Inclusion Criteria:
1. Males or females at least 18 years of age.
2. Tested positive for HIV by either blood antigen/antibody combination HIV-1/2 immunoassay, HIV-1/HIV-2 antibody differentiation immunoassay, or nucleic acid tests (e.g., HIV ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]). Participants who are newly diagnosed with HIV infection by an antigen/antibody combination HIV-1/2 immunoassay are allowed to be included in the study, but the infection should be subsequently confirmed by an HIV-1/HIV-2 antibody differentiation immunoassay or nucleic acid tests.
3. Diagnosed with definitive, presumptive, or clinically suspected PCP prior to randomisation.
4. Willing and able to provide written informed consent. If the participant is unable to provide consent, a legally acceptable representative (i.e., acceptable to ICH and local law, as applicable) must provide informed consent on the participant's behalf.
5. Participants of childbearing potential (all biologically female participants between 18 years and \<2 years post-menopausal unless surgically sterile) must agree to use a highly effective contraceptive measure during the study period (from enrolment) and for at least 30 days after the last dose of rezafungin.
6. Biologically male participants who are not vasectomised must agree to the following requirements during the study period (from enrolment) and for at least 120 days after the last dose of rezafungin:
* Refrain from donating sperm PLUS, either
* Abstain from sexual intercourse with a female of childbearing potential as their preferred and usual lifestyle OR
* Use barrier contraception (i.e., male condom with or without spermicide) when having sexual intercourse with a female of childbearing potential who is not currently pregnant.
Exclusion Criteria:
1. Under 18 years of age.
2. Known or suspected hypersensitivity or allergic reaction to co-trimoxazole, rezafungin, any echinocandin, or any component of these formulations, including, but not limited to, anaphylaxis or exfoliative skin disorders (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis).
3. Any contraindication to co-trimoxazole or intake of a medication or supplement known to severely interact with co-trimoxazole as detailed in the Summary of Product Characteristics (SmPC) of co-trimoxazole, including, but not limited to, acute porphyria or a history of drug-induced immune thrombocytopaenia with use of trimethoprim and/or sulphonamides.
4. Creatinine clearance \<15 mL/min or receiving renal replacement therapy.
5. Severe hepatic impairment, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 × upper limits of normal (ULN), or total bilirubin \>3 × ULN, or a history of chronic cirrhosis (Child-Pugh score \>9).
6. A neutrophil count \<1,000 cells/µL or a platelet count \<50,000 cells/µL.
7. Immunosuppressive disease other than HIV / acquired immunodeficiency syndrome (AIDS) (e.g., haematopoietic stem cell transplant, solid organ transplant, or primary immune deficiencies) OR prolonged use of immune-weakening medications:
* Having received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry, or
* Having received biologics (e.g., infliximab, ustekinumab), immunomodulators (e.g., methotrexate, mercaptopurine, azathioprine), or cancer chemotherapy within 90 days prior to study entry.
8. Previously diagnosed with PCP and having received treatment in the past 6 weeks.
9. Receiving therapy for PCP at approved therapeutic doses for \>48 hours before randomisation. Exception: receipt of an anti-PCP drug at prophylactic doses (i.e., lower than approved therapeutic doses).
10. Meeting National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 criteria for ataxia, tremors, motor neuropathy, or sensory neuropathy of Grade 2 or higher.
11. History of severe ataxia, tremors, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease and Huntington's disease).
12. Planned or ongoing therapy at Screening with a known severe neurotoxic medication or with a known moderate neurotoxic medication in a participant with ataxia, tremors, motor neuropathy, or sensory neuropathy of NCI-CTCAE version 5.0 Grade 1 or higher.
13. Previous participation in this or any other rezafungin study.
14. Female participants who are pregnant or lactating.
15. Having a concomitant disease or any medical condition (including other HIV-associated infection or complication) that, in the opinion of the Investigator, could pose undue risk to the participant, impede completion of the study procedures (e.g., patients who are not expected to survive even with treatment), or would compromise the validity of the study measurements.
16. Receipt of an investigational drug within 30 days prior to dosing of the study drug(s), presence of an investigational device at the time of Screening, or is planning to participate in another interventional clinical study while enrolled in this study.
17. The Investigator is of the opinion the participant should not participate in the study.
Late Exclusion Criteria:
The diagnosis of PCP will be reviewed by the Investigator on Day 8 (before dosing the study drug). Participants will be withdrawn from the study if any of the following criteria apply (i.e., participants without a diagnosis of definitive or presumptive PCP on Day 8):
1. Lack of positive P. jirovecii immunofluorescence or PCR of bronchoalveolar lavage, endotracheal aspirates, bronchoscopic tissue biopsy, or induced sputum AND serum β-D-glucan below the positive cut-off value.
2. Serum β-D-glucan below the positive cut-off value in participants in whom collection of a suitable respiratory sample is not possible.
3. Radiographic features on chest CT performed after randomisation not consistent with PCP after taking into account the clinical and microbiological findings.
