Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression

Of eight human herpesviruses (HHVs), often, only herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. However, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the Acquired immunodeficiency syndrome (HIV/AIDS) has only very recently been recognized. 

Therefore, screening and treating subclinical HHV infections may offer slowing of HIV infection, disease progression, and its transmission. Beside HSV-1 and HSV-2, HHV-3 a causative agent of herpes zoster remained one of the first manifestations of HIV disease before the era of highly active antiretroviral therapy (HAART). HHV-5 also known as human Cytomegalovirus infection remains a significant risk factor for HIV-associated mortality and morbidity even in HAART era. It is proposed that Cytomegalovirus viremia could be a better predictor of HIV disease progression than CD4+ T-lymphocyte count. The role of HHV-4 or Epstein-Burr virus and HHV-6, HHV-7, and HHV-8 is still being investigated in HIV disease progression. 

This review provides insight into the current understanding about these 8 HHVs, their co-pathogenesis, and role in HIV/AIDS disease progression. The review also covers recent literature in favor and against administering anti-HHV treatment along with HAART for slower AIDS progression and interrupted sexual transmission.

Below:  Opportunistic infections associated with advanced human immunodeficiency virus disease

Below:  The interaction between human herpesviruses and human immunodeficiency virus

Full article at:   http://goo.gl/3xJU69

By:  Munawwar A1, Singh S1.

• 1Department of Laboratory Medicine, Division of Clinical Microbiology and Molecular Medicine, All India Institute of Medical Sciences, New Delhi, India. 
• J Lab Physicians. 2016 Jan-Jun;8(1):5-18. doi: 10.4103/0974-2727.176228.

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Sexually Transmitted Infections and Use of Contraceptives in Women Living with HIV in Denmark - The SHADE Cohort

BACKGROUND:

No Danish guidelines for screening of sexually transmitted infections (STIs) in women living with HIV (WLWH) exist, except for annual syphilis testing. Drug-drug interaction between hormonal contraceptives and some types of highly active antiretroviral therapy (HAART) occurs. We assessed prevalence of STIs, contraceptive choices and predictors of condom use in a cohort of WLWH in Denmark.

METHODS:

WLWH consecutively enrolled during their outpatient visits from 2011 to 2012. Gynaecological examination and an interview were performed at entry and 6-month follow-up. Inclusion criteria were HIV-1 infection and ≥ 18 years of age. Exclusion criteria were pregnancy, alcohol- or drug abuse impeding adherence to the protocol. At entry, participants were tested (and where appropriate, treated according to guidelines) for Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and herpes simplex (HSV-1 and HSV-2). At follow-up, predictors of condom use were estimated in sexually active WLWH.

RESULTS:

In total, 334 of the 1,392 eligible WLWH in Denmark were included (median age and HIV duration: 42.5 and 11.3 years). Chlamydia trachomatis was present in four individuals (1 %), and six (2 %) tested positive for HSV-2 by PCR. None were positive for Neisseria gonorrhoeae, HSV-1 or had active syphilis. At follow-up, 252 (76 %) participated; 168 (70 %) were sexually active. Contraceptives were used by 124 (75 %); condoms were preferred (62 %). Having an HIV-negative partner predicted condom use (adjusted OR 3.89 (95 %CI 1.49-10.11)). In the group of participants of reproductive age without pregnancy desires 13 % used no birth-control. Possible drug-drug interaction between hormonal contraceptives and HAART was found in 13/14 WLWH receiving both kinds of medication.

CONCLUSION:

The prevalence of STIs in WLWH in Denmark was low. The need for annual STI screening is questionable. Condoms were preferred contraceptives, especially in WLWH with an HIV-negative partner. In this cohort, 13 % of WLWH of reproductive age were at risk of unintended pregnancies due to lack of birth-control. Finally, in the subgroup of WLWH receiving both hormonal contraceptives and HAART possible drug-drug interactions could occur.

Full article at:   http://goo.gl/jR36Xj

By:  Thorsteinsson K1, Ladelund S2, Storgaard M3, Rønsholt FF4, Johansen IS5, Pedersen G6, Nielsen LN7, Bonde J8, Westh H9,10, Obel N4,9, Katzenstein TL4,9,Lebech AM11,9.

• 1Department of Infectious Diseases, Hvidovre, Copenhagen University Hospital, Copenhagen, Denmark. kristina.thorsteinsson@gmail.com.
• 2Clinical Research Center, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
• 3Department of Infectious Diseases, Skejby, Aarhus University Hospital, Aarhus, Denmark.
• 4Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
• 5Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
• 6Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.
• 7Department of Infectious Diseases, Hillerød Hospital, Hillerød, Denmark.
• 8Department of Pathology, Hvidovre, Copenhagen University Hospital, Copenhagen, Denmark.
• 9Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
• 10Department of Clinical Microbiology, Hvidovre, Copenhagen University Hospital, Copenhagen, Denmark.
• 11Department of Infectious Diseases, Hvidovre, Copenhagen University Hospital, Copenhagen, Denmark.
• BMC Infect Dis. 2016 Feb 16;16(1):81. doi: 10.1186/s12879-016-1412-7. 

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Incidence of Co-Infections of HIV, Herpes Simplex Virus Type 2 and Syphilis in a Large Cohort of Men Who Have Sex with Men in Beijing, China

BACKGROUND:

The HIV-epidemic among MSM in China has worsened. In this key population, prevalence of HSV-2 and syphilis infection and co-infection with HIV is high.

METHODS:

A longitudinal study was conducted (n = 962) in Beijing, China, with three overlapping cohorts (n = 857, 757 and 760) consisting of MSM that were free from pairs of infections of concern (i.e. HIV-HSV-2, HIV-syphilis, HSV-2-syphilis) at baseline to estimate incidence of HIV, HSV-2, syphilis, and those of co-infection.

RESULTS:

The incidence of HIV, HSV-2 and syphilis in the overall cohort was 3.90 (95% CI = 2.37, 5.43), 7.87 (95% CI = 5.74, 10.00) and 6.06 (95% CI = 4.18, 7.94) cases per 100 person-years (PYs), respectively. The incidence of HIV-HSV-2, HIV-Syphilis and HSV-2-Syphilis co-infections was 0.30 (95% CI = 0.29, 0.88), 1.02 (95% CI = 0.13, 2.17) and 1.41 (95% CI: 0.04, 2.78) cases per 100 PYs, respectively, in the three sub-cohorts constructed for this study.

CONCLUSIONS:

The incidence of HIV, HSV-2 and syphilis was very high and those of their co-infections were relatively high. Such co-infections have negative impacts on the HIV/STI epidemics. Prevention practices need to take such co-infections into account.

Below:  Associations of the socio-demographic characteristic with loss of follow-up among MSM in Beijing, China

Full article at:   http://goo.gl/TrgSPE

By:  Li D1, Yang X1,2, Zhang Z1, Wang Z2, Qi X1, Ruan Y3, Zhou Y4, Li C2, Luo F1, Lau JT2.

• 1Chaoyang Center for Disease Control and Prevention, Beijing, PR China.
• 2Center for Health Behaviours Research, The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong SAR, Hong Kong, China.
• 3State Key Laboratory for Infectious Disease Prevention and Control (SKLID), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
• 4Department of Epidemiology and Health Statistics, School of Public Health, Soochow University, Suzhou, Jiangsu, China.
• PLoS One. 2016 Jan 28;11(1):e0147422. doi: 10.1371/journal.pone.0147422. eCollection 2016. 

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Correlates to Seroprevalent Herpes Simplex Virus Type 2 among Rural Appalachian Drug Users

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and, along with substance abuse, an important HIV risk factor. Therefore, the purpose of this study was to examine HSV-2 seroprevalence in a sample of drug users in rural Appalachia. 

Rural Appalachian individuals age 18 or older reporting non-medical use of prescription opioids, heroin, crack/cocaine, or methamphetamine in the past 6 months (n = 499) were included. Behavioral, demographic, and sexual network data were collected using interviewer-administered questionnaires. 

Participants' serum was tested for HSV-2 antibodies using the Biokit rapid test (Lexington, MA). The estimated population seroprevalence of HSV-2 was 14.4% (95%CI: 9.6-19.4%). Only 8.8% were aware of being HSV-2+, and unprotected sex was reported in 80% of serodiscordant sexual relationships. 

In a multivariate model, female gender, age, older age at first oral sex, and frequency of unprotected sex in the sexual network were independently associated with HSV-2 seropositivity. Despite lower seroprevalence than that reported in similar studies of substance abusers, targeted interventions to reduce sexual risk behavior are warranted in this underserved population. 

Network-informed approaches with particular focus on women, older individuals, and those engaging in frequent unprotected sex are recommended.

Purchase full article at:   http://goo.gl/F5Ecrl

By:  Stephens DB1,2, Young AM2,3, Mullins UL2, Havens JR1,2.

• 1Department of Behavioral Science (https://behavioralscience.med.uky.edu/), University of Kentucky College of Medicine, Lexington, Kentucky.
• 2Center on Drug and Alcohol Research, University of Kentucky College of Medicine, Lexington, Kentucky.
• 3Department of Epidemiology, University of Kentucky College of Public Health, Lexington, Kentucky. 
• J Med Virol. 2016 Mar;88(3):512-20. doi: 10.1002/jmv.24358. Epub 2015 Aug 27.

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Predictors of the Sexual Well-being of Individuals Diagnosed with Herpes and Human Papillomavirus

Research suggests that having a sexually transmitted infection (STI) such as genital herpes and human papillomavirus (HPV) can negatively affect sexual well-being. However, there is little research examining factors associated with poorer sexual well-being among individuals with a STI. 

This study investigated the extent to which stigma experiences, individual characteristics, and STI characteristics were associated with multiple aspects of sexual well-being among individuals diagnosed with herpes and/or HPV. Participants were an average of 36 years old (SD = 11.58) and included 188 individuals with herpes and/or HPV who completed measures of sexual activity, sexual problems, and sexual cognitive-affective factors. 

The results showed that experiences of stigmatization were the most important predictors of sexual well-being. Participants who perceived were stigmatized by others as well as those who internalized negative social attitudes to a greater extent reported poorer sexual well-being across all dimensions, over and above individual and STI characteristics. The implications of these findings for sexual health professionals are discussed.

Purchase full article at:   http://goo.gl/dPqW6R

By:  Foster LR1, Byers ES2.

• 1Department of Psychology, University of New Brunswick, P.O. Box 4400, Fredericton, NB, E3B 5A3, Canada.
• 2Department of Psychology, University of New Brunswick, P.O. Box 4400, Fredericton, NB, E3B 5A3, Canada. byers@unb.ca.
• Arch Sex Behav. 2016 Feb;45(2):403-14. doi: 10.1007/s10508-014-0388-x. Epub 2014 Nov 19. 

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Correlates pf Prevalent HIV Infection among Adults & Adolescents in Kisumu, Kenya

We estimated HIV prevalence and identified correlates of HIV infection among 1106 men and women aged 16–34 years residing in Kisumu, Kenya. Demographic, sexual, and other behavioural data were collected using audio computer-assisted self-interview in conjunction with a medical examination, real-time parallel rapid HIV testing, and laboratory testing for pregnancy, gonorrhoea, chlamydia, syphilis, and herpes simplex virus type 2. Multivariate logistic regression was used to identify variables associated with prevalent HIV infection by gender. 

• Overall HIV prevalence was 12.1%. 
• HIV prevalence among women (17.1%) was approximately two and one half times the prevalence among men (6.6%). 
• Odds of HIV infection in men 
• increased with age and 
• were greater among those who were uncircumcised 
• and those who had an herpes simplex virus type 2 positive test result. 
• Odds of prevalent HIV infection among women also 
• increased with age. 
• Women who tested herpes simplex virus type 2 positive had more than three times the odds of prevalent HIV infection compared with those who tested herpes simplex virus type 2 negative. 

Tailored sexual health interventions and programs may help mitigate HIV age and gender disparities.

Correlates of HIV infection among men, Kisumu Incidence Cohort Study, Kenya, 2007–2010.

	HIV Prevalence at Screening		Bivariate		Multiple Regression
	N	%	OR (95% CI)	p-value	aOR** (95% CI)	p-value
Age*			1.20 (1.11, 1.29)	<.0001	1.21 (1.07, 1.35)	.0017
Marital status				.0373		.2976
Single/never married	21	5.3	Ref		Ref
Married/living as married	12	9.8	1.95 (0.93, 4.08)		0.47 (0.14, 1.57)
Separated/divorced/widowed	2	25.0	6.00 (1.14, 31.54)		2.08 (0.24, 18.07)
Religion				.5776
Roman Catholic	11	5.2	Ref
Protestant or other Christian	15	6.8	1.32 (0.59, 2.94)
Muslim/Nomiya/Other	7	8.1	1.58 (0.59, 4.23)
No religion	2	13.3	2.78 (0.56, 13.90)
Highest education level				.0030		.2421
Never attended school	6	27.3	9.25 (2.67, 32.08)		4.47 (0.95, 21.06)
Primary school	12	7.6	2.01 (0.74, 5.51)		1.41 (0.42, 4.74)
Secondary school	11	5.7	1.48 (0.54, 4.10)		1.15 (0.38, 3.50)
Post-secondary schoola	6	3.9	Ref		Ref
Currently working				.8029
Yes	16	6.9	1.09 (0.55, 2.17)
No	19	6.4	ref
Lifetime number of sexual partnersb				.3646
1–2	2	4.4	Ref
3–4	7	4.7	1.09 (0.22, 5.41)
5 or more	25	7.9	1.88 (0.43, 8.20)
Ever had anal sex				.2108		.1577
Yes	3	3.4	0.46 (0.14, 1.55)		0.37 (0.09, 1.48)
No	31	7.0	Ref		Ref
Ever had oral sex				.9831
Yes	9	6.6	1.01 (0.46, 2.21)
No	26	6.6	Ref
Ever been forced into sex				.5502
Yes	6	8.2	1.32 (0.53, 3.30)
No	29	6.4	Ref
Number of sexual partners in the past three monthsb				.9009		.4761
0	5	14.3	Ref		Ref
1	5	4.4	0.27 (0.07, 1.00)		0.31 (0.06, 1.59)
2–3	13	6.1	0.39 (0.13, 1.18)		0.34 (0.08, 1.39)
4 or more	12	7.3	0.47 (0.16, 1.44)		0.42 (0.10, 1.74)
Any unprotected vaginal or anal sex in the past three months				.6114
Yes	3	4.4	1.38 (0.40, 4.70)
No	24	6.0	Ref
Sex during special occasions in the past three months				.6831
Yes	10	5.5	0.85 (0.39, 1.86)
No	20	6.4	Ref
STI history				<.0001		.0966
Never	19	4.3	Ref		Ref
Not recent	10	15.4	4.03 (1.78, 9.12)		2.09 (0.76, 5.78)
Recent (past three months)	6	24.0	7.00 (2.51, 19.53)		3.40 (0.99, 11.65)
HSV-2 results				<.0001		.0489
Positive	12	20.7	6.82 (3.04, 15.29)		3.13 (1.12, 8.73)
Indeterminate	7	16.7	5.23 (2.02, 13.55)		3.04 (0.95, 9.71)
Negative	16	3.7	Ref		Ref
Circumcision as confirmed by physical examination (men)				.0070		.0109
Uncircumcised	31	8.9	4.29 (1.49, 12.35)		4.42 (1.41, 13.89)
Circumcised	4	2.2	Ref		Ref

aPost-secondary education includes technical/vocational training, college, or university.

bPersons with whom the participant had vaginal or anal sex.

*Continuous variable.

**Odds ratios and confidence intervals adjusted for all variables listed in the column (i.e. all variables with p <.25 in bivariate models).

Correlates of HIV infection among women, Kisumu Incidence Cohort Study, Kenya, 2007–2010.

	HIV Prevalence at Screening		Bivariate		Multiple Regression
	N	%	OR** (95% CI)	p-value	aOR** (95% CI)	p-value
Age*			1.17 (1.11, 1.23)	<.0001	1.16 (1.04, 1.29)	.0085
Marital status				<.0001		.9456
Single/never married	36	10.3	Ref		Ref
Married/living as married	44	24.2	2.76 (1.70, 4.48)		1.00 (0.34, 2.97)
Separated/divorced/widowed	16	41.0	6.03 (2.92, 12.45)		1.26 (0.29, 5.52)
Religion				.8482
Roman Catholic	48	17.3	Ref
Protestant or other Christian	28	15.3	0.87 (0.52, 1.44)
Muslim/Nomiya/Other	17	19.5	1.16 (0.63, 2.15)
No religion	4	18.2	1.07 (0.35, 3.29)
Highest education level				.0096		.3554
Never attended school	8	33.3	4.21 (1.53, 11.61)		4.77 (0.49, 46.07)
Primary school	48	21.2	2.26 (1.19, 4.28)		3.05 (0.84, 11.08)
Secondary school	27	14.4	1.42 (0.72, 2.83)		2.31 (0.66, 8.08)
Post-secondary schoola	14	10.6	Ref		Ref
Currently working				.0038		.6743
Yes	47	23.3	1.92 (1.24, 2.99)		0.83 (0.35, 1.96)
No	50	13.6	Ref		Ref
Lifetime number of sexual partnersb*				.0010		.2903
1–2	11	7.8	Ref		Ref
3–4	40	17.5	2.53 (1.25, 5.12)		2.52 (0.75, 8.47)
≥5	41	24.3	3.81 (1.88, 7.74)		1.68 (0.46, 6.16)
Ever had anal sex				.0940		.5813
Yes	19	12.5	0.63 (0.37, 1.08)		0.73 (0.24, 2.21)
No	76	18.5	Ref		Ref
Ever had oral sex				.5928
Yes	17	15.2	0.86 (0.48, 1.52)
No	78	17.3	Ref
Ever been forced into sex				.3499
Yes	29	19.5	1.26 (0.78, 2.04)
No	68	16.1	Ref
Number of sexual partners in the past three monthsb				.6828
0	6	17.1	Ref
1	51	15.6	0.89 (0.35, 2.27)Ref
2–3	28	18.0	1.06 (0.40, 2.79)
4 or more	14	19.4	1.17 (0.41, 3.35)
Any unprotected vaginal or anal sex in the past three months				.0725		.5167
Yes	70	18.1	1.96 (0.94, 4.10)		0.70 (0.24, 2.06)
No	9	10.1	Ref		Ref
Sex during special occasions in the past three months				.7423
Yes	19	17.9	1.10 (0.63, 1.92)
No	71	16.6	Ref
STI history				<.0001		.9115
Not recent	10	15.4	4.03 (1.78, 9.11)		1.38 (0.32, 5.90)
Recent (past three months)	6	24.0	7.00 (2.51, 19.53)		1.00 (0.08, 11.81)
Never	19	4.3	Ref		Ref
HSV-2 results				<.0001		.0114
Positive	76	35.5	12.92 (6.94, 24.06)		3.85 (1.38, 10.71)
Indeterminate	9	23.1	7.04 (2.78, 17.82)		0.88 (0.14, 5.59)
Negative	13	4.1	Ref		Ref
Pregnant as confirmed by lab test (women)				.0963		.9837
Yes	8	28.6	2.06 (0.88, 4.82)		0.98 (0.09, 10.66)
No	88	16.3	Ref		Ref
Used birth control pills to delay or avoid pregnancy in the past three months (women)				.0484		.5334
Yes	33	23.1	1.96 (1.01, 3.82)		1.38 (0.51, 3.74)
No	15	13.3	Ref		Ref
Used injections to delay or avoid pregnancy in the past three months (women)				.0355		.9940
Yes	33	24.1	2.02 (1.05, 3.90)		1.00 (0.38, 2.67)
No	16	13.6	Ref		Ref

aPost-secondary education includes technical/vocational training, college, or university.

bPersons with whom the participant had vaginal or anal sex.

*Continuous variable.

**Odds ratios and confidence intervals adjusted for all variables listed in the column (i.e. all variables with p <.25 in bivariate models).

Full article at:   http://goo.gl/NFjq0f

By:  Anne Gumbe,1 Eleanor McLellan-Lemal,2 Deborah A Gust,2 Sherri L Pals,2 Kristen Mahle Gray,2 Richard Ndivo,1Robert T Chen,2 Lisa A Mills,3 and Timothy K Thomas3, for the KICoS Study Team1

¹Kenya Medical Research Institute, Kisumu, Kenya

²Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of HIV/AIDS Prevention, Atlanta, GA, USA

³Centers for Disease Control and Prevention, HIV-Research Branch, Kisumu, Kenya

Corresponding author: Anne Gumbe, International AIDS Vaccine Initiative, ABC Place (Building 2,3rd Fl) Waiyaki Way, PO Box 340 KNH, Nairobi, Kenya. Email: gro.ivai@ebmuga

Int J STD AIDS. 2015 Nov; 26(13): 929–940.

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