Trial Outcomes & Findings for Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda (NCT NCT00405821)

Last Updated: 2012-09-28

Results Overview

Evaluate the effect of acyclovir prophylaxis vs placebo among HIV-1/HSV-2 co-infected individuals on the progression to AIDS (CD4+ less than 250 cells/microliter or World Health Org stage IV disease, excluding esophageal candidiasis)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

440 participants

Primary outcome timeframe

2 years

Results posted on

2012-09-28

Participant Flow

440 HIV+ subjects recruited in rural Rakai, Uganda within the Rakai Health Sciences Program mobile medical clinic during May 2007 thru November 2008

All subjects were randomized to study arm, and initiated study treatment at the time of enrollment.

Participant milestones

Participant milestones
Measure	Acyclovir 400mg Tablet Twice Daily	Placebo Tablet Twice Daily
Overall Study STARTED	220	220
Overall Study COMPLETED	198	198
Overall Study NOT COMPLETED	22	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Acyclovir 400mg Tablet Twice Daily	Placebo Tablet Twice Daily
Overall Study Death	5	7
Overall Study Lost to Follow-up	7	7
Overall Study Protocol Violation	1	0
Overall Study initiated ART	9	8

Baseline Characteristics

Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acyclovir 400mg Tablet Twice Daily n=220 Participants	Placebo Tablet Twice Daily n=220 Participants	Total n=440 Participants Total of all reporting groups
Age, Customized 20-29 years	46 participants n=5 Participants	44 participants n=7 Participants	90 participants n=5 Participants
Age, Customized 30-39 years	94 participants n=5 Participants	93 participants n=7 Participants	187 participants n=5 Participants
Age, Customized 40-49 years	54 participants n=5 Participants	53 participants n=7 Participants	107 participants n=5 Participants
Age, Customized 50+ years	26 participants n=5 Participants	30 participants n=7 Participants	56 participants n=5 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	161 Participants n=7 Participants	311 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	59 Participants n=7 Participants	129 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: Intention to treat analysis of all subjects randomized on the trial meeting the primary endpoint

Outcome measures

Outcome measures
Measure	Acyclovir 400mg Tablet Twice Daily n=220 Participants	Placebo Tablet Twice Daily n=220 Participants
Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)	95 participants	110 participants

SECONDARY outcome

Timeframe: 2 years

Population: We conducted monthly clinical assessment for GUD on all randomized subjects during their entire follow-up period on this trial. The number of episodes of GUD is shown below.

We calculated incidence rate for each treatment arm for episodes of genital ulcer disease, and incidence rate ratio.

Outcome measures

Outcome measures
Measure	Acyclovir 400mg Tablet Twice Daily n=220 Participants	Placebo Tablet Twice Daily n=220 Participants
Difference in Number of Episodes of Genital Ulcer Disease Between Arms	27 episodes	47 episodes

SECONDARY outcome

Timeframe: baseline, 6 months, 12 months, 18 months, 24 months

Population: We measured viral load at baseline and at 6 monthly follow-up visits during 24 months of follow-up for all subjects randomized on this study.

We measured mean annual rate of change in log10 viral load (copies/mL) for each group. We assessed difference in annual rate of change in log10 viral load (copies/mL) between groups.

Outcome measures

Outcome measures
Measure	Acyclovir 400mg Tablet Twice Daily n=220 Participants	Placebo Tablet Twice Daily n=220 Participants
HIV-1 Viral Load Difference Between Arms	-0.061 log10 (copies/mL) Interval -0.25 to 0.129	0.402 log10 (copies/mL) Interval 0.212 to 0.592

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months and 12 moths post ART initiation

Outcome measures

Outcome data not reported

Adverse Events

Acyclovir 400mg Tablet Twice Daily

Serious events: 75 serious events

Other events: 219 other events

Deaths: 0 deaths

Placebo Tablet Twice Daily

Serious events: 85 serious events

Other events: 218 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Steven Reynolds

NIAID

Phone: 256-772-220-087

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Acyclovir 400mg Tablet Twice Daily n=220 participants at risk	Placebo Tablet Twice Daily n=220 participants at risk
Infections and infestations TB Adenitis	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Malaria	11.8% 26/220 • Number of events 29 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	10.9% 24/220 • Number of events 34 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Mastitis	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Blood and lymphatic system disorders Anemia	3.2% 7/220 • Number of events 9 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	5.9% 13/220 • Number of events 16 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
General disorders Dehydration	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
General disorders Febrile Illness, unspecified	2.3% 5/220 • Number of events 5 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	2.3% 5/220 • Number of events 6 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations skin infection, unspecified	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders wound, unspecified	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations EENT infection, unspecified	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Vascular disorders Hypertension	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Bacterial pneumonia	1.4% 3/220 • Number of events 3 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Pulmonary Tuberculosis	5.9% 13/220 • Number of events 13 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	5.9% 13/220 • Number of events 14 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Extra-pulmonary tuberculosis	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Upper respiratory tract infection	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Lower respiratory tract infection	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory complaint, unspecified	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.45% 1/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Cryptococcal meningitis	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Esophageal candidiasis	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Peptic ulcer disease	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Gastroenteritis	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Cholecystitis	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Hepatotoxicity	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Abdominal pain, unspecified	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	1.4% 3/220 • Number of events 3 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Injury, poisoning and procedural complications Trauma to chest	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Reproductive system and breast disorders Pelvic inflammatory disease	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Genito-urinary disease (GUD)	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Cystitis	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Urinary Tract Infection	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.00% 0/220 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Pregnancy, puerperium and perinatal conditions Abortion	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Pregnancy, puerperium and perinatal conditions Pregnancy	13.6% 30/220 • Number of events 37 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	18.6% 41/220 • Number of events 52 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Pregnancy, puerperium and perinatal conditions Pregnancy complication, unspecified	2.3% 5/220 • Number of events 5 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kaposi's sarcoma	0.45% 1/220 • Number of events 1 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	0.91% 2/220 • Number of events 2 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.

Measure	Acyclovir 400mg Tablet Twice Daily n=220 participants at risk	Placebo Tablet Twice Daily n=220 participants at risk
Infections and infestations Malaria	48.6% 107/220 • Number of events 211 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	47.7% 105/220 • Number of events 204 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
General disorders Lymphadenopathy	11.4% 25/220 • Number of events 30 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	16.4% 36/220 • Number of events 47 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
General disorders Decreased appetite	13.6% 30/220 • Number of events 35 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	13.2% 29/220 • Number of events 33 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
General disorders General complaint, unspecified	52.3% 115/220 • Number of events 217 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	55.9% 123/220 • Number of events 252 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders Herpes zoster	1.8% 4/220 • Number of events 4 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	8.2% 18/220 • Number of events 18 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations fungal skin infection	29.1% 64/220 • Number of events 102 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	20.9% 46/220 • Number of events 70 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations angular chelitis	9.5% 21/220 • Number of events 23 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	15.5% 34/220 • Number of events 45 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders Papulo-pruritic eruption (PPE)	6.8% 15/220 • Number of events 21 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	10.0% 22/220 • Number of events 27 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders Darkening nails	14.1% 31/220 • Number of events 32 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	14.5% 32/220 • Number of events 32 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders Rash, unspecified	53.6% 118/220 • Number of events 227 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	54.1% 119/220 • Number of events 201 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Skin and subcutaneous tissue disorders Skin complaint, unspecified	55.9% 123/220 • Number of events 213 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	55.5% 122/220 • Number of events 212 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Rhinitis	9.1% 20/220 • Number of events 20 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	8.2% 18/220 • Number of events 20 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Conjunctivitis	13.2% 29/220 • Number of events 34 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	14.5% 32/220 • Number of events 40 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Eye disorders Allergic conjunctivitis	15.0% 33/220 • Number of events 41 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	9.5% 21/220 • Number of events 29 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Ear and labyrinth disorders Hearing Loss	6.4% 14/220 • Number of events 16 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	6.8% 15/220 • Number of events 16 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Cardiac disorders Palpitations	14.5% 32/220 • Number of events 41 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	18.6% 41/220 • Number of events 58 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Upper respiratory tract infection	96.4% 212/220 • Number of events 1242 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	96.4% 212/220 • Number of events 1226 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory complaint, unspecified	44.5% 98/220 • Number of events 152 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	37.3% 82/220 • Number of events 132 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Nervous system disorders HIV neuritis	16.4% 36/220 • Number of events 45 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	10.0% 22/220 • Number of events 24 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Nervous system disorders post-herpetic neuralgia	3.2% 7/220 • Number of events 8 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	6.8% 15/220 • Number of events 20 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Nervous system disorders Nervous system, other complaint	25.0% 55/220 • Number of events 76 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	20.9% 46/220 • Number of events 68 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Oral candidiasis	6.8% 15/220 • Number of events 26 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	10.5% 23/220 • Number of events 40 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Peptic ulcer disease	28.6% 63/220 • Number of events 124 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	27.3% 60/220 • Number of events 115 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Intestinal helminthiasis	5.5% 12/220 • Number of events 12 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	9.1% 20/220 • Number of events 25 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Gastroenteritis	18.6% 41/220 • Number of events 55 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	15.0% 33/220 • Number of events 55 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Gastritis	12.3% 27/220 • Number of events 31 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	15.0% 33/220 • Number of events 42 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Gastrointestinal disorders Gastrointestinal, other complaint	76.4% 168/220 • Number of events 415 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	71.4% 157/220 • Number of events 488 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Musculoskeletal and connective tissue disorders Arthritis	8.6% 19/220 • Number of events 23 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	6.8% 15/220 • Number of events 18 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Injury, poisoning and procedural complications Traumatic injury	7.3% 16/220 • Number of events 18 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	7.3% 16/220 • Number of events 16 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Musculoskeletal and connective tissue disorders Musculoskeletal joint pain, unspecified	75.0% 165/220 • Number of events 470 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	73.6% 162/220 • Number of events 472 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Reproductive system and breast disorders Pelvic inflammatory disease	9.5% 21/220 • Number of events 22 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	9.5% 21/220 • Number of events 24 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Gonorrhea	6.4% 14/220 • Number of events 20 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	5.5% 12/220 • Number of events 14 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Genito-urinary disease (GUD)	17.7% 39/220 • Number of events 52 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	35.0% 77/220 • Number of events 131 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Vaginal candidiasis	36.4% 80/220 • Number of events 134 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	35.9% 79/220 • Number of events 159 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Infections and infestations Urinary Tract Infection	16.4% 36/220 • Number of events 48 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	17.7% 39/220 • Number of events 55 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Reproductive system and breast disorders Vaginal discharge	4.5% 10/220 • Number of events 10 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	6.4% 14/220 • Number of events 16 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.
Reproductive system and breast disorders Genitourinary, other complaint	59.5% 131/220 • Number of events 280 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.	63.6% 140/220 • Number of events 356 • maximum follow-up time on this study ranged from 24 months to 41 months depending on time of enrollment.