Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016) (NCT04003103), a randomized phase 2 study. The primary outcome is Number of Participants With ≥1 Adverse Event (AE) Through Week 36.

2. Clinical Question

The statistical comparison is between each islatravir dose group and the placebo group. It concerns the frequency of participants with one or more recorded adverse events, rather than the total number of event episodes or the severity of every event. The registry also lists safety outcomes through Week 24 and pharmacokinetic outcomes, including plasma concentration measures. The primary result therefore addresses a specific safety count over the stated follow-up period; it does not by itself describe every aspect of tolerability, drug exposure, or longer-term outcomes.

3. Trial Design

This was a Phase 2a randomized, double-blind, placebo-controlled, parallel-group study. The registry record identifies Merck Sharp & Dohme LLC as the sponsor and lists enrollment of 242 participants. The study is marked completed. The recorded study start was 2019-09-19, and the primary completion date was 2022-03-18.

Participants were assigned to one of three groups: islatravir 60 mg, islatravir 120 mg, or placebo. Each intervention was administered orally once monthly in capsule form for 24 weeks. The 60 mg group is described as receiving 60 mg islatravir plus placebo for islatravir; the 120 mg group received 120 mg islatravir; and the placebo group received placebo for islatravir. Double masking means the registry identifies the study as blinded for two parties, but it does not report further details about who was masked or how masking was maintained.

The primary safety outcome counts participants with at least one adverse event through Week 36. The stated primary population comprises all participants who received at least one dose of study therapy. Secondary outcomes include adverse-event counts through Week 24 and several pharmacokinetic measures. The record lists 20 outcome measures and reports no analyses in its analysis listing. Further details about the allocation procedure, stratification, planned analysis methods, and original sample-size justification are not reported in the registry record.

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: All participants who received ≥1 dose of study therapy are included.

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 Number of Participants With ≥1 Adverse Event (AE) Through Week 36, measured over Up to 36 weeks.

The primary endpoint is the number of participants with at least one adverse event through Week 36. An adverse event is defined in the registry record as an untoward medical occurrence in a clinical study participant that is temporally associated with study intervention, whether or not it is considered related to the intervention. The endpoint is a participant count: a participant is counted if at least one qualifying event occurred during the stated period. It does not indicate how many distinct events each participant experienced.

A count of participants with one or more events is useful for describing how commonly participants experienced any recorded adverse event in each randomized group. Comparing these counts can convey the observed difference between groups without treating repeated events in one participant as if they came from different people. The endpoint does not, on its own, distinguish events by seriousness, severity, or attribution to treatment. Those features require separate outcomes or event descriptions.

The primary endpoint is measured through Week 36, while the intervention description specifies monthly dosing for 24 weeks. The registry record does not provide further detail about the timing of individual event assessments or the handling of events for participants with incomplete follow-up. The posted counts should therefore be read as the registry’s reported results for this endpoint and timeframe, not as a complete characterization of all safety dimensions.

7. Results Posted in the Registry

• Islatravir 60 mg: 68.0% (66/97) versus 75.0% (36/48) on control; risk difference -7.0 percentage points (95% CI -22.3 to 8.4), risk ratio 0.91 (0.73–1.12); unadjusted two-proportion z-test p = 0.388.
• Islatravir 120 mg: 64.9% (63/97) versus 75.0% (36/48) on control; risk difference -10.1 percentage points (95% CI -25.6 to 5.4), risk ratio 0.87 (0.70–1.08); unadjusted two-proportion z-test p = 0.221.

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.

Number of Participants With ≥1 AE Through Week 24

• 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:
  • Islatravir 60 mg: 59.8% (58/97) versus 66.7% (32/48) on control; risk difference -6.9 percentage points (95% CI -23.4 to 9.7), risk ratio 0.90 (0.69–1.16); unadjusted two-proportion z-test p = 0.422.
  • Islatravir 120 mg: 61.9% (60/97) versus 66.7% (32/48) on control; risk difference -4.8 percentage points (95% CI -21.3 to 11.7), risk ratio 0.93 (0.72–1.20); unadjusted two-proportion z-test p = 0.571.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Islatravir 60 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Islatravir 120 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With ≥1 Drug-related AE Through Week 24

• 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:
  • Islatravir 60 mg: 9.3% (9/97) versus 25.0% (12/48) on control; risk difference -15.7 percentage points (95% CI -29.3 to -2.2), risk ratio 0.37 (0.17–0.82); unadjusted two-proportion z-test p = 0.011.
  • Islatravir 120 mg: 14.4% (14/97) versus 25.0% (12/48) on control; risk difference -10.6 percentage points (95% CI -24.7 to 3.5), risk ratio 0.58 (0.29–1.15); unadjusted two-proportion z-test p = 0.119.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Islatravir 60 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Islatravir 120 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With ≥1 SAE Through Week 24

• 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:
  • Islatravir 60 mg: 1.0% (1/97) versus 0.0% (0/48) on control; risk difference 1.0 percentage points (95% CI -1.0 to 3.0); unadjusted two-proportion z-test p = 0.480.
  • Islatravir 120 mg: 0.0% (0/97) versus 0.0% (0/48) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Islatravir 60 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Islatravir 120 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the description beyond the primary count through Week 36. They include adverse-event counts through Week 24, drug-related adverse events, serious adverse events, higher-grade adverse events, and pharmacokinetic measures such as plasma exposure, maximum concentration, trough concentration, and apparent terminal half-life. The registry record lists 11 posted secondary outcomes, but it does not provide numerical results for every outcome named in the record.

Across the posted Week 24 adverse-event counts, the unadjusted group contrasts do not form a single uniform pattern. The broad any-adverse-event outcome and the drug-related outcome describe different classifications, while serious events are sparse. Those distinctions matter: a lower count on one secondary outcome does not imply a consistent direction across all safety dimensions, and a drug-related classification is not interchangeable with the broader adverse-event definition used for the primary endpoint. The primary result is a Week 36 count, so the Week 24 secondary results also differ in follow-up period.

Secondary results are generally less definitive than a single primary comparison when many outcomes or contrasts are considered. Unless a testing plan and multiplicity procedure are specified, unadjusted secondary p-values do not account for the chance of finding an apparently notable result among multiple comparisons. The registry record does not report a multiplicity strategy or sponsor-reported analyses for the posted secondary outcomes. Any individual unadjusted secondary result should therefore be treated as descriptive and interpreted in context, rather than as independent confirmatory evidence.

The pharmacokinetic outcomes address drug exposure rather than event frequency. Their presence in the outcome list does not establish a relationship between exposure and safety, and the record does not report numerical results for each named measure in the information summarized by the posted adverse-event comparisons. The overall secondary pattern is best understood as a set of distinct supporting observations with different measures and timeframes, not as a single combined test of the primary question.

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

• Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL
• Maximum Plasma Concentration (Cmax) of ISL
• Trough Plasma Concentration (Ctrough) of ISL
• Apparent Plasma Terminal Half-life (t1/2) of ISL
• Number of Participants With ≥1 AE Through Week 24
• Number of Participants With ≥1 Drug-related AE Through Week 24
• Number of Participants With ≥1 SAE Through Week 24
• Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The results are counts of participants who experienced at least one event, not continuous measurements. For each group, the registry gives the number of participants with the outcome and the group size. A risk difference expresses the difference between the two group event proportions, with the comparison framed as islatravir minus placebo. A negative value therefore corresponds to a lower observed proportion in the islatravir group; a positive value corresponds to a higher observed proportion. This is a general interpretation of the statistic, not a claim about causation.

What does an interval around a risk difference convey?

In general, a confidence interval describes the range of values reasonably compatible with the observed data under the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while an interval that includes zero leaves a no-difference value among the compatible possibilities. An interval is not a guarantee that the true value lies within its endpoints, and it does not remove limitations arising from the study design, incomplete reporting, or the choice of analysis. The registry lists interval endpoints but does not report the confidence level or the detailed method used for the primary comparison.

How should the p-values be read?

The p-values accompanying the risk-difference comparisons are labeled unadjusted. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a difference. A p-value should be interpreted with the point estimate, its interval, and the analysis plan. The registry record does not report the sponsor’s planned inferential procedure or a multiplicity adjustment, so the posted unadjusted p-values should not be read as evidence of a prespecified confirmatory testing strategy.

What is the role of the group counts?

The observed counts show how many participants met the endpoint in each group. They retain the participant as the unit of analysis, which is appropriate for an outcome defined as having at least one event. This approach does not describe recurrent-event burden: a participant with one event and a participant with multiple events both contribute one person to the count. Other outcomes, such as total event numbers or time until an event, would answer different questions, and their analyses are not reported for this primary endpoint.

What does unadjusted recalculation mean?

The risk differences, intervals, and p-values are simple unadjusted recalculations from the posted summary statistics. They compare the reported group counts without a reported adjustment for baseline characteristics or other covariates. The registry record does not report adjusted analyses for these comparisons. Unadjusted calculations can be helpful for understanding the contrast visible in the posted data, but they do not establish that the sponsor used the same method or that the calculation follows the original protocol. No discrepancy between these calculations and a sponsor analysis is flagged in the record; no sponsor analysis is listed for comparison.

For binary outcomes, uncertainty depends on the event counts and group sizes. In general, sparse counts can make estimates unstable and intervals less informative, particularly when an outcome is absent in one or more groups. This general concern applies when interpreting the secondary serious-adverse-event counts, where very few participants are reported with an event. The methods and assumptions used for those secondary comparisons are not detailed in the registry record.

Finally, an outcome’s time window and population are part of its statistical definition. The primary count is reported through Week 36 and includes participants who received at least one dose. The secondary adverse-event outcomes use a Week 24 timeframe. Those results should not be assumed to represent identical follow-up or identical analysis populations. The record does not report imputation procedures, censoring rules, or other missing-data methods. Such details can affect the interpretation of a count when follow-up is incomplete, so the posted summaries should be read without assuming a particular handling approach.

11. Confidence Intervals and Precision

The primary risk-difference interval for 60 mg runs from -0.223 to 0.084. For 120 mg, it runs from -0.256 to 0.054. Each interval includes zero, so the posted data do not pin down the direction of the underlying difference with precision. The ranges also include values on both sides of zero, meaning the observed point estimates alone do not rule out either a lower or a higher event proportion relative to placebo.

The intervals are wide in relation to their point estimates. This indicates substantial uncertainty in the size of the group contrasts, even though the estimates themselves are negative. The placebo group has 48.0 participants, compared with 97.0 in each islatravir group; the registry does not report a rationale for the allocation sizes or a precision target. The difference in group sizes is relevant context when considering how much information each arm contributes, but it does not by itself explain the interval widths.

Intervals are more informative than point estimates alone because they show a range of compatible effects. They are not proof that every value in the range is equally likely, nor do they incorporate unreported design or analysis choices. The registry record does not report the confidence level, calculation method, missing-data assumptions, or a sponsor-reported inferential analysis for these primary contrasts. Accordingly, the stated endpoints should be interpreted as posted interval estimates with those methodological details unavailable.

The unadjusted p-values, 0.388 for 60 mg and 0.221 for 120 mg, complement but do not replace the intervals. Neither gives a measure of clinical importance, and neither addresses the broader set of outcomes or the possibility of selective interpretation across multiple comparisons.

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 expressed as participants per arm for 80% power and participants per arm for 90% power. These are planning illustrations based on the observed risk difference, not counts that were enrolled or observed. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

For each effect scenario, the 80% power column gives the estimated participants per arm for a design with an 80% chance of detecting that specified effect under the listed assumptions, if the assumptions hold. The 90% power column represents a higher target chance of detection and generally requires more participants per arm for the same scenario. Smaller effects require more participants because they are harder to distinguish from random variation. The planning display includes scenarios for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect.

All listed planning quantities for these binary outcomes are participants per arm; they are not total event counts. The general sample-size note distinguishes time-to-event calculations, which would report total events, from the other calculations, which report participants per arm. The curve is a visual companion to the planning scenarios and should be read as an illustration of how the assumed effect size relates to the required sample size, not as an additional observed result. These calculations are not observed power.

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 = 0.750; treatment proportion p₁ = 0.680; average p̄ = 0.715.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6383 = 1.2510.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6364 = 0.5356.
4. n = (1.2510 + 0.5356)² / (-0.0696)² = 659.1, rounded up to 660 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 <- 0.75                          # control proportion
p1 <- 0.680412371134021                          # 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(4003103)
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 = 660 (80% power), 882 (90% power)
 75% of observed effect: n per arm = 1,151 (80% power), 1,540 (90% power)
 50% of observed effect: n per arm = 2,539 (80% power), 3,399 (90% power)
power.prop.test: 659.1 
Simulated power at n = 660 per arm: 0.801 (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

The registry record identifies one primary endpoint and multiple secondary outcomes, but it does not report a statistical analysis plan describing how the family of outcomes was to be handled. No multiplicity adjustment is reported. The posted p-values for comparisons are unadjusted, so they do not account for testing multiple doses, outcomes, or time windows. In general, when many hypotheses are examined, the chance of at least one apparently unusual result can increase; adjustment or a prespecified testing hierarchy can address that issue, but neither is described in the registry record.

The record lists no reported analyses in its analysis listing. It therefore does not document a sponsor-reported model, covariate adjustment, hypothesis-testing sequence, interim analysis, or sensitivity analysis for the results discussed. Those elements are not reported in the registry record and should not be inferred from the posted summary counts or recalculated comparisons.

The primary analysis population is described as all participants who received at least one dose of study therapy. This is a treated-participant population and is not identified as an intention-to-treat population. The record does not report how many randomized participants received treatment, how participants were handled if they did not receive a dose, or whether the same population was used for each secondary outcome.

Missing-data procedures are not reported in the registry record. In particular, the record does not specify how incomplete Week 36 observation, withdrawal, or missing outcome assessments were handled. For a participant-count endpoint, incomplete follow-up could affect whether an event was observed during the stated timeframe. Without the corresponding rules and completeness information, the displayed counts cannot be used to infer a particular missing-data strategy.

These reporting gaps do not alter the arithmetic of the posted group summaries, but they limit reconstruction of the planned analysis and assessment of robustness. The unadjusted recalculations are useful descriptive contrasts; they should not be mistaken for a full protocol-based analysis whose choices and assumptions are documented in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intentional self-injury (1.0%), loss of consciousness (1.0%).

For serious adverse events through Week 24, the registry reports one participant in the 60 mg group, none in the 120 mg group, and none in the placebo group. The unadjusted risk-difference interval for 60 mg versus placebo runs from -0.010 to 0.030, with an estimate of 0.010. For 120 mg versus placebo, the estimate and interval are all 0.0 because no participants in either group were reported with a serious adverse event in this outcome.

These small counts offer limited information about comparative event frequency. In general, an absence of observed events in a study group is not proof that the underlying risk is zero, and an all-zero comparison cannot establish equivalence. The record also lists Intentional self-injury and Loss of consciousness among the top serious-event terms, each at 1.0%; the available summary does not specify their group attribution.

The adverse-event summary lists one death in the 60 mg group and none in the other groups. These are descriptive registry counts, and the record does not report a causal attribution for the death. Serious adverse-event counts, event terms, and deaths are distinct pieces of safety information and should not be treated as interchangeable outcomes.

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

The primary result describes the number of treated participants who had at least one recorded adverse event through Week 36 in each randomized group. The observed counts were 66.0 of 97.0 for 60 mg, 63.0 of 97.0 for 120 mg, and 36.0 of 48.0 for placebo. The unadjusted point estimates favor lower event proportions in the islatravir groups for this particular endpoint, but the intervals include zero and allow for uncertainty in either direction.

This result does not establish that one group has a different underlying safety profile, nor does it establish that the groups are equivalent. It does not show whether events were caused by study intervention, because the primary definition includes events whether or not they were considered related. It also does not summarize severity, recurrence, timing, or every category of adverse event. Separate outcomes are needed to address those questions.

The study was a Phase 2a trial in adults at low risk of HIV-1 infection, with monthly dosing described for 24 weeks and the primary event count followed through Week 36. The posted findings should be interpreted within that study population, regimen, and observation period. They should not be extended to other populations, dosing schedules, or follow-up periods that are not described in the registry record.

The registry does not report the original statistical plan, missing-data handling, multiplicity control, or sponsor-reported analyses for the posted comparisons. Thus the unadjusted calculations are informative descriptions of the posted group summaries, but they are not a substitute for a documented confirmatory analysis. The findings answer a narrow statistical question about observed event counts; they do not provide medical advice or a complete assessment of clinical benefit and risk.

17. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and follow-up periods are central to interpreting clinical safety results. The primary outcome counts participants with at least one adverse event, combining events whether or not they were considered related to intervention. Secondary outcomes divide safety into other categories, including drug-related events and serious events, and use a different timeframe. These are related but not interchangeable questions.

It also demonstrates the importance of distinguishing an observed point estimate from its precision. Both primary unadjusted intervals include zero, and the reported estimates therefore leave substantial uncertainty about the direction and size of the group differences. Counts alone can give an incomplete impression when arm sizes differ, so interval estimates and a clear comparison definition are needed for statistical interpretation.

The record provides group counts and outcome descriptions but no reported analysis listing, multiplicity plan, or missing-data procedures. This makes transparent separation of registry observations from recalculated comparisons especially important. It also shows why a planning illustration based on observed effects must not be confused with the assumptions used to design the original trial.

For clinical researchers and biostatisticians, the record is a practical example of reading a randomized study without treating unadjusted comparisons as a complete analysis. The most defensible reading combines the endpoint definition, event counts, intervals, population, and follow-up period, while keeping unreported design and analysis details explicitly unresolved.

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.

The registry record does not report detailed participant characteristics, eligibility criteria beyond the low-risk description, or the allocation procedure. As a result, the degree to which the enrolled sample represents other populations cannot be assessed from these results alone. The record identifies a randomized, double-blind, parallel design, but does not provide further detail about masking procedures or allocation concealment.

The primary analysis population is defined as participants who received at least one dose. The record does not give the corresponding analysis flow or specify how participants with incomplete follow-up were handled. Missing-data methods, outcome-assessment completeness, and sensitivity analyses are not reported. These omissions limit assessment of whether the observed counts could be affected by differences in follow-up or missing outcomes.

The posted inferential comparisons are unadjusted recalculations from summary counts. The registry does not report a sponsor analysis, a covariate-adjusted model, a multiplicity strategy, or the confidence-interval method. This makes it difficult to determine whether the displayed comparisons match the prespecified analysis, and the unadjusted secondary results require particular caution because multiple outcomes are listed.

The trial has relatively limited group sizes for rare outcomes, as reflected in the sparse serious-adverse-event counts. A lack of observed events in a group cannot establish that such events do not occur, and the registry summary does not supply enough detail to assess uncommon risks precisely. Finally, the dosing description covers 24 weeks while the primary adverse-event outcome extends through Week 36; the record does not provide detailed event timing or longer-term follow-up results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016) — NCT04003103.
• Registry record last updated 2025-07-18; status last verified 2025-07.
• Results first posted 2023-03-21.
• 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 NCT04003103, a completed Phase 2a randomized, double-blind, placebo-controlled, parallel-group study sponsored by Merck Sharp & Dohme LLC. It enrolled 242 adults at low risk of HIV-1 infection and evaluated once-monthly oral islatravir at 60 mg and 120 mg against placebo. Dosing was described for 24 weeks.

The primary outcome was the number of participants with at least one adverse event through Week 36, among participants who received at least one dose. The posted group counts were 66.0 of 97.0 for 60 mg, 63.0 of 97.0 for 120 mg, and 36.0 of 48.0 for placebo. Unadjusted risk-difference intervals for both dose comparisons include zero. Secondary outcomes include additional safety and pharmacokinetic measures, but the registry record does not report a complete analysis plan, multiplicity procedure, or missing-data approach.