 0.7-1.0 mg/kg/day and fluconazole at 800-1200mg/day.

The primary outcome was survival at 18 weeks, compared between the sertraline and placebo groups. The registry also lists outcomes covering safety, cerebrospinal fluid sterility, depression, neurocognitive performance, fungal clearance, IRIS or relapse, and event-free survival. Numerical comparative results are posted for a subset of these outcomes.

The registry record does not report the original sample-size justification, the intended allocation ratio, or the full protocol. It also does not report the trial's detailed analysis plan or whether interim analyses were planned. The planning illustrations associated with the posted results are separate from the trial's original design assumptions.

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:

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 Survival, measured over 18 weeks.

The primary endpoint is the count of participants surviving at 18 weeks. Survival at a defined follow-up time is a binary outcome for each participant: the participant is recorded as alive or not alive at the specified time. The group counts therefore describe how many participants met the survival outcome, rather than the duration of survival or the timing of events during follow-up.

Survival is directly relevant to the trial's stated question about whether adjunctive sertraline would improve 18-week survival in people receiving standard cryptococcal meningitis therapy. Comparing the proportion meeting this endpoint in each randomized group gives an interpretable summary of the outcome at the chosen time point. It does not, by itself, describe when deaths occurred or account for differences in follow-up time.

The posted primary results report 125 participants with survival in the placebo group and 109 in the Sertraline 400mg group. The unadjusted risk-difference estimate is negative, with the direction indicating a lower observed survival proportion in the sertraline group. Its confidence interval includes no difference, and the unadjusted p-value is 0.162. These results should be read as a comparison of the posted endpoint counts, not as proof of a treatment effect or of no treatment effect.

The registry record does not report further endpoint definitions, such as the handling of participants whose status at 18 weeks was unknown. That missing detail limits how fully the endpoint's ascertainment and analysis can be assessed.

7. Results Posted in the Registry

• Sertraline 400mg: 47.6% (109/229) versus 54.1% (125/231) on control; risk difference -6.5 percentage points (95% CI -15.6 to 2.6), risk ratio 0.88 (0.73–1.05); unadjusted two-proportion z-test p = 0.162.

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.

Count of Participants With Cerebrospinal Fluid Sterility

• 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:
  • Sertraline 400mg: 44.1% (101/229) versus 39.0% (90/231) on control; risk difference 5.1 percentage points (95% CI -3.9 to 14.1), risk ratio 1.13 (0.91–1.41); unadjusted two-proportion z-test p = 0.263.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sertraline 400mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants Experiencing IRIS OR Relapse

• 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:
  • Sertraline 400mg: 2.2% (5/229) versus 3.9% (9/231) on control; risk difference -1.7 percentage points (95% CI -4.8 to 1.4), risk ratio 0.56 (0.19–1.65); unadjusted two-proportion z-test p = 0.285.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sertraline 400mg and the control. The interval gives the range of effects that remain compatible with the data.

Event Free Survival

• 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:
  • Sertraline 400mg: 45.0% (103/229) versus 50.2% (116/231) on control; risk difference -5.2 percentage points (95% CI -14.4 to 3.9), risk ratio 0.90 (0.74–1.09); unadjusted two-proportion z-test p = 0.261.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sertraline 400mg and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning sterility of cerebrospinal fluid, IRIS or relapse, event-free survival, safety, depression, neurocognitive performance and fungal clearance. The posted numerical comparisons cover only a subset of those listed outcomes. Across the available comparisons, the estimated directions are not uniformly aligned: some point toward a higher observed outcome proportion with sertraline, while others point toward a lower proportion. Their confidence intervals include no difference, and their unadjusted p-values do not provide clear evidence of separation between groups.

These outcomes address different aspects of illness and follow-up, so they should be treated as complementary rather than interchangeable measures of the primary question. The primary endpoint is survival at 18 weeks. A difference in a secondary measure would not, by itself, establish a difference in survival, and a lack of a clear secondary contrast does not resolve the uncertainty in the primary result. The secondary findings do not overturn the primary comparison; they provide additional, but limited, context.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities for an apparently notable result to arise by chance. No multiplicity adjustment or prespecified testing hierarchy is reported in the registry record. The record also reports no analysis listings for these outcomes. Thus, the available comparisons should be interpreted cautiously, particularly when deciding whether an isolated pattern is reproducible or clinically meaningful.

The registry record does not report results for every listed secondary measure in the numerical comparisons. Absence of a posted result is not evidence that the outcome was not measured or that no effect occurred. It means that the record does not allow the same quantitative assessment for those outcomes. In general, secondary outcomes are most informative when their definitions, analysis methods and place in a prespecified testing strategy are clear.

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

• Safety (Occurence of Adverse Events)
• Count of Participants With Cerebrospinal Fluid Sterility
• Center for Epidemiologic Studies in Depression (CES-D) Scale
• Quantitative Neurocognitive Performance Score (QNPZ-8)
• Fungal Clearance as Determined by Early Fungicidal Activity of CDF
• Number of Participants Experiencing IRIS OR Relapse
• Event Free Survival

9. Statistical Interpretation

10. Statistical Methods Explained

The main comparison is a risk difference: the observed risk of the endpoint in the sertraline group minus the observed risk in the placebo group. For a binary outcome such as survival at 18 weeks, the risk in a group is the proportion of that group meeting the endpoint. A negative risk difference means the observed proportion is lower in the sertraline group; a positive value would mean it is higher. This direction describes the contrast and does not establish a causal explanation on its own.

What does the confidence interval describe?

A confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical method. It gives a range of effect sizes that are reasonably compatible with the data and method; it is not a guarantee that the true effect lies inside the particular interval. For the primary comparison, the interval includes no difference. This means the posted data do not distinguish the estimate from no difference at the interval's stated confidence level. The interval also allows for effects in either direction, so the estimate should not be interpreted as a precise measure of the underlying effect.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.162. In general, a p-value measures how unusual data at least as incompatible with a specified no-difference model would be if that model and the analysis assumptions were true. It is not the probability that the treatment works, the probability that the null hypothesis is true, or a measure of clinical importance. An unadjusted p-value also does not account for the possibility of examining multiple outcomes or analyses. The registry record does not report a multiplicity adjustment or a prespecified testing hierarchy.

The risk-difference estimate and its interval are recalculated from the posted group summaries. They are simple unadjusted comparisons and are not a substitute for a sponsor's prespecified analysis. No discrepancy is indicated in the registry record. The record does not list a sponsor-reported analysis or an adjusted model for the primary outcome, so the recalculated comparison should be read as a transparent summary of the posted counts.

What do the group counts represent?

For this primary endpoint, the counts are participants recorded as surviving at 18 weeks. The denominator is the number assigned to each posted group, but a count comparison alone does not explain whether all randomized participants had outcome status available. Details about missing status, censoring, exclusions, or the analysis population are not reported in the registry record. Those choices can matter because they determine which participants contribute to a comparison and how outcome status is interpreted.

The registry labels the design randomized, quadruple-masked and parallel-group. Randomization is intended to make the treatment groups comparable at assignment, while masking is intended to reduce the influence of knowledge of assignment on care, assessment or reporting. These design labels do not show whether masking was maintained or whether all analytic assumptions were met; those details are not reported in the registry record. The reported endpoint is a fixed-time count, not a survival curve or a hazard ratio.

Why is over-dispersion not central to this endpoint?

Over-dispersion is a concern when observed variation in a count or rate is greater than a model assumes, often because observations are correlated or the count-generating process is more variable than expected. The primary outcome is reported as the number of participants meeting a binary endpoint, and the posted comparison uses a risk difference. The registry record does not describe a count model or a dispersion parameter for this endpoint. It would therefore be inappropriate to infer that an over-dispersion adjustment was used or was needed. More generally, analyses of clustered, repeated or rate outcomes may need methods that account for dependence or excess variability; that is a general statistical consideration, not a feature reported for this primary comparison.

The registry also lists secondary binary outcomes with unadjusted comparisons. Each additional outcome can provide context, but separate unadjusted tests do not control the overall chance of a false-positive finding across a set of tests. The record does not report a correction, hierarchy, or other strategy for interpreting multiple comparisons. The secondary results should consequently be treated as exploratory unless a prespecified analysis plan establishes otherwise.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate the effect, rather than whether the point estimate points in a particular direction. The primary risk-difference confidence interval spans no difference. Thus, although the point estimate favors the placebo group in the observed counts, the data are also compatible with no difference and with a contrast in the other direction. The interval's width indicates that the estimate is not precise enough to settle the direction of the underlying difference.

The confidence interval is more informative than the point estimate alone because it displays the range of uncertainty associated with the estimate. It should not be read as a range of individual outcomes, nor as the probability that a treatment effect has a particular value. The posted interval depends on the calculation method and the underlying analysis assumptions. The registry record does not give a detailed statistical analysis plan or report an adjusted estimate for the primary outcome.

The p-value of 0.162 is consistent with the interval including no difference, but it does not measure the size or clinical importance of the effect. A result that does not meet a chosen significance threshold can still be compatible with a meaningful effect in either direction when uncertainty is substantial. Conversely, the observed point estimate should not be treated as the true effect merely because it is the best single estimate available.

The posted group counts are the basis for the simple comparison, but missing-data handling and analysis-population details are not reported in the registry record. Without those details, readers cannot fully evaluate whether the stated interval reflects all randomized participants or a subset with available outcome status. Precision should therefore be interpreted alongside the design information and the limits of the posted analysis, not as a complete account of uncertainty in every aspect of the trial.

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 planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total enrollment targets. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to a stated fraction of the observed effect. The illustrations use 100% of the observed effect, 75% of the observed effect and 50% of the observed effect.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the specified effect at the stated significance level, if that effect were the true one and the assumptions held. The 90% column describes the corresponding higher chance of detection. These are design concepts, not probabilities that the trial result is true. The displayed figures are planning illustrations based on the observed effect, not the trial's original sample-size justification.

The figures increase as the effect to be detected becomes smaller: a study generally needs more participants to distinguish a modest difference from random variation than a larger difference. The accompanying curve expresses that relationship across the assumed effect sizes. The projections depend on the planning assumptions and should not be interpreted as a guaranteed sample size for a future study; different outcome rates, methods or design choices could change the requirement.

This is not observed power. Observed power is not a useful replacement for reading the estimated effect and its confidence interval: the planning calculation illustrates what would be needed under specified assumptions, while the trial's uncertainty is conveyed by the posted result and interval.

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 = 0.541; treatment proportion p₁ = 0.476; average p̄ = 0.509.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7070 = 1.3857.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7055 = 0.5938.
4. n = (1.3857 + 0.5938)² / (-0.0651)² = 923.3, rounded up to 924 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 <- 0.541125541125541                          # control proportion
p1 <- 0.475982532751092                          # 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(1802385)
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 = 924 (80% power), 1,236 (90% power)
 75% of observed effect: n per arm = 1,642 (80% power), 2,197 (90% power)
 50% of observed effect: n per arm = 3,689 (80% power), 4,938 (90% power)
power.prop.test: 923.3 
Simulated power at n = 924 per arm: 0.796 (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. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons or analyses are examined. Even when each test is interpreted at a conventional threshold, carrying out many tests increases the chance that at least one will appear notable by chance. This matters in this trial because the registry lists multiple secondary outcomes in addition to the primary survival endpoint. The registry record does not report a multiplicity adjustment, a hierarchical testing strategy, or another prespecified approach for controlling the interpretation of multiple comparisons. The secondary p-values are therefore unadjusted and should not be treated as confirmatory evidence on their own.

The analysis record lists no reported analyses. The posted comparisons are unadjusted recalculations from the group summaries, and the registry does not report a detailed protocol-specified statistical plan, adjusted primary model, or interim-analysis plan. The original sample-size justification and its design assumptions are not reported in the registry record. These omissions make it difficult to determine whether the posted comparisons match the originally intended primary analysis or how the trial planned to address multiple outcomes.

Missing-data methods are also not reported in the registry record. For the primary outcome, the posted counts do not explain how participants with unknown survival status were handled, whether follow-up was complete, or whether any imputation or sensitivity analysis was used. The record does not describe an intention-to-treat, per-protocol or other analysis population. These are important distinctions: analysis populations and missing-data choices can affect which observations enter an estimate and how robust the result is to incomplete follow-up.

The absence of these details does not demonstrate that the trial used inappropriate methods. It limits independent assessment of the methods and their potential effect on the results. A full interpretation would benefit from the prespecified analysis plan, endpoint ascertainment details, missing-data procedures and any sponsor-reported primary analysis. Until those are available in the registry record, the posted unadjusted comparisons should be read as descriptive estimates with the stated uncertainty, rather than as a complete report of all planned analyses.

15. Safety Results

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

Deaths

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: anemia (23.6%), hyponatremia (7.0%), elevated creatinine (5.7%), hypokalemia (5.7%), lymphopenia (4.4%).

The registry lists serious adverse events affecting 121 participants in the placebo group and 141 in the Sertraline 400mg group. These are counts, not adjusted comparisons, and the record does not provide a statistical analysis of the between-group safety difference. The counts should not be interpreted as showing that treatment caused a difference: they do not account for event timing, severity, exposure duration or other details of ascertainment.

The listed serious-event terms include Anemia at 23.6%, Hyponatremia at 7.0%, Elevated Creatinine at 5.7%, Hypokalemia at 5.7%, Lymphopenia at 4.4% and Elevated Bilirubin at 4.3%. The registry excerpt does not specify the denominator or whether these term percentages apply to a particular group, so they should be read as listed rather than used for an arm-to-arm comparison.

The registry also records deaths by group, but the serious adverse event counts and death counts are distinct reported measures and should not be conflated. Without further definitions, timing, exposure information and adjusted analyses, these safety summaries describe what was recorded but do not establish a causal safety effect.

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

The posted primary result describes survival at 18 weeks in the two randomized groups. The observed count was 125 in the placebo group and 109 in the Sertraline 400mg group. The unadjusted risk-difference estimate points toward a lower survival proportion in the sertraline group, but its confidence interval includes no difference and the p-value is 0.162. This is an uncertain comparison, not a definitive estimate of a treatment effect.

The result does not establish that sertraline improves survival, and it does not establish that sertraline reduces survival. The interval's inclusion of no difference is not proof that the groups are equivalent. Equivalence or non-inferiority requires a specific design, margin and analysis; those are not reported in the registry record. A nonsignificant result is also not evidence that every clinically meaningful effect has been ruled out.

The endpoint is survival at a fixed follow-up time. It does not describe the timing of deaths, later outcomes, or the full course of illness. The registry's secondary outcomes address other domains, but their unadjusted comparisons do not replace the primary endpoint or settle its uncertainty. The results also cannot be generalized beyond the population and treatment context described in the registry without additional evidence.

The trial was randomized and masked according to the registry, which are relevant design features. However, important analysis details—including missing-data handling, analysis population and the original statistical plan—are not reported in the registry record. The posted estimates therefore support a cautious description of the observed data, not a broad conclusion about treatment efficacy or safety. Clinical decisions should not be based on this statistical summary alone.

17. Why This Trial Matters Statistically

This trial is statistically informative because it poses a direct randomized comparison of an adjunctive treatment against placebo while both groups receive the described standard therapy. Its primary endpoint, survival at 18 weeks, is a clear fixed-time outcome, and the registry posts group counts that allow a simple unadjusted contrast. Reporting an estimate with a confidence interval makes the uncertainty visible rather than leaving interpretation to the observed counts alone.

The result also illustrates why direction and certainty must be considered together. The point estimate favors the placebo group, but the interval includes no difference and the p-value is 0.162. A reader should neither equate the point estimate with a settled treatment effect nor interpret the absence of a statistically clear difference as proof of equivalence. The interval is central to understanding how limited the precision is.

The registry lists a range of secondary outcomes, reflecting that treatment effects may be assessed across multiple domains. Yet unadjusted results across multiple outcomes require care: without a reported multiplicity strategy, isolated findings can be misleading. The registry's lack of a detailed analysis plan, missing-data approach and analysis-population definition further illustrates why a numerical estimate is only one part of evaluating a trial.

Finally, the sample-size illustrations show how planning depends on the effect size one aims to detect and on assumptions about allocation and statistical testing. They are not a substitute for the original design rationale or an indication of the trial's observed power. Together, the design and posted results offer a useful setting for distinguishing a trial's observed comparison, its uncertainty, and the limitations of what a registry record can establish.

18. 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 specific to interpretation arise from the registry record. The primary outcome is described as 18-week survival, but further details about ascertainment, the handling of unknown status and completeness of follow-up are not reported in the registry record. The posted counts therefore cannot, on their own, establish how missing outcome information was treated or which analysis population was used.

The primary comparison is an unadjusted recalculation from posted group summaries. The record lists no reported analyses and does not provide a protocol-specified statistical plan, adjusted estimate, original sample-size justification, or interim-analysis plan. As a result, readers cannot verify the planned analysis or assess whether any additional analyses changed the interpretation.

The trial includes multiple secondary outcomes, but the registry record does not report a multiplicity adjustment or testing hierarchy. Numerical comparisons are available for only a subset of the listed measures, limiting a complete assessment of the outcome set. Unadjusted secondary findings should consequently be regarded as less conclusive than a prespecified primary analysis.

The safety summaries are counts and listed terms, without the detailed definitions and comparative analyses needed to assess causality. The record does not establish the event timing, exposure-adjusted rates or group-specific interpretation of the listed serious-event percentages. The fixed-time primary endpoint also does not convey time-to-event information. These limitations do not invalidate the posted results, but they constrain how strongly they can support conclusions beyond the observed group summaries.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis — NCT01802385.
• Registry record last updated 2020-06-09; status last verified 2020-06.
• Results first posted 2020-01-13.
• 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.

22. Record Summary

The registry record describes a completed phase III randomized, quadruple-masked, parallel-group trial sponsored by University of Minnesota. It compared adjunctive sertraline with placebo alongside standard cryptococcal meningitis therapy in people with HIV-associated cryptococcal meningitis. Enrollment was 460.

The primary outcome was survival at 18 weeks. The posted counts were 125 in the placebo group and 109 in the Sertraline 400mg group. The unadjusted comparison points toward a lower observed survival proportion with sertraline, but its confidence interval includes no difference and its p-value is 0.162. The record also lists secondary outcomes and safety counts, but does not report key details of the analysis plan, missing-data handling or analysis population. The findings describe the posted data and their uncertainty; they do not establish a definitive treatment effect.