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Archive for February 26th, 2012

Just how infectious is HIV?

26 Feb, 12 | by Leslie Goode, Blogmaster

Can we put a figure on the infectivity of HIV infection per coital act, and on the relative importance of the various determinants of transmission?

Estimates are needed in order to plan effective interventions.  A recent paper, published in the Journal of Infectious Diseases (Hughes, Celum et al.), discussed by an editorial (Gray & Wawer) of the same issue, represents the latest attempt at estimating infectivity and its determinants for sub-Saharan Africa.  The study was conducted on the back of a large randomized trial of HSV-2 suppression for prevention of HIV transmission between sero-discordant couples, and involved 3,293 couples at 14 sites in S and E Africa over a period of 24 months.

First the figures.  Transmission per coital act was estimated at 0.0019 for male-to-female, and 0.001 for female-to-male.  The major driver of transmission was HIV load in the infected partner: each log10 increment in viral load produced a 2.9 fold adjusted risk of transmission.  Condom use reduced risk by 82%.

On the whole, these findings provide reassuring corroboration of the findings of earlier, smaller studies.  The figure for overall infectivity is similar to that reported during the latent stage of HIV infection in low-income countries.  Such a figure does not explain the rapid spread of the infection in many sub-Saharan settings – because, as Gray and Wawer point out, a study of this kind, involving stable sero-discordant couples, is unable to factor in the vastly higher levels of infectivity associated with early and late stage disease.

The figure of 2.9 for the multiplication of risk with log10 viral load increment is higher than prior estimates, and may reflect more precise estimates enabled in this study by quarterly viral load measurements (Lingappa, Hughes, Wang et al.).

Numerous earlier attempts to establish HIV infectivity and its determinants are surveyed in a recent meta-analysis (Boily, Baggaley and Wang et al.).  Two things distinguish the present paper.  The first is sheer scale:  at 3,293 couples, the number of recruits exceeds considerably that of the next largest study (Fideli, Aldrovandi et al.), and far exceeds participation in previous studies (generally placed at  <200 participant couples).  The size of a study like this is an important factor because it enhances its ability to reliably estimate co-factors of transmission.  The second distinguishing feature is the seriousness of the effort to estimate the number of sexual events:  participant couples were interviewed about their sexual activity every month – a frequency that greatly exceeds the frequency of interviews in comparable studies.  These factors, along with frequency of quarterly viral load measurements, seem to mark a considerable gain in reliability, as against earlier attempts to place a figure on latent HIV infectivity.

James P. Hughes, Connie Celum et al., “Determinants of Per-Coital-Act HIV-1 Infectivity Among African HIV-1- Serodiscordant Couples”, Journal of Infectious Diseases 205:3, January 2012

Ronald H. Gray and Maria J. Wawer, “Probability of Heterosexual HIV-1 Transmission per Coital Act in Sub-Saharan Africa” (Editorial), Journal of infectious Diseases 205:3, January 2012

J. R. Lingappa, J.P. Hughes, R.S. Wang et al., “Estimating the impact of plasma HIV-1 RNA reductions on herosexual HIV-1 transmission risk”, PLoS One 2010,10.1371/journal.pone.0012598

M. C. Boily, R.F. Baggaley, L. Wang et al. “Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies, Lancet Infectious Diseases 2009; vol. 9, no.2, Feb. 2009

U. S. Fideli, S. A. Allen, R. Musonda et al., “Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa”, AIDS Res Hum Retroviruses 2001; 17 (10): 901-10

Cervical cancer prevention in low-resource settings: could self-testing be the answer?

26 Feb, 12 | by Leslie Goode, Blogmaster

A recent paper (Qiao et al.) – Journal of National Cancer Institute (JNCI) 104:3 – reports the findings of a series of 5 population-based studies of self-screening for cervical cancer in rural China, involving 13,140 participants.  They are particularly relevant to STI readers on account of issues they raise about the effectiveness of screening programs in low-resource settings.  An editorial in the same issue of JNCI (Patrick Petignat) provides an interesting discussion of these issues.

While a seventh of the world’s cases of cervical cancer (the third most common type of cancer in women) occur in China, a high proportion of these will be in low-resource rural settings where access to healthcare is very limited, and the kind of screening (smear or pap test) conducted in developed countries is not feasible.  The last few years have seen the development of a promising alternative to the smear test, which involves screening for the strains of Human Papilloma Virus (HPV) that can lead to cervical cancer (HPV DNA).  So far as low-resource settings are concerned, the latter test has the notable advantage that it can be administered by patients on themselves, and need not require significant medical resources and laboratory infrastructure.

Could self-administered HPV DNA testing provide a practicable mode of screening in areas, like rural, China where trained medical practitioners are scarce?              Petignat, in his JNCI editorial, helpfully distinguishes between the issue of diagnostic performance, and the wider issue of the likely efficacy of self-testing interventions outside the research setting.

The paper (Qiao et al.) addresses the first issue.  Participants in the five studies were all tested with HPV DNA administered by physician and with self-administered HPV DNA, as well as with  two other tests – liquid-based cytology (LBC) and visual inspection with acetic acid (VIA) (a test that has been proposed for low-resource settings).   Sensitivity and specificity of self-administered HPV DNA in detecting biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) proved to be 86.2% and 80.07% respectively as against 97% and 82.7% for HPV DNA performed by physician.  Sensitivity of self-administered HPV DNA at 86.2% was actually superior to sensitivity of LBC at 80.7% and VIA at 50.3%. So far so good.  The real problem with HPV DNA, whether self-administered or administered by physician, proved to be its relatively low specificity of 80.7%.  Without further triage, screening with HPV DNA would result in an altogether unfeasible 15.6% of women being referred for colposcopy.  A combination of self-HPV with triage using LBC or VIA might offer the most feasible solution.  Computer models for the impact of these combinations were developed in the course of the study, and produced levels of referral for colposcopy of 4.8% and 4.5% respectively.  Given LBC requires laboratory facilities and a medical infrastructure not likely to be achievable in a low-resource context, self-HPV combined with VIA comes out as the most feasible option.

There remains, however, the issue of the likely feasibility of self-testing interventions outside the research setting. The authors comment on the willingness of participants (70% of those invited) and the almost 100% compliance of participants with instructions.  This is promising. But compliance on the part of volunteer participants is one thing: likely take-up of self-testing interventions outside such a framework is quite another, and would no doubt depend on the delivery of the intervention, as well as on a range of cultural factors.  The authors refer to a relatively inexpensive testing kit – care HPV.  Ultimately, however, cost-effectiveness will depend on take-up.  Petignat concludes with a salutary note of warning: “Self-HPV per se is only a part of a secondary prevention program, and obstacles to program participation might not only result in program failure but also be harmful for women”.  In view of this, further research seems called for.

Fang-Hui Zhao, You-Lin Qiao et al., “Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method”, Journal of the National Cancer Institute, 104:3, 8th Feb., 2012

Patrick Petignat, Pierre Vassilakos, “Is It Time to Introduce HPV Self-Sampling for Primary Cervical Cancer Screening?” (Editorial) Journal of the National Cancer Institute, 104:3, 8th Feb., 2012

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