Source of new infections in generalised HIV epidemics – Authors' reply

Correspondence

heterosexual transmission between individuals who are not in stable couples.) We cannot assess whether Dunkle and colleagues’ anomalous finding results from violations of the model assumptions or problems with the Demographic and Health Survey data used. We declare that we have no conflict of interest.

*Stan Becker, Ron Gray [email protected] Johns Hopkins University, Department of Population, Family and Reproductive Health, 615 North Wolfe Street, Baltimore, MD 21205, USA 1

Dunkle KL, Stephenson R, Karita E, et al. New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet 2008; 371: 2183–91.

Authors’ reply In our paper, we concluded that (1) most new HIV infections in urban Zambia and Rwanda are acquired from cohabiting partners, and (2) many infections could be prevented with couples’ HIV counselling and testing (CVCT). Transmission of 20% per year is consistent with two contacts per week and a per-contact transmission risk of 1 in 500; nonetheless, we acknowledge James Shelton and David Stanton’s point that, without direct observational data, this “without counselling” seroincidence is debatable. Changing this rate, however, has no effect on the estimate of new infections acquired from

spouses (p 2187 and table 5). It affects the estimated effect of CVCT. However, we respectfully disagree that 5–10% is a valid baseline value. Seroincidence in discordant couples from the extensively counselled Rakai cohort was 11·8 per 100 person-years.1 Matovu2 concludes that individual VCT in Rakai does not result in decreased risk and we agree that condom use is rare among HIV-negative adults who are unaware that their spouse is HIV-positive.3 Unfortunately, neither Matovu nor Quinn report how many couples in their cohort knew each other’s serostatus, and this uncertainty is common to the other cohorts reviewed by Guthrie.4 As a middle ground, we offer the proportion of infections preventable by CVCT comparing 20% with lower baseline rates of 12% for Rwanda and 15% for Zambia (table). The effect of CVCT remains substantial. We do not account for propagated spread of highly infectious new infections—ie, we underestimate serodiscordance in both non-cohabiting and cohabiting couples. If both quantities are underestimated, the effect on the proportion of infections attributable to cohabiting couples is minimal (table 6). The pie chart showing a high proportion of discordant couples represents a snapshot of a dynamic process in which discordant couples transmit, die, or split up, and are replaced by new discordant

Reduction in HIV transmission among serodiscordant cohabiting couples via CVCT Kigali, Rwanda 20% to 3%

Lusaka, Zambia 12% to 3%*

20% to 7%

15% to 7%†

Proportion of new heterosexual infections prevented among: All sexually active men

79·7%

70·0%

37·2%

30·6%

We declare that we have no conflict of interest.

Married men

83·9%

74·0%

54·3%

44·6%

All sexually active women

79·1%

70·3%

50·9%

42·9%

Married women

84·5%

74·6%

62·5%

52·7%

*Kristin L Dunkle, Lauren Greenberg, Aaron Lanterman, Rob Stephenson, Susan Allen

*3% is the observed seroincidence in discordant couples receiving CVCT at our Kigali site. †7% is the observed seroincidence in discordant couples receiving CVCT at our Lusaka site.

Table: Varying potential effect of couples’ HIV counselling and testing (CVCT) in different sites based on different assumptions about baseline transmission of HIV over a 12-month period

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couples resulting from premarital or extramarital contact. The “steady state” has a large proportion of couples discordant at any given time. This brings up a related point about our model: our estimate of the benefit of couples’ counselling does not account for reduced HIV incidence in couples who test concordantly HIV-negative. Among 509 such couples in Kigali, Rwanda, four individuals acquired HIV in 1 year (0·4 per 100 person-years), only one of whom transmitted it to their spouse.5 This very low incidence affirms the beneficial effect of CVCT, confirming that couples’ testing— rather than the current standard of care stressing individual VCT—is essential to future HIV prevention efforts. Ron Gray and Stan Becker are not the first to assert that the proportion of HIV infections attributable to married or cohabiting couples must be capped at 50%. This is false. Such a cap would only apply if one looked retrospectively at the source of existing infections (see the third paragraph of our Discussion). This was not the research question we addressed. We took the population-based relationship structures as defined in the Demographic and Health Survey data and linked this to observed rates of serodiscordance to create a 12-month forward projection based on straightforward probability calculations. The cap for coupleattributable infections in this type of analysis, which encapsulates all past events in the baseline set-up and projects forward, is 100%. We respectfully suggest that ours is the more relevant question for setting policy and allocating resources to prevent future infections.

[email protected] Behavioral Sciences and Health Education (KLD), Rwanda Zambia HIV Research Group (LG, SA), and Hubert Department of Global Health (RS), Rollins School of Public Health, Emory University,

www.thelancet.com Vol 372 October 11, 2008

Correspondence

1520 Clifton Road NE, Atlanta, GA 30322, USA (AL); and School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA (AL) 1

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Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of Human Immunodeficiency Virus Type 1. N Engl J Med 2000; 342: 921–29. Matovu JKB, Gray RH, Makumbi F, et al. Voluntary HIV counseling and testing acceptance, sexual risk behavior and HIV incidence in Rakai, Uganda. AIDS 2005; 19: 503–11. Allen S, SerufiliraA, Bogaerts J, et al. Confidential HIV Testing and Condom Promotion in Africa. JAMA 1992; 268: 3338–43. Guthrie B, de Bruyn G, Farquhar C. HIV-1 discordant couples in sub-Saharan Africa: explanations and implications for high rates of discordancy. Curr HIV Res 2007; 5: 416–29. Roth DL, Stewart KE, Clay OJ, van der Straten A, Karita E, Allen S. Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counseling programme for men. Int J STD AIDS 2001; 12: 181–88.

Should prednisolone be first-line therapy for acute gout? Hein Janssens and colleagues (May 31, p 1854)1 are to be commended for their randomised trial that showed prednisolone to be as effective as naproxen for the treatment of acute gout. Janssens and colleagues suggest that corticosteroids might be a safer approach than colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) and conclude that their results provide a strong argument to consider prednisolone as a first treatment option in patients with gout. This latter assertion requires some comments. Well known adverse effects of glucocorticoids include hypertension and diabetes mellitus; these are frequent disorders in patients with gout.2 These adverse events can occur even in the short term on low-dose therapy and seem to be dose-dependent. In patients with impaired glucose tolerance, a rapid increase in plasma glucose can be seen with glucocorticoids and the diabetogenic effects can be lengthy. It would have been interesting if Janssens and colleagues compared www.thelancet.com Vol 372 October 11, 2008

diastolic blood pressure and glucose concentrations at the end of the 5-day treatment course in both groups. Clinical experience has taught us that oral corticosteroids for gout expose patients to the risk of rebound attacks and possible drug dependency. Additionally, experimental data suggest that steroid treatment could favour tophus formation,3 as frequently seen in patients with transplant gout. Colchicine is an effective treatment for acute gout and is recommended as a first-line therapy.4 Gastrointestinal symptoms are common but uncontrolled reports suggest that use of low doses of colchicine (1·5 mg daily or less) might be effective and better tolerated.5 Corticosteroids are probably a reasonable choice for patients in whom colchicine or NSAIDs are contraindicated. We declare that we have no conflict of interest.

*Pascal Richette, Thomas Bardin [email protected] Hopital Lariboisière, 75010 Paris, France 1

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Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008; 371: 1854–60. Rott KT, Agudelo CA. Gout. JAMA 2003; 289: 2857–60. Rull M, Clayburne G, Sieck M, Schumacher HR. Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch. Rheumatology 2003; 42: 1093–100. Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65: 1312–24. Morris I, Varughese G, Mattingly P. Colchicine in acute gout. BMJ 2003; 327: 1275–76.

Authors’ reply In responding to Pascal Richette and Thomas Bardin, we would like to specify the benefit/risk ratio of systemic corticosteroids in the treatment of gout arthritis. This ratio depends on the balance of therapeutic and adverse effects with regard to patient-related factors. For gout arthritis, non-steroidal anti-

inflammatory drugs (NSAIDs) and colchicine are effective, but they have many cardiovascular and gastrointestinal adverse effects, and patients with gout often have comorbidities that contraindicate these drugs. Gout patients present most often in primary care with a sudden and very painful arthritis, and expect quick relief. At that moment, doctors might not be aware of the patient’s comorbidity status (such as latent heart failure, use of anticoagulants, or renal insufficiency). Therefore drugs with an appropriate benefit/risk ratio are needed. We propose prednisolone, 35 mg once per day, for 5 days. If used that way there is hardly any evidence of important side-effects. In reference to the management of acute exacerbations of chronic obstructive pulmonary disease and other similar disorders with systemic corticosteroids, important adverse effects such as diabetes mellitus or hypertension are uncommon even when these drugs are used in high doses (30–100 mg/day) or very high doses (>100 mg/day) and for as many as 21 days.1,2 Furthermore, the primarycare prevalence of diabetes mellitus in gout patients is low,3,4 and similar to the rate in individuals without gout.3 Although we were aware of the hypothetical risk of rebound attacks, we found only textbooks as references for this. Neither in our trial, nor in other gout trials on systemic corticosteroids, were rebound attacks reported.5 Additionally, it is not appropriate to assess rebound attacks in gout trials because recurrent attacks are part of the disease. Corticosteroid-drug dependency cannot be an important clinical problem because uratelowering therapy is recommended when a patient has had more than three to five attacks a year. Richette and Bardin’s concern about a higher risk of tophus formation is solely based on an experimental study on depot corticosteroids in a rat air pouch model. 1301