SVEMSIDAECU

Author Information

Department of Medicine, Ben Taub General Hospital and Baylor College of Medicine, Houston, Texas, USA.

Received 23 June, 2009

Revised 6 August, 2009

Accepted 13 August, 2009

Correspondence to Wayne X. Shandera, Deparment of Medicine, Ben Taub General Hospital and Baylor College of Medicine, Houston, TX 77098, USA. Tel: +1 713 873 3389; fax: +1 713 798 6400; e-mail: shandera@bcm.tmc.edu

The reasons a medication regimen may be changed are multiple and include lack of efficacy, patient noncompliance or dissatisfaction, adverse effects, and resolution of the indication for the medication. With HIV regimens, toxicities and patient nonadherence are prominent. A study of such treatment modifications is reported by Messou et al. ^[1], an analysis of a cohort in a low-income suburb of Abidjan, Cote d'Ivoire, in a large clinic funded through a nonprofit organization with significant support from several international organizations. The authors report that toxicity is a major but by no means the sole reason for change of therapy, similar to data from other developing nations in Africa ^[2,3].

Toxicity associated with anti-HIV therapy dates back to its onset with the readily identified toxicities of zidovudine [macrocytic anemia, myopathy, central nervous system (CNS) disturbances]. Toxicities were increased with the recognition of metabolic disturbances especially prominent with use of protease inhibitors. Improved drug formulations, better pharmacokinetics, and development of agents with fewer adverse effects led to the current status whereby many patients are managed successfully in the developed world with once-a-day therapy. Such simpler regimens are infrequently available in the developing world where the percentages receiving any antiretroviral therapy are woefully low ^[4].

This descriptive epidemiology by Messou et al. ^[1] is from sub-Saharan Africa where live 65% of all people infected with HIV. The report is provided in a nation receiving funding from the United States government-based President's Emergency Plan for AIDS Relief (PEPFAR) as well as other prominent nongovernmental organizations (NGO) in a clinic with a remarkably low level of antiretroviral discontinuance, program efficiency, good support, and low patient costs. In settings without such organizational and international support, the results may be less satisfactory. In one Asian clinic, for example, 19% of changes were associated with issues relating to cost^[5]. In Messou's program, patients spent only about $12 per year for an entire family (mean size, 6.7), costs that pale by comparison with the estimated $200 per case spent by the Ivorian National government, and both costs pale when one considers the many additional indirect costs associated with the outbreak, such as lost productivity, lost parenting, needs of employers for retraining, and education costs for prevention which impacts the non-HIV infected.

Providing antiretroviral treatment for the very poor in the developing world will incur costs associated with improving surveillance and access as well as costs attendant with sustaining a larger infrastructure that encompasses both preventive and therapeutic goals including the increasing problems of viral resistance ^[4]. A key issue is determining when cost efficacy is established, when the costs of care lessen the many indirect costs and the costs of prevention diminish future case loads ^[6].

The study reported herein describes an ideal situation, one hard to replicate in areas without prominent international funding (that constitutes much of the world) but encouraging in its findings. Accepting this fact, what were the findings in addition to cost efficiency and how are they relevant? The authors noted that the antiretroviral stavudine was particularly attendant with adverse effects and this confirms the findings of other authors ^[3]. Such concerns are part of the US-based Department of Health and Human Services (DHSS) recommendations in which stavudine is not recommended for primary therapy because of toxicities including peripheral neuropathy, hepatic steatosis, and lactic acidosis ^[7]. Guidelines for the developing world should as well consider relegating stavudine to secondary status as newer agents become available.

In the authors' experience efavirenz was often substituted for reasons of pregnancy, and CNS side effects were infrequent. This latter may reflect the perspicacity of Ivorian physicians in not prescribing the agent to patients with complex neurologic or psychiatric conditions. Efavirenz is unique among antiretroviral agents in its potential teratogenicity (which needs further study) but the importance of this adverse effect in potentially childbearing women cannot be underestimated ^[8].

The authors emphasize the interactions of efavirenz with antituberculous therapy. The number of individuals who die annually co-infected with Mycobacteria tuberculosis and the HIV is nearly 500 000 ^[9]. The many options for co-treatment are well reviewed elsewhere ^[10]. The frequency with which nevirapine was changed to an alternative therapy (and the recommended alternative efavirenz is often untenable) is worth noting.

This study represents a type of reverse translational research in which findings from the clinic, bedside, and the public health office are made evident to basic scientists in the hope that new basic discoveries show societal relevance. Good descriptive epidemiologic studies such as this one fulfill that goal and should be the incentive needed to push for the development of new forms of therapy and the dissemination of already recognized forms of therapy that are less toxic than stavudine, safer in pregnancy than efavirenz, and attendant with fewer adverse drug interactions than nevirapine.

Finally, the current study suggests that if enough funds were put into making highly-active antiretroviral therapy (HAART) available at low cost (as with the cited program), if patients were as reliant and adherent as those in this experience, then the pandemic of AIDS could begin to see some type of resolution. If the majority of HIV-infected individuals were identified, if the appropriate patients go on therapy, and if corresponding viral loads in these cases are reduced, it logically follows that transmissibility will fall and the pandemic could eventually resolve. This requires a global commitment. The global amount needed to provide preventive and therapeutic care for HIV/AIDS was estimated at over $20 billion for 2007 and appears to be growing almost exponentially. If the US expenses of over $2 billion in developmental assistance for HIV/AIDS in 2007 had been spent annually over the 8 years since the onset of military conflicts in Iraq and later Afghanistan, the expenditure of $16 billion would amount to not even 2% of the $900 billion these two wars have cost the American public. Perhaps we should redeploy our generals as epidemiologist and our soldiers as pill sharers.

References

1. Messou EXA, Anglaret X, Duvignace J, Konan-N'Dri E, Komena E, Gnokoro J, et al. Antiretroviral treatment changes in adults from Cote d'Ivoire: the roles of tuberculosis and pregnancy. AIDS2009 (this issue).

2. Forna F, Liechty CA, Solberg P, Asiimwe F, Were W, Mermin J, et al. Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda. J Acquir Immune Defic Syndr 2007; 44:456-462.

3. Boulle A, Orrel C, Kaplan R, Van Cutsem G, McNally M, Hilderbrand K, et al. Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort. Antivir Ther 2007; 12:753-760.

4. Moatti JP, N'Doye I, Hammer SM, Hale P, Kazatchkine M. Antiretroviral treatment for HIV infection in developing countries: an attainable new paradigm. Nat Med 2003; 9:1449-1452.

5. Kumarasamy N, Vallabhaneni S, Cecelia AJ, Yepthomi T, Balakrishnan P, Saghayam S, et al. Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India. J Acquir Immune Defic Syndr 2006; 41:53-58.

6. Stover J, Bertozzi S, Gutierrez JP, Walker N, Stanecki KA, Greener R, et al. The global impact of scaling up HIV/AIDS prevention programs in low- and middle-income countries. Science (New York, NY) 2006; 311:1474-1476.

7. DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.Washington, DC: DHHS; 2008.

8. Tonwe-Gold B, Ekouevi DK, Viho I, Amani-Bosse C, Toure S, Coffie PA, et al. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach. PLoS Med 2007; 4:e257.

9. Donald PR, van Helden PD. The global burden of tuberculosis-combating drug resistance in difficult times. N Engl J Med 2009; 360:2393-2395.

10. CDC, DHHS. Guidelines of prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Washington, DC: DHHS; 2008.

Keywords:

cost; developing countries; HIV; HAART

Male circumcision to prevent heterosexual HIV transmission gets (another) green light, but traditional circumcision in Africa has 'shocking' number of complications

AIDS:

2 January 2010 - Volume 24 - Issue 1 - p N1-N2

doi: 10.1097/QAD.0b013e32832faec0

Notes and Quotes

Male circumcision to prevent heterosexual HIV transmission gets (another) green light, but traditional circumcision in Africa has 'shocking' number of complications

Crabb, Charlene

In 2005 and 2007, a trio of clinical trials in Africa found that circumcising young men in modern medical settings reduces the risk of acquiring HIV from female partners by approximately 60%. In April, a second meta-analysis of the three studies, this time conducted by the Cochrane Collaboration, concluded that no further clinical trials are needed to make the point about the efficacy of circumcision to prevent HIV infection. The findings echo those of a meta-analysis reported in this journal last year by Helen Weiss and collaborators.

But as governments in Africa initiate circumcision programmes in communities that do not normally practice it, a serious concern is whether the procedure can be provided safely to large numbers of adult men in developing countries. A recent study emphasizes that worry. Researchers report 'shocking' and 'unacceptable' rates of a Pandora's box of complications, some life-threatening, resulting from circumcisions performed as part of traditional coming-of-age rites in Kenya. (Bull World Health Organ 2008, 86:669-677.)

'Our study demonstrates that as we roll out circumcision and try to make it widely available in health facilities, it's going to have to be done carefully, and it's going to require some resources,' says Robert Bailey of University of Illinois, Chicago, who led the current study, as well as one of the seminal 2007 clinical trials on circumcision and HIV infection. 'It's alarming that (traditional circumcision) has been going on for so long with such high rates of adverse events.'

The prospective study followed 1007 young men, aged 5-21 years, circumcised during the July-August 2004 circumcision season in the Bungoma district, Kenya. The men hailed from the Bukusu ethnic group, who consider circumcision obligatory and have practiced it for centuries. The participants had either a 'traditional' circumcision performed in a village or within a household compound, or a 'medical' circumcision performed by someone the participant considered to be a clinician in a hospital, health centre, dispensary or private office.

To document complications, the researchers interviewed the men 30-89 days after circumcision. Twenty-four men were directly observed during circumcision and after 3, 8, 30 and 90 days. The criteria for adverse events were the same as used in the earlier clinical trial.

However, after interviewing approximately two-thirds of participants and directly following the 24 cases, the researchers found 'very high rates' of complications. They decided to directly examine and interview the remaining 298 men, ranging from 45 to 89 days after circumcision.

Overall, 35.2% men circumcised traditionally suffered some form of postoperation complication. Among the men circumcised medically the adverse event rate was significantly lower, 17.7%. However, both rates are well above that of 1.7% observed in the Bailey-led clinical trial in Kisumu, Kenya, as well as those of infant circumcision rates in developed countries.

The types of adverse events ranged from infection, excessive bleeding and pain to permanent after effects such as excessive scarring, erectile dysfunction and mutilation of the tip of the penis, or glans. The rates might have been even higher, the authors note, if they had not intervened to redress wounds (20 cases) and give antibiotics (2 cases). One patient likely would have died if he had not been taken to hospital.

The problems stem from poor training and a lack of proper equipment and medical supplies. Inventories conducted by the researchers of three hospitals, one health centre, and 14 private clinics revealed, for example, that only half of the public health centres had working autoclaves compared with just one-fifth of the private facilities. Approximately, half of both private and public facilities had no sutures. The surgical kits of the 20 traditional circumcisers interviewed consisted of a knife made by the boy's family, a pinch of clay to help grasp the foreskin, herbs to staunch bleeding, and leaves or, perhaps, gauze and bandages, to wrap the penis.

The findings will likely further fuel discussions on how best to roll out circumcision as part of HIV prevention programmes. But Bailey hopes it will also stimulate action in areas where circumcision is already part of the cultural landscape. 'I'm afraid that 10 years from now, when we've put resources into circumcision in traditionally noncircumcising societies, we're going to look back and say, wait a minute, what were we doing in traditionally circumcising societies in which young boys were getting mutilated, and we ignored it.'

Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation

AIDS:

24 September 2010 - Volume 24 - Issue 15 - p 2375–2380

doi: 10.1097/QAD.0b013e32833dfad1

Clinical Science

Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation

Tosini, William^a,b; Muller, Philippe^c; Prazuck, Thierry^d; Benabdelmoumen, Ghania^b; Peyrouse, Eric^e; Christian, Bernard^c; Quertainmont, Yann^f; Bouvet, Elisabeth^a,b; Rabaud, Christian^a,c

Author Information

^aGroupe d'Etude sur le Risque d'exposition des Soignants aux Agents Infectieux (GERES), France

^bHôpital Bichat Claude-Bernard, Paris, France

^cCOREVIH Lorraine Champagne Ardenne, Centre Hospitalier et Universitaire, Nancy, France

^dCentre Hospitalier Régional, Orléans, France

^eHôpital Sainte Marguerite, Marseille, France

^fHôpital Bicêtre, Paris, France.

Received 8 September, 2009

Revised 1 July, 2010

Accepted 6 July, 2010

Correspondence to Dr William Tosini, GERES, Université Paris Diderot Paris 7, UFR de Médecine site Bichat, 16 rue Henri Huchard, 75890 Paris Cedex 18, France. E-mail: wilto@libero.it

Abstract

Objective: To evaluate the tolerability of HIV postexposure prophylaxis (PEP) with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation (TDF/FTC+LPV/r).

Design: Multicentric observational prospective study.

Method: Adults with an HIV transmission risk in the past 48 h were eligible. Baseline sociodemographic characteristics, description of exposure event, and HIV serostatus of the source patient were collected. Laboratory monitoring for toxicity and a clinical evaluation were performed; adherence and side effects were recorded using a standardized form on day 0, 15, and 28.

Results: Between November 2006 and June 2008, 249 participants were included in 10 French hospitals. Mean age was 31.5 ± 10 years. Sex ratio male/female was 1.96. Exposure events are as follows: occupational exposure, 40 (16%); sexual intercourse, 204 (82%); and other, 5 (2%). Tolerability could be evaluated in 188 cases. In 22 cases, PEP was discontinued for adverse effects before day 28, including two cases of skin rash related to TDF/FTC prescription, one renal lithiasis related to LPV/r prescription, and one rhabdomyolysis. One hundred and sixty-six persons completed the 28 days of PEP with tolerability judged as good in 96 (58%) individuals. Among everyone who experienced at least one side effect, 78% reported diarrhea, 78% asthenia, and 59% nausea and/or vomiting.

Conclusion: Considering data of previous studies performed using similar methodology, the dropout rate due to adverse events appeared significantly lower in TDF/FTC+LPV/r tablet formulation than those in zidovudine/lamivudine (ZDV/3TC)+nelfinavir (P < 0.0001), ZDV/3TC+lopinavir/ritonavir soft gel capsules (P < 0.01), and 3TC+TDF+atazanavir boosted by ritonavir (P < 0.05) and should be considered as standard of care concerning HIV PEP.

Global HIV surveillance among MSM: is risk behavior seriously underestimated?

AIDS:

24 September 2010 - Volume 24 - Issue 15 - p 2301–2303

doi: 10.1097/QAD.0b013e32833d207d

Opinion Piece

Global HIV surveillance among MSM: is risk behavior seriously underestimated?

Bengtsson, Linus; Thorson, Anna

Author Information

Karolinska Institutet, Department of Public Health Sciences, Division of Global Health/IHCAR, 171 77 Stockholm, Sweden.

Received 14 January, 2010

Revised 3 June, 2010

Accepted 10 June, 2010

Correspondence to Linus Bengtsson, Institutionen för folkhälsovetenskap Global hälsa/IHCAR, Nobels väg 9, Karolinska Institutet, 171 77 Stockholm, Sweden. E-mail: linus.bengtsson@ki.se

MSM face a devastating HIV epidemic globally ^[1]. Odds ratios for HIV infection among MSM, as compared to the general population, are estimated at 7.8 and 23.4 in low and middle-income countries, respectively ^[2]. Forty-two percent of new HIV infections in Asia have been forecast to occur among MSM in 2020 ^[3].

HIV-related forecasts should rely on unbiased estimates of core epidemiological indicators, for example HIV prevalence and risk behavior. There are, however, major challenges inherent in performing probability sampling among hard-to-reach populations like MSM. The development of a chain-referral method, named respondent-driven sampling (RDS) in 1994, marked an important methodological achievement ^[4]. By 2007, more than 120 HIV-related RDS studies in at least 28 countries had been performed among hard-to-reach populations ^[5,6]. As a result of the method's appeal, the global epidemiological evidence base for HIV-related surveillance and research among MSM is increasingly reliant upon the RDS method.

Whereas we consider the RDS method to be a promising sampling methodology for HIV-related MSM research in many settings, we here present a hypothesis that questions the validity of important RDS study outcomes in the MSM population.

Implementation of a respondent-driven sampling study

At the start of an RDS study researchers recruit a few study participants (seeds) belonging to the risk population of interest. The participants are, after completion of, for example, an HIV test and a questionnaire, given invitation coupons (usually three) to give to friends within the population under study. These friends in turn invite other friends and long recruitment chains are created. Analytical proofs and simulations have shown that the RDS method, under a limited number of assumptions, allows calculations of unbiased estimates of population proportions and that the final composition of the sample is independent from the characteristics of the seeds ^[7,8]. For methodological discussions, please see selected references ^[9–12].

Adjusting for different inclusion probabilities

A major difference between analysis of data from an RDS sample and a standard sample is that the sample proportion of a characteristic (e.g. the proportion of the population reporting sexual risk behavior) is adjusted by the possibilities the group members have for being invited into the study by other persons in the population. To formalize and measure inclusion probabilities, each participant is asked about the size of his/her social network. For MSM this usually includes a question equivalent to: ‘How many MSM do you know, who also know you and whom you have met during the last month/last six months?’. The underlying assumption is that a person who only knows one other person within the population under study has merely one chance of being invited to participate, whereas a person with 100 contacts has 100 chances of being invited.

The proportion of persons with characteristic A in the population can be estimated by the RDSII estimator:

Equation (Uncited)
Image Tools

where d_i is the personal network size (degree) of individual i and S is the set of all individuals in the sample. The RDSII estimator gives point estimates equivalent to the earlier RDS/DS estimator but has analytical advantages ^[8].

Are HIV indicators underestimated?

Imagine a gay man (MSM) maintaining a large network for dating and sex. In addition, he has a smaller set of close MSM friends. We hypothesize that his chances of being invited to a study about HIV is largely dependent on his number of close friends rather than on his number of casual sexual and dating partners (past, current or potential), as fear of being associated with HIV is well documented in numerous settings ^[13]. Studies have shown that HIV-positive MSM less frequently disclose their HIV status to casual sexual partners than to a stable partner ^[14]. Such data possibly support the common sense notion that sensitive issues such as those related to HIV and sexual behavior are more difficult to communicate about with casual sexual partners than with close friends.

Unfortunately little empirical evidence that could illuminate this issue has been reported from RDS studies among MSM. One Brazilian study ^[15] published details on the proportion of participants who were recruited by a sexual, as opposed nonsexual contact and specifically if the sexual contact was a casual or stable partner. In this study, which included 626 participants, 11% reported being recruited by a ‘boyfriend or spouse’, but only 2% said that they were recruited by an ‘occasional sexual partner’.

On the basis of data from Shanghai, China ^[16], let us assume that the gay man in our example above has a network of 12 male sexual contacts and five close MSM friends, and that he counts his sexual contacts as men that he knows and who knows him and whom he has met during the last 6 months. The data referred to in the example describe 15% of the sample reporting 6–20 male anal sex partners during the last 6 months. Non-anal sex partners were not reported. Although the current RDS methodology assumes that any of these (12 + 5) = 17 members of his network may invite him into the study, he would, given our hypothesis, really only stand a chance of getting invited by one of his five close friends. Thus, his chances of being recruited to the study are less than a third of what would be predicted by network size alone.

If we assume, based on the Chinese data, that 15% of the men in the sample share the characteristics of this man, while actually standing similar chances to be invited into the study as the rest of the sample, that is by five close friends, the network-adjusted estimated population proportion of this group with most partners would then only be half of the true value (7.4% instead of the correct figure 15%).

The overwhelming number of RDS studies among MSM report only network size-adjusted proportions of MSM. The few that report both crude and adjusted proportions for the group with the highest number of sexual partners show adjusted proportions that are as low as a third of the crude, unadjusted proportions ^[17–19].

Thus, adjusting sample proportions by a reported social network size that includes sexual contacts, which in itself is a study outcome, can potentially introduce a considerable bias. Such bias is from a surveillance point of view very troubling in a population in which anal sex is not practised safely. Hence, it seems warranted to show that any adjustment by network size is based on good empirical evidence. Such evidence is not available today.

During the past decade, it has become increasingly clear that concurrent sexual relations are very important for the sexual spread of HIV ^[20]. Hence, biases in indicators that relate to multiple partnerships are especially serious as they may obscure a correct understanding of the major drivers of the HIV epidemic among MSM. If our hypothesis holds true, it may also be particularly relevant to the high-risk group of male sex workers. Along the same line of reasoning, we hypothesize that many of these men will know a large number of regular clients, who may be included in their reported social network, whereas they would rarely be recruited into an HIV study by these clients. Consequently, the proportion of men selling sex could be severely underestimated, as could the sex workers' relatively large contribution to the average level of risk behavior and HIV prevalence within the global MSM population.

Conclusion

Current adjustment of sample proportions by network size may introduce considerable bias in HIV-related RDS studies among MSM, resulting in an underestimation of the proportion of the population with high partner numbers. As HIV prevalence is correlated with having casual or concurrent sexual partners, HIV prevalence could likewise be underestimated.

We recommend future RDS studies among MSM to ask participants for the composition of their MSM network (number and types of contacts). Together with participants' reports of whom they were actually recruited by, this would enable an evaluation of the presented hypothesis and consequently a rephrasing of the social network question in a way that reflect true inclusion probabilities.

In conclusion, RDS constitutes an important leap forward in the provision of evidence-based information to curb the spread of HIV among millions of stigmatized and at-risk men. We therefore urge funders and the research community to increase their efforts in support of methodological research in MSM sampling methodologies with a particular emphasis on the stated hypothesis.

Acknowledgements

L.B. conceived of the idea and made the literature search. A.T. contributed with additional ideas and L.B. and A.T. wrote the manuscript together. The authors wish to thank Xin Lu, Karolinska Institutet, for valuable discussions. We are grateful to Sida who has supported the project financially.

References

1. van Griensven F, de Lind van Wijngaarden JW, Baral S, Grulich A. The global epidemic of HIV infection among men who have sex with men. Curr Opin HIV AIDS 2009; 4:300–307.

2. Baral S, Sifakis F, Cleghorn F, Beyrer C. Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: a systematic review. PLoS Med 2007; 4:e339.

3. The Commission on AIDS in Asia. Redefining AIDS in Asia. Crafting an effective response. New Delhi: The Commission on AIDS in Asia; 2008.

4. Heckathorn DD. Respondent-driven sampling: a new approach to the study of hidden populations. Soc Problems 1997; 44:174–199.

5. Malekinejad M, Johnston LG, Kendall C, Kerr LRFS, Rifkin MR, Rutherford GW. Using respondent-driven sampling methodology for HIV biological and behavioral surveillance in international settings: a systematic review. AIDS Behav 2008; 12:S105–S130.

6. Johnston LG, Malekinejad M, Kendall C, Iuppa IM, Rutherford GW. Implementation challenges to using respondent-driven sampling methodology for HIV biological and behavioral surveillance: field experiences in international settings. AIDS Behav 2008; 12:S131–S141.

7. Salganik MJ, Heckathorn DD. Sampling and estimation in hidden populations using respondent-driven sampling. Sociol Methodol 2004; 34:193–239.

8. Volz E, Heckathorn DD. Probability based estimation theory for respondent driven sampling. J Official Stat 2008; 24:79–97.

9. Wang J, Carlson RG, Falck RS, Siegal HA, Rahman A, Li L. Respondent-driven sampling to recruit MDMA users: a methodological assessment. Drug Alcohol Depend 2005; 78:147–157.

10. Frost SD, Brouwer KC, Firestone Cruz MA, Ramos R, Ramos ME, Lozada RM, et al. Respondent-driven sampling of injection drug users in two U.S.-Mexico border cities: recruitment dynamics and impact on estimates of HIV and syphilis prevalence. J Urban Health 2006; 83:i83–i97.

11. Heckathorn DD. Extensions of respondent-driven sampling: analyzing continuous variables and controlling for differential recruitment. Sociol Methodol 2007; 37:151–208.

Cited Here... | CrossRef

12. Ramirez-Valles J, Heckathorn DD, Vazquez R, Diaz RM, Campbell RT. From networks to populations: the development and application of respondent-driven sampling among IDUs and Latino gay men. AIDS Behav 2005; 9:387–402.

13. Mahajan AP, Sayles JN, Patel VA, Remien RH, Sawires SR, Ortiz DJ, et al. Stigma in the HIV/AIDS epidemic: a review of the literature and recommendations for the way forward. AIDS 2008; 22(Suppl 2):S67–S79.

14. Sullivan KM. Male self-disclosure of HIV-positive serostatus to sex partners: a review of the literature. J Assoc Nurses AIDS Care 2005; 16:33–47.

15. de Mello M, de Araujo Pinho A, Chinaglia M, Tun W, Barbosa Júnior A, Cristina FM, et al.Assessment of risk factors for HIV infection among men who have sex with men in the metropolitan area of Campinas city, Brazil, using respondent-driven sampling, Horizons Final Report. Washington, DC, USA: Population Council; 2008.

16. Choi KH, Ning Z, Gregorich SE, Pan QC. The influence of social and sexual networks in the spread of HIV and syphilis among men who have sex with men in Shanghai, China. J Acquir Immune Defic Syndr 2007; 45:77–84.

17. He Q, Wang Y, Lin P, Raymond HF, Li Y, Yang F, et al. High prevalence of risk behaviour concurrent with links to other high-risk populations: a potentially explosive HIV epidemic among men who have sex with men in Guangzhou, China. Sex Transm Infect 2009; 85:383–390.

18. Kajubi P, Kamya MR, Raymond HF, Chen S, Rutherford GW, Mandel JS, McFarland W. Gay and bisexual men in Kampala, Uganda. AIDS Behav 2008; 12:492–504.

19. Ma XY, Zhang QY, He X, Sun WD, Yue H, Chen S, et al. Trends in prevalence of HIV, syphilis, hepatitis C, hepatitis B, and sexual risk behavior among men who have sex with men: results of 3 consecutive respondent-driven sampling surveys in Beijing, 2004 through 2006. J Acquir Immune Defic Syndr 2007; 45:581–587.

20. Morris M, Kretzschmar M. Concurrent partnerships and the spread of HIV. AIDS 1997; 11:641–648.

Keywords:

epidemiology; HIV; men who have sex with men; respondent-driven sampling; risk behavior; sampling methods; surveillance

Interpretation of correlations in setpoint viral load in transmitting couples

AIDS:

23 October 2010 - Volume 24 - Issue 16 - p 2596–2597

doi: 10.1097/QAD.0b013e32833e7a64

Correspondence

Interpretation of correlations in setpoint viral load in transmitting couples

Fraser, Christophe; Hollingsworth, T Déirdre

Author Information

Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.

Received 13 July, 2010

Accepted 20 July, 2010

Correspondence to Professor Christophe Fraser, PhD, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. Tel: +44 20 7594 3397; e-mail: c.fraser@imperial.ac.uk

Two interesting reports studying correlations in HIV-1 setpoint viral loads (spVLs) and early viral loads within transmitting couples ^[1,2]were published recently, an observation which was foreshadowed in Zambia ^[3] and which we also recently showed in Uganda ^[4].

We wish to highlight that even weak correlation between spVL of individuals in transmitting couples can correspond to a large estimate for the role of viral genetic factors in determining spVL. Our difference in interpretation can be clarified by consideration of the sources of variance contributing to spVL (Fig. 1).

Fig. 1
Image Tools

The spVL of index and secondary cases within transmitting couples may be determined by a combination of factors related to the broadly similar viral genotype (viral factors), and other nonviral factors including host factors, coinfections, specificity and nature of immunological response or chance effects (Fig. 1a).

Nonviral factors affect the spVL of both index and the secondary cases in couples, explaining the difference between correlation between patients (Fig. 1b) and estimates of the strength of viral factors (Fig. 1a).

Hecht et al.^[1], van der Kuyl et al.^[2] and Tang et al.^[3] estimate the Pearson correlation coefficient, r, between spVL values of index cases and secondary cases in transmitting couples. We propose that if the aim is to infer the strength of viral factors on spVL, a better estimate can be obtained using analysis of variance (ANOVA) of within and between couple variance ^[4]. The coefficient of determination (R²) of the ANOVA is a lower-bound estimate for the proportion of variance in spVL explained by viral factors.

An additional benefit of ANOVA is that the analysis is easily adjusted for confounders such as sex of the host and viral subtype. A drawback is that the method is less transparent and requires extra adjustments for the parameters introduced into the model. In an idealized case wherein spVL values are normally distributed with identical variance, the estimates are related in a simple manner: the coefficient of determination (R²) of the ANOVA, as used in ^[4], is equal to the correlation coefficient (r), as used in ^[1–3]. Thus, the raw numbers are unchanged, but their interpretation in terms of the strength of viral effects in determining spVL is radically altered.

The unadjusted estimates for the proportion of variance in spVL explained by viral genotype in the four studies are 20% ^[3], 25% ^[2], 27% ^[4] and 55% ^[1]. These estimates are all higher than unadjusted estimates of 13% of variance in spVL explained by host genetic factors to date ^[5], although, of course, these latter estimates may increase as more host factors are discovered, and some host–virus interaction effects may be dually counted in individual analyses.

The additional observation that the relationship between spVL in transmitting pairs may depend on the stage of infection of the recipient^[2] (based on a small sample size) is plausible and interesting, and may aid the detailed elucidation of the mechanisms linking viral factors to spVL.

The four published studies together represent 250 couples, and the link in spVL within couples seems consistent and robust. Attributing variation in viral load to viral, host and interaction effects will undoubtedly shed light on the mechanisms of HIV pathogenesis. These results also support the hypothesis that spVL has evolved at the population level ^[6].

References

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