1. HIV/Sexually Transmitted Disease Interactions
A Biomedical Approach to HIV Prevention
Good morning.
Our topic for this hour is the interactions between HIV and sexually transmitted diseases, how these interactions affect HIV transmission, and what can be done about it.
I’m Linda Creegan, I’m a family nurse practitioner, and I’ve worked for the past 11 years or so at City Clinic, which is the STD clinic in San Francisco. I also teach as a faculty member for the California HIV/STD Prevention Training Center, and I’m very happy to be here this morning.
California STD/HIV Prevention Training Center
Berkeley, CA

2. HIV/STD Connections Introduction
Similar behaviors transmit HIV and STDS
Vaginal and anal intercourse
Injection drug use with shared needles or equipment
Potential interactions between HIV and STDs are multiple and complex
There are several important points of connection that we will be discussing.
I’m leaving out the maternal/child transmission issues today; and concentrating on issues related to sexual transmission.
Most basically, we know that similar sexual and drug-use behaviors can transmit both STDs and HIV. But in addition to the actual behaviors, other factors that we’ll discuss come into play. It’s important to acknowledge upfront that the potential interactions between HIV and STDs are in fact multiple and complex.

3. The STD Cofactor Presentation Overview
Sexual transmission of HIV
Impact of STDs on the sexual transmission of HIV
HIV prevention through STD control
So today we’ll examine what’s known about the
sexual transmission of HIV,
the impact of STDs on the sexual transmission of HIV
and how STD control may help prevent new cases of HIV.

4. Approaches to HIV Prevention
Behavior change
Biomedical intervention

5. Sexual Transmission of HIV
Accounts for 75-85% of HIV infections worldwide
Heterosexual transmission is the major cause in developing nations, and is the most rapidly increasing subset of US AIDS cases
Homosexual transmission continues among MSM in developed countries
It’s thought that today sexual transmission accounts for most HIV transmission worldwide, in the US as well as in other countries.
Both heterosexual and homosexual transmission are important contributors.
Royce et al, NEJM 97

6. Sexual Transmission of HIV Risks of Different Behaviors
Risk of transmission is low after a single sexual contact
Receptive anal intercourse: %
Penile-vaginal intercourse:
M to F = %, F to M = %
Oral intercourse: unclear, but ~ 10x lower than vaginal intercourse
Cofactors important in transmission:
STDs are one such co-factor
But many people are surprised to hear how low the per-exposure risk of contracting HIV is, that is, how likely am I to catch HIV from a single sexual contact with an HIV-positive partner?
The best estimates are that the riskiest exposures, that is receptive anal intercourse, carries a per-exposure risk of around 1-3%.
The risk of HIV transmission from vaginal intercourse is considerably lower, less than 1%.
And oral sex carries a much lower risk, so low in fact that the per-contact risk is difficult to calculate from available data.
So why is HIV spreading? Surely cofactors are important in transmission, and STDs are known to be one such cofactor.

7. STDs and HIV: Possible Interactions
Transmission
Infectiousness
Susceptibility
Alteration of disease natural history
HIV
STDs
There are several ways in which STDs and HIV can potentially interact.
The first is around transmission.
STDs may make HIV more or less easy to transmit, and HIV may make STDs more or less easy to transmit.
We’ll concentrate today on what is known about STDs making HIV more easy to transmit, because this is where most of the research is done.And that’s logical because we’re most interested in trying to get a handle on how STD control might help prevent HIV transmission.
Transmission can be thought of as a two-way street, and either direction of traffic can be affected.
Infectiousness of HIV may be increased, that is, there may be an increased transmission probability when the HIV-positive partner in a relationship has an STD.
And Susceptibility to HIV may be increased, that is, there may be an increased probability of transmission when the HIV-negative partner within a relationship has an STD.
And we need to consider whether there of interactions between STDs and HIV that may make either type of disease more or less serious. Perhaps someone with an STD and HIV at the same time has more trouble controlling symptoms of the STDS, or responding to treatment. Or perhaps in people co-infected with HIV and STDS, the HIV progresses more rapidly.

8. Epidemiologic Triangle
HOST
Now, I promise not to bore you with too much theory (I’m bored by it myself!) but this little diagram helps us visualize what other factors and cofactors come into play besides sexual behavior alone.
The classic way to look at the transmission of any communicable disease, be it Tuberculosis or SARS or HIV, is to consider the human host, the agent or germ itself (HIV, STDs), and the environment in which the disease is spreading.
Let’s look at each of these as they relate to HIV and STDs individually for a moment.
We’ll look at host factors last, because we’re going to spend the most time there.
AGENT
ENVIRONMENT

9. Agent Factors HIV viral subtypes
Cellular attraction(affinity, tropism) to virus
Target cells = CD4, Langerhans, macrophages
Phenotypic differences between blood and seminal isolates
Our agent in this case is the HIV virus.
There are several viral subtypes, some of which may be more virulent or aggressive than other.
The virus must gain access to certain human cells, primarily those with the CD4 receptor on the cell membrane.
And the virus may look and act somewhat differently in different body compartments and fluids. For instance, HIV may act somewhat differently in blood than in semen. I never stop being amazed at what a tricky bastard HIV is.
NEJM 97

10. Environmental Factors
Social, cultural & political milieu affecting:
Sexual practices
Patterns of partnering
Commercial sex
Gender relations
Contraceptive choice
Substance abuse
Education
Economic resources
Environmental factors include many, many variables. A couple of examples of environmental factors affecting HIV transmission would be condom use and availability of clean needles for people who inject drugs.
Really anything not intrinsic to the biology of the person, or the biology of the bug would be considered environmental.
NEJM 97

11. Host Factors - Infectiousness
Genital reservoirs of HIV
Female: cervical zone of transformation
Male: seminal cells and seminal plasma, foreskin
Blood (serum) viral load
Level of virus in secretions
Now we’ll consider in detail the host factors. What kinds of factors might make an HIV-positive individual more or less likely to pass HIV on? This is called infectiousness.
We’re familiar with the blood test that measures viral load, but this of course is SERUM or BLOOD viral load, and HIV does appear and can be measured in other fluids, including vaginal fluid and semen. And the viral load in these fluids can be different, higher or lower, than the viral load in the blood.
It stands to reason that with more virus around, in this instance higher viral load in the semen, would make a person more infectious.
NEJM 97

12. Factors Increasing Host Infectiousness
Recent HIV infection
Late stage HIV infection
Menstruation
Non-circumcision (intact foreskin)
Lack of antiretrovirals (?)
STDs (ulcerative, inflammatory)
Other factors thought to increase infectiousness include recent and late-stage HIV infection, when serum viral load is known to be higher, menstruation, and non-circumcision in men.
Antiretrovirals I consider an environmental factor but it does look like effective viral suppression with antiretrovirals decreases a person’s infectiousness, not 100% but considerably.
And good evidence from multiple studies show that STDs increase infectiousness.
NEJM 97

13. Host Factors - Susceptibility
Target cells = CD4, Langerhans, macrophages
Found in oral, cervicovaginal, foreskin, urethral and rectal epithelium
Inflammation in any of these sites may increase number or receptivity of target cells
Anatomical factors (circumcision, ectopy)
Genetic factors (CCR5)
What variables help make an HIV-negative individual more susceptible to infection?
First, the number and location of HIV’s target cells, the CD4 + cells. These are found in many tissues that are exposed during sex, including oral, genital and anal tissues. The foreskin in particular seems to be susceptible tissue because of the presence of CD4-bearing cells called Langerhans cells in the foreskin.
And there seems to be some mechanism of genetic protection in certain persons, involving a immune factor called CKR5. This fact you’re probably familiar with, both from the reports showing that some people seem not to catch HIV, despite multiple exposures, and from the studies of “long-term non-progressors” who become infected with HIV but do not lose immune function. It’s not fully understood how this immune factor protects those who have it.
(Chemokine receptor CKR5 important for infection; Mutation in CKR5 found to be protective; homozygosity = resistance to infection heterozygosity = slowed progression of disease; Frequency of mutation varies among different populations; Higher in white c/w blacks)
NEJM 97

14. Factors Increasing Host Susceptibility
Non-circumcision (intact foreskin)
Trauma
STDs (ulcerative> inflammatory)
Menstruation
Cervical ectopy
Other genital infections ?
So what can increase a person’s susceptibility to HIV infection?
Well, we’ve already talked about the connection of the foreskin rich in Langerhans cells, and studies bear out the finding that non-circumcised males are more likely to become HIV-infected.
Trauma, the presence of menstrual blood,and a normal condition of the cervix called ectopy also increase susceptibility.
And finally again, STDs and perhaps other genital infections and conditions can increase susceptibility.
NEJM 97

15. The Impact of STDs on Sexual Transmission of HIV
STDs increase susceptibility to and infectiousness of HIV infection
Risk of HIV transmission is 2 to 5 times higher in the presence of other STDs
SO……….
STD control can be an effective intervention in reducing HIV transmission
Because STDs impact both the infectivity and susceptibility to HIV, the risk of HIV transmission is generally 2 to 5 times higher in the presence of another STD. We’ll look more carefully at the research evidence that supports this in just a moment.
But given this fact,…. it stands to reason that preventing and controlling STDs could be an effective way to reduce HIV transmission in a population.

16. The Impact of STDs on Sexual Transmission of HIV
Types of evidence
Studies on the biological plausibility and potential pathogenic mechanisms
Cohort studies of HIV seroconversion associated with specific STDs
Community level interventions assessing the impact of STD treatment on HIV incidence
What research findings do we have to support these ideas, both that STDs are a cofactor in transmission and that controlling STDs might cut down on HIV transmission?
Well there are studies that look at the biological mechanisms behind HOW STDs might increase HIV transmission. What’s different about the body when an STD is present that makes transmission more likely?
And there are studies that look at groups of people to see if co-infection with STDs are associated with more HIV transmission. These are the so-called “prospective cohort studies”, in which a group of people is followed over time to see whether some with certain variables present (like STDs) are more or less likely to catch HIV.
And there are studies that attempt to demonstrate lower HIV transmission when STDs are prevented or controlled.
Let’s look at all three types of studies.

17. Biological Mechanisms for the STD Cofactor
Infectiousness:
Inflammation increases HIV viral load in genital secretions
HIV can be cultured from genital lesions such as ulcers of syphilis
Susceptibility:
Breaks in epithelial barrier allow viral access
Inflammation increases number and/or receptivity of target cells
Enhancement of viral survival
We know that inflammation increases the amount of HIV found in genital secretions like semen and vaginal fluid. Inflammation is the body’s basic way of fighting off infection. Essentially, when the body recognizes an invader like an bacterium or a virus, The blood flow to that area increases carrying in various “soldiers” to fight the infection. These soldiers include white blood cells and lots of immune chemicals to contain and kill the invader. This process results in the familiar signs of inflammation: redness, heat, swelling pain and in some instances, pus. Pus is composed of 90% white blood cells. So with an STD like gonorrhea or chlamydia, where discharge is coming from the cervix or penis, there are lots of white blood cells around. And of course you remember that WBCs are a target for HIV.
Similarly, when there is an actual break in the skin, the underlying tissue and blood cells are exposed. Studies have documented that if an ulcer or sore is present on the genitals, and you take a swab of stuff from that ulcer to culture for HIV, it’s there.
And you can easily see how a break in the skin, with exposure of the underlying tissue and blood vessels gives an entry-point for HIV.
Finally it may be that when HIV is introduced into an area of inflammation, it has a survival advantage, because the immune system is already trying to fight off one invader, and now in sneaks HIV.

18. STD Cofactor in Transmission The Biological Data
GUD: HIV cultured from genital ulcers
URETHRITIS: Urethritis increases HIV RNA levels in semen; Levels return to baseline with treatment of urethritis
CERVICITIS: Cervical inflammation leads to an increased amount of HIV in cervical secretions; Resolution reduces the amount of HIV detected
VAGINITIS: Increased pH and lack of H2O2 prolongs viral survival in vagina; IL-10 found in vaginal secretions of some women with BV can increase macrophage susceptibility
This slide outlines in more detail the types of studies done documenting biological support for STDs acting as a cofactor for HIV transmission.

19. Median concentration of HIV-1 RNA in semen among 135 HIV-infected men in Malawi w/ and w/o urethritis
Treatment
x 104 copies/ml
This study in particular is interesting; it looked at the relationship between urethritis and semen HIV levels in 135 HIV-infected men in Malawi. Compared to the 49 men without urethral discharge (the column on the far left), the 86 men with discharge had significantly higher levels of HIV in their semen. The average levels decreased about 30% within a week of treatment and were near baseline 2 weeks post treatment.
These studies not only demonstrate an increase in HIV levels in genital secretions when an STD is present, but also a reduction in HIV level with treatment of the STD.
These findings underscore the importance of appropriate screening, diagnosis and timely treatment of STDs in HIV-infected patients.
Cohen M et al. Lancet 1997; 349:

20. Effect of STD on HIV Susceptibility Summary Estimates (ORs) from Cohort Studies
M to F
F to M
GUD
2.8
4.4
HSV
insuff data
2.7
Syphilis
2.1
2.5
Chancroid
2.3
Gonorrhea
2.6
3.9
Chlamydia ns
Trichomoniasis
1.5 --
Candida
2.2 BV
1.4
Here’s where we get the “2 to 5 fold” figure for how much STDs increase the risk of HIV transmission. This paper reviewed many papers which evaluated the effects of different STDs, and shows the estimated increased susceptibility risk by the different STDs.
So we see here, for instance, that if you’re HIV-negative and you’re a man with herpes, you’re 2.7 times more likely to catch HIV from your partner than if you didn’t have herpes.
Rottingen et al STD 2001

21. Impact of Improved STD Control on HIV Infection in Tanzania
12,537 individuals in rural Tanzania followed for 2 years (1000 people from 6 control and 6 intervention communities)
And two important studies done in Africa may support the notion that treating STDs in a population can reduce the number of new HIV infection.

22. Impact of Improved STD Control on HIV Infection in Tanzania
Interventions:
Established a STD clinic and lab
Trained staff at health centers on STD treatment
Regular supply of STD medications
STD education and free condoms
Periodic visits by health educators
This study compared 6 villages that got better STD treatment with 6 village that got the same old approach that was already in place. Then after 2 years they looked at the number of new HIV infections.

23. Impact of Improved STD Control on HIV Infection in Tanzania
Results:
Lower prevalence of all STDs in intervention villages
38% reduction in incidence of HIV infection in intervention villages (1.2% vs. 1.9%)
No significant change in sexual practices (number of partners or use of condoms)
They found that there were fewer STDs in the villages that got better treatment (DUH!) but also that there were 38% fewer now HIV infection. And this was not because of different sexual practices or more condom use; these variables were about the same in all 12 villages. Actually a surprising fact about this study is that the DUH! here, the decrease in the number of STDs, was not actually as great as was expected.
Grosskurth et al, Lancet 1995, 346:530-6

24. Impact of Intermittent Mass Treatment of STDs in Uganda
Community-based randomized controlled trial of mass STD treatment and referral for symptoms or positive syphilis test
But a second, somewhat similar study however, did not find that treatment of STDs reduced the number of new HIV infections. .
Rakai, Uganda

25. Impact of Intermittent Mass Treatment of STDs in Uganda
Interventions:
People seen at home every 10 months, specimens were collected and directly observed therapy was given
Treatment: azithro 1g + cipro metro 2g
Control group: mebendazole + iron-folate + MVI
No change in local STD services
In this case, again there were 6 “intervention” villages and 6 “usual care” villages, but in this study, everybody in the intervention villages, everybody in town, was given treatment for the common STDs, gonorrhea, chlamydia and trichomoniasis.

26. Impact of Intermittent Mass Treatment of STDs in Uganda
Results:
Over 10,000 people followed for 1-2 rounds
All curable STDs decreased in intervention groups
No difference in HIV seroincidence between the groups
But when they looked at new HIV infections, the numbers were the essentially same in all 12 villages.
Why was this? Which study is right and which is wrong?
Wawer, Lancet 1999; 353:525-35

27. STD Intervention Trials Reasons for Different Outcomes
Mwanza Tanzania
Rakai Uganda
Intervention
STD Care
Continuous
Mass treatment
Intermittent
HIV prevalence 4%
16%
HSV prevalence
20% in men
50% in women
31% in men
61% in women
Proportion GUD caused by HSV
< 10%
43%
Well further analysis of these studies show that there may in fact have been some problems with the study designs from the outset, that there may have been confounding factors that were not controlled for and some conclusions drawn from the analysis may not have been valid.
But there may also be important differences in the effect of STD treatment on HIV transmission in populations that already have a heavy saturation or burden of HIV infection, like in where the base-line HIV prevalence was 16%, and populations with less base-line HIV, like the Uganda towns, with 4% base-line HIV. This has been called “early” versus “mature” stage of HIV epidemic.

28. STD/HIV Interactions and Changes in Natural History of Disease
Only very limited evidence is available
HIV progression
Evidence for an effect of transient increases in HIV viremia on disease progression is lacking
Limited evidence suggests herpes infection may increase HIV progression
STD recovery and recurrence
Some evidence for negative consequences with herpes, syphilis, chancroid, PID
I’ll touch very briefly on the subject of possible changes in the natural history of HIV or STDS because of interactions, just to say that the studies don’t help us much here. There haven’t been many studies done to look at these interactions, and those that have been done have problems with their interpretation.
Although we know that HIV viral load increases temporarily with certain STDs and with other conditions, even with many vaccinations, we don’t know if this actually affects disease progression.
There is limited evidence suggesting that herpes infection may speed HIV progression, or conversely that treatment of herpes infection may have a survival benefit.
And it does look as if some STDs are more likely to have prolonged or more severe symptoms in people with HIV infection.

29. HIV Prevention through STD Control: Applications in the U.S.
So we’ve seen that there is biologic plausibility to the idea that STDs would increase HIV transmission
And we’ve seen results from several types of studies that find this to be true.
How can this various and sometimes conflicting evidence be put to use to help slow the spread of HIV in the United States?

30. STD-related Approaches to HIV Prevention: Reducing Transmission
Screening and treatment of STDs among those at risk for HIV (reduce susceptibility)
Screening and treatment of STDs among HIV-infected patients (reduce infectivity)
Two basic principles are apparent:
We can control STDs in persons at-risk for HIV, so as to reduce their susceptibility
And we can control STDs in persons with HIV to reduce their infectiousness.

31. STDs in the U.S.
U.S. has highest rates of STDs in the industrialized nations
Heterosexual transmission of HIV increasing
STD control in U.S. likely to be beneficial because of early HIV epidemic and substantial rates of STDs
This may be a particularly effective approach in the U.S. because the U.S. has much higher rates of STDs than other developed countries such as those in Europe, and because, although there are far more cases of HIV infection in the U.S. than we might have ever been able to imagine at one time, the prevalence among the heterosexual population is still considered “low”, certainly lower than the 4% seen in the “early” stage epidemic of Uganda.
However in certain particularly hard-hit populations, for instance men who have sex with men living in the Castro in San Francisco, in fact the prevalence may be more that of the “mature” stage epidemic, so conclusions would be different.

32. Incidence of Curable STDs in Developed Countries
Gonorrhea
1995
Syphilis
1995
This slide shows Gonorrhea and syphilis rates for the U.S. and several European countries, and you can see that the U.S. is way out ahead. Embarrassing, huh? This data is rather old now but in fact the same is still true to this year.
Institute of Medicine, 1997

33. Advancing HIV Prevention A New CDC Initiative
California STD/HIV Prevention Training Center

34. Driving Concerns Behind the New Initiative Are HIV Prevention Efforts Working?
Prevention efforts to date have emphasized working with HIV-negative persons to remain uninfected
CDC estimates
40,000 new HIV infections occur in the U.S. each year
Essentially no change in this number over the last decade
One quarter of HIV infected Americans do not know they are infected
Recent increases in STDs suggest increases in unsafe sexual behaviors
STDs increase HIV transmission risk by 2-5 fold

36. Four Strategies to Further Reduce HIV Transmission
1. Make HIV testing a routine part of medical care
2. Expand HIV testing outside of traditional medical settings
3. Continue to decrease mother-to-child transmission
4. Prevent new infections by working with people diagnosed with HIV and their partners

37. Incorporating HIV Prevention into the Medical Care of Persons Living with HIV
Recommendations of the CDC, HRSA, NIH, and the HIV Medicine Association of IDSA
MMWR July 18, 2003 Volume 52, RR-12
STD detection and treatment specifically for people living with HIV is now considered an integral part of HIV prevention.

38. “Prevention with Positives” What Providers Can Do
Screen patients for HIV-transmission risk behaviors, and for STDs
Provide for risk-reduction counseling, either in-office or by referral
Facilitate notification and counseling of sex and needle-sharing partners

39. Behavior Risk Screening
Brief assessment of factors associated with HIV transmission
Assess risk routinely at all patient visits
Individualized patient-provider discussion
Self-administered written questionnaires
Training in interviewing and counseling skills can improve provider effectiveness

40. What Do I Ask to Assess Sexual Risk?
Whether the patient is sexually active
Number and gender of recent partners
Partners’ HIV status (infected, uninfected, unknown)
Types of sexual activity (vaginal, anal, oral)
Patterns of condom use
Barriers to abstinence or correct condom use
Female patients: pregnancy or contraceptive plans

41. What About Injection-Drug Related Risk?
Sharing of needles and other injection equipment
How many people the patient has shared needles with
Needle-sharing partners’ HIV status (infected, uninfected, unknown)
Patterns of needle sharing or bleaching
Barriers to ceasing drug use or adopting safer injection practices

42. STD Care for HIV-Infected Patients
Identify sexual and IDU risks
Sexual and STD history
Risk reduction counseling
Communicate and regularly reinforce prevention messages
Discuss sexual and drug-use behaviors
Positively reinforce changes to safer behavior
Help the patient form a plan of small,realistic steps to safer behavior
Partner counseling and referral services
Identify and treat STDs
CDC 2003, CSTDCA & CCLAD, 2001
The code phrase from the CDC that I know you’re all familiar with now is “Prevention with Positives”. This starts with talking openly with positive persons about their sexual and IDU risks, and their sexual and STD histories.
The information gathered in these types of honest discussions can the be used to decide when to test for STDs, and can be used more effectively in true client-centered risk-reduction counseling, and for partner and referral services.

43. Curable STD Screening HIV-Infected Patients
All at-risk patients: chlamydia, gonorrhea, syphilis
Oral or rectal exposure (3 months): gonorrhea
Women: trichomoniasis, bacterial vaginosis
Frequency of screening depends on risk behavior and local incidence of disease
And additionally, all sexually active patients should be checked routinely for chlamydia, gonorrhea and syphilis. This is true whether or not they have any symptoms, since many STDs can be present without giving symptoms.
HIV-positive women should also be checked for trichomoniasis and bacterial vaginosis.
CSTDCA & CCLAD, 2001

44. Viral STD Screening HIV-Infected Patients
Assess for genital herpes history or perform type-specific blood test
Counsel to avoid sex during symptomatic reactivation
Consider suppression to prevent transmission
Cervical Pap smear at least yearly
No recommendation for anal Pap
Finally the possibility of genital herpes infection should be discussed, since this is a very common infection and although it is not curable, the symptoms can be controlled with medication.
And women should receive routine annual Pap smears.
CSTDCA & CCLAD, 2001

45. Hepatitis Screening and Vaccination HIV-Infected Patients
All patients: Hep B vaccine
Fecal contact: Hep A vaccine
IDU:
Hep C serology
Hep B serology
Hep A vaccine
Hepatitis screening and vaccination is also critically important for people with HIV infection.Here are the hepatitis screening and vaccination recommendations.
CSTDCA & CCLAD, 2001

46. STD Cofactor Summary
STDs cause a 2-5 fold increased risk of HIV transmission
Intersecting epidemiology of STDs and and HIV in the U.S.
Diagnosis and treatment of STDs among HIV-infected patients reduces the risk of HIV transmission to negative partners
Diagnosis and treatment of STD among persons at risk of HIV may reduce this risk
So to summarize the information I’ve presented today…
Good evidence supports the idea that STDs function as an important cofactor in HIV transmission.
Taken together, the various STDs increase the transmission risks for HIV by 2 to 5 fold.
In the U.S as elsewhere, STDs and HIV travel together.
And controlling STDS can be an important method of reducing both susceptibility to and infectiousness of HIV.

47. Bibliography REVIEW ARTICLES
Royce R, et al. “Sexual transmission of HIV” NEJM 1997, 336:1072-8
Fleming D, Wasserheit J. “From epidemiological synergy to public health policy and practice: the contribution of other STDs to sexual transmission of HIV” STI 1999; 75: 3-17
Rottingen J-A, et al. A systematic review of the epidemiologic interactions between classic STDs and HIV. STD :579-97
The last few slides give references if you would like to do more reading on this subject yourself.
Thank you very much for your attention.

48. Bibliography AFRICAN TRIALS
Grosskurth H et al. Impact of improved treatment of STDs on HIV infection in rural Tanzania: Randomized controlled trial. Lancet 1995; 346:
Wawer MJ et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomized community trial. Lancet 1999; 353:
Grosskurth H et al. Control of STDs for HIV-1 prevention: Understanding the implications of the Mwanza and Rakai trials. Lancet 2000; 355:
Gisselquist D et al. Confound it: latent lessons from the Mwanza trial of STD treatment to reduce HIV transmission. Intl J STD & AIDS 2003;14:

49. Bibliography U.S. ESTIMATES
Rothenberg R, et al “The effect of treating STDs on the transmission of HIV in dually infected persons” STD 2000, 27: 411-6
GUIDELINES
CSTDCA, CCLAD. Guidance for STD clinical preventive services for persons infected with HIV. STD :460-5
MMWR :14