HIV, CONTRACEPTION AND ASSISTED REPRODUCTIVE

TECHNOLOGY

PERSEPECTIVES FROM A DEVELOPING COUNTRY (KENYA)

Elizabeth Bukusi

OVERVIEW

Contraceptive use among HIV positive women in a cohort in Nairobi

Hormonal contraceptive use and their effects among a sex worker cohort in Mombasa

Assisted reproduction technology- a needs perspective from Kenya

Kenyan Research Sites

Characteristics of a cohort of HIV infected women on steroid and

non-steroid hormone contraception

Mwachari C1, Omondi C 1, Kariuki J1, Thiongo L1, Cohen CR2*

1. Kenya Medical Research Institute, Nairobi2. University of Washington, Seattle,*

Current affiliation University of San Francisco, California

BACKGROUND

Dec 2002 UNAIDS/WHO estimated 19.2M women were infected with HIV worldwide

The majority of these women in the reproductive age hence need for reliable contraception

Many women use steroid hormones for contraception

Steroid hormones may interact with HIV virus or alter the immune function through various mechanisms

CONT…BACKGROUND

Identified a need to study the effects of hormonal contraception on HIV progression

METHODS Study sites: Nairobi, Kenya and Harare, Zimbabwe, Chula,

Thailand.

Study Design: Prospective non-randomized cohort study

Subjects assigned to contraceptive group (current contraceptive method of their choice at least 3 months prior to enrollment)

METHODS (cont..) Subject population:

18-35 years documented HIV infection CD4 count ≥ 500 cells/ul At least 3 months of contraception Nairobi resident

Follow up every 3 months for 4 years

CLINICAL PROCEDURES

Obtain study and HIV consent Medical, behavioral, contraception history Medical examination

Laboratory Procedures At Enrollment - FBC, RPR, plasma viral load, CD4/CD8

- pap smear- CVL

Every 6 months - FBC, CD4/CD8, plasma viral load

Every 12 months - pap smear- CVL- RPR

RESULTS 5,188 WOMEN SCREENED

25.8% HIV SEROPREVALENCE

227(4.5%) HIV-1 INFECTED WOMEN ENROLLED

175 (77%) ON STEROID HORMONE CONTRACEPTIVES AND 52 (23%) ON NON-STEROID HORMONE CONTRACEPTIVES

75% FOLLOW-UP AFTER ONE YEAR

Steroid hormone contraceptives

0%

10%

20%

30%

40%

50%

60%

70%

Type ofcontraception

Depo

OCS

Norplant

Table 1: Socio-demographic profile of cohortCHARACTERISTIC HORMONAL

N=175

NON-HORMONAL N=52

P-VALUE

AGE <30 YRS

162 (92.6%) 32 (61.5%) P<0.01

MARRIED WIDOWED

SINGLE

160 (91.4%)

12 (6.9%)

3 (1.7%)

34 (65.4%)

14 (26.9%)

4 (7.7%)

P<0.01

SES LOW SES HIGH

138 (78.9%)

37 (21.1%)

31(59.6%)

21 (40.4%)

P<0.01

Ever Alcohol Use YES 33 (18.9%) 25 (51.9%) P<0.01

Ever Smoked YES 6 (3.4%) 6 (11.6%) P=0.05

Breastfeeding YES 81 (46.8%) 7 (13.5%) p<0.01

Cont…Table 1: Socio-demographic profile of cohort

CHARACTERISTIC HORMONAL

USERS

N=149

NON HORMONAL USERS

N=30

SIGNIFANCE

CONDOM USE IN LAST ONE MONTH

Never/less than half the time

More than half the time

Always

136 (91.3%)

6 (4.0%)

7 (4.7%)

13 (43.3%)

3 (10.0%)

14 (46.7%) P <0.01

n=174 n=52

NUMBER OF SEXUAL PARTNERS EVER HAD

1 partner

2-3 partners

4+ partners

26 (14.9%)

97 (55.7%)

51(29.3%)

6 (11.5%)

21 (40.4%)

25 (49.1%) P<0.03

Fig 1: Median Rate of CD4 decline over 12 months

y = -57x + 708.33

y = -43x + 765.33

0100200

300400500600

700800

Adm 6 mths 12 mths

Period

Me

dia

n C

D4

de

clin

e

Hormonal Non-Hormonal

Linear (Non-Hormonal) Linear (Hormonal)

SUMMARY HIV + women using steroid hormone contraceptives

tended to be younger, married, lower SES, and likely to be breastfeeding at one year.

There was significantly lower condom use among hormonal contraceptive users than that of non-hormonal contraceptive users.

SUMMARY In this cohort steroid hormonal users tended

to have higher median CD4 counts, lower at one year.

Median rate of CD4 decline over one year was not significant between steroid hormonal users Vs non-steroid hormonal users

Acknowledgements

Dr. Craig Cohen, Dr. Abuaba, Kariuki J, Lucy S, Lilian M, Jabuya E, Miheso B, Lawrence T, Jane M, Scola M, Jarmen K, Henry K

Study participants KEMRI

Hormonal contraception and Hormonal contraception and sexually transmitted infections / sexually transmitted infections / HIV-1 infection in womenHIV-1 infection in women

Ludo LavreysUniversity of Washington, Seattle, USAUniversity of Nairobi, Nairobi, Kenya

Annual Review Meeting UoN STD/AIDS Collaborative Group

Holiday Inn Mayfair Hotel, Nairobi, 2 February 2005

Contraceptive use inMombasa Cohort and in Kenya

Cohorta Kenya – 2003a,b

Oral contraceptive pillsDepot medroxyprogesterone

acetate (DMPA - Depo)Norplant

CondomsIUDFemale sterilizationDiaphragm

12.3%22.2%

1.9%

10.6%1.9%2.4%0.0%

7.2%13.8%

1.6%

1.2%2.4%4.3%

?

a % married: cohort: 1.5%; National survey: 100%b Kenya Demographic and Health Survey 2003 Preliminary Report

Hormonal contraception and sexually transmitted infections

Does the use of hormonal contraception increase a woman’s risk for cervical sexually transmitted infections?

HCC use and cervical STIs among HIV-1 negative sex workers in Mombasa

Baeten J, et al. Am J Obstet Gynecol 2001; 185:380-385.

OCP DMPA

HR (95% CI) P HR (95% CI) P

C. trachomatis 1.8 (1.1-2.9) .03 1.6 (1.1-2.4) .02

N. gonorrhoeae 1.4 (0.9-2.1) .1 1.1 (0.8-1.6) .5

Cervicitis 1.8 (1.5-2.2) < .001 1.5 (1.2-1.9) .001

Adjusted for age, yrs of education, yrs of prostitution, parity, workplace, number of sexual partners per week, numbers of sex encounters per week, and condom use

Hormonal contraceptive use and cervical STIs among HIV-1 positive sex workers in Mombasa

Incidence per 100 PY of FU

(N cases)

OCP DMPA

HR (95% CI) P HR (95% CI) P

C. trachomatis 7.7 (26) 2.2 (0.7-7.3) .2 3.1 (1.0-9.4) .05

N. gonorrhoeae

14.9 (119) 0.6 (0.3-1.3) .2 1.0 (0.6-1.7) .9

Cervicitis 24.2 (193) 2.3 (1.4-3.8) .001 1.6 (1.0-2.3) .03

Adjusted for age, yrs of education, yrs of prostitution, parity, workplace, number of sexual partners per week, and condom use

Lavreys L , et al. AIDS 2004;18:2179-84.

Summary (1)

The use of hormonal contraception is associated with increased risk for:

Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness

Hormonal contraception and HIV-1 acquisition

Does the use of hormonal contraception increase a woman’s risk for HIV-1 acquisition?

Hormonal contraception and risk of HIV-1 acquisition

Period 1993-19971

(N=779)

HR 95% CI

p

None/Tubal ligation

1.0

DMPA 2.0 1.3-.1 .003

Oral contraceptives

1.3 0.8-2.2

.3

Adjusting for sexual behavior, condom use, and sexually transmitted infections

1Martin HM, et al. J Infect Dis 1998;178:1053-1059.

Hormonal contraception and risk of HIV-1 acquisition

Period 1993-19971

(N=779)

Period 1993-20032

(N=1272)

HR 95% CI

p HR 95% CI

p

None/Tubal ligation

1.0 1.0

DMPA 2.0 1.3-3.1

.003 1.8 1.4-2.4 <.001

Oral contraceptives

1.3 0.8-2.2

.3 1.5 1.0-2.1 .04

Adjusting for sexual behavior, condom use, and sexually transmitted infections

1Martin HM, et al. J Infect Dis 1998;178:1053-1059.

2Lavreys L, et al. AIDS 2004;18:695-697.

Summary (2)

The use of hormonal contraception is associated with increased risk for:

Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness

HIV-1 acquisition

Hormonal contraception and natural history of HIV-1

Does the use of hormonal contraception affect the natural history of HIV-1 infection?

3.5

4

4.5

5

5.5

6

6.5

7

0 12 24 36 48 60 72 84 96

Time since infection (months)

Vir

al l

oa

d (

log

co

pie

s/m

l)DMPA

NO DMPA

DMPA

Lavreys L, et al. J Infect Dis 2004;189:303-311.

Viral diversity and use of DMPA

Multiple viral variants detected in 89/156 women (57%)

HIV-1 viral diversity during primary infection was associated with use of DMPA at the time of HIV-1 acquisition (OR 3.0, 95% CI 1.3-6.9, p=0.005)

Sagar M, et al. AIDS 2004;18:615-619.

Summary (3)

The use of hormonal contraception is associated with increased risk for:

Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness

HIV-1 acquisition

Higher viral load at set point, which might lead to faster disease progression

Acquisition of a more complex viral population, leading to a higher plasma viral load, and faster decline in CD4 count

Hormonal contraception and HIV-1 infectiousness

Does the use of hormonal contraception affect shedding of HIV-1 in the female genital tract, and hence the risk of transmitting HIV-1 infection?

Hormonal contraception and HIV-1 infectiousness

Mostad, et al. Lancet 1997;350:922-927

Adj

ust

ed o

dds

ratio

Cross-sectional

N=308

Hormonal contraception and HIV-1 infectiousness

Wang et al. AIDS 2004;18:205-209

Adj

ust

ed o

dds

ratio Cervical HIV-1 DNA prevalence (n=211)

Cross-sectional Prospective

Before HC After HC OR (95% CI) P

42% 52% 1.62 (1.03-2.63) 0.03

N=308

Mostad, et al. Lancet 1997;350:922-927

Summary (4)

The use of hormonal contraception is associated with increased risk for:

Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness

HIV-1 acquisition

Higher viral load at set point, which might lead to faster disease progression

Acquisition of a more complex viral population, leading to a higher plasma viral load, and faster decline in CD4 count

Shedding of virus in the genital tract of HIV-1 infected women, which might lead to increased infectiousness

Recommendations?

Ref: Network Vol 23, number 3, 2004. Family Health International

Recommendations?

Ref: Network Vol 23, number 3, 2004. Family Health International

Our Collaborators

Mombasa:

Bhavna Chohan**Varsha ChohanWisal HassanChristine Katingima Kishor MandaliyaScott McClellandClinic and lab staffAll patients

Nairobi (UoN) :Walter JaokoJeckoniah Ndinya-Achola

Seattle (UW and FHCRC):Jared Baeten*Julie OverbaughDana PanteleeffBarbra RichardsonManish SagarIARTP staff

* Current affiliation: Massachusetts General Hospital, Boston * *Current affiliation: Fred Hutchinson Cancer Research Center, Seattle

High Acceptability Of Hiv-1 Testing Among Infertile Couples Attending A Refferal Infertility

Clinic In Nairobi, Kenya

Bukusi E1,2, Sinei S2, Cohen C 2,3

1Kenya Medical Research Institute2University of Nairobi,3University of Washington

Women and Men combined

36/40 (90%)

Couples 17/20(85%)

Women only 19/20(95%)

Men only 17/20(85%)

ACCEPTANCE OF HIV TESTING AMONG INFERTILE COUPLES

HIV-1 concordant negative couples

13/17 (76%)

HIV-1 concordant positive couples

1/17(6%)

HIV-1 discordant couples

3/17 (18%)

Discordant couple male HIV-1 positive

1/3 (33%)

Discordant couple female HIV -1 positive

2/3(66%)

HIV-1 serostatus among Infertile couples

Phase III Randomized Placebo-Controlled Trial of HSV-2 Suppression to Prevent HIV Transmission

among HIV-Discordant Couples

Dr. Craig Cohen1, Dr. Elizabeth Bukusi2, Dr. Videlis Nduba2, Dr. Anjali Sharma2, Dr. Kawango Agot3

1University of California, San Francisco, 2Kenya Medical Research Institute,3University of Nairobi, University of Manitoba and

University of Illinois

Kisumu CIS Discordant couple data*

Positive Partner Number

Total 101

Female 71

Male 30

*Jan 2005, VCT sites