HIV This Week

Causes of acute hospitalization in adolescence: burden and spectrum of HIV-related morbidity in a country with an early-onset and severe HIV epidemic: a prospective survey.

Ferrand RA, Bandason T, Musvaire P, Larke N, Nathoo K, Mujuru H, Ndhlovu CE, Munyati S, Cowan FM, Gibb DM, Corbett EL. PLoS Med. 2010;7:e1000178.

Survival to older childhood with untreated, vertically acquired HIV infection, which was previously considered extremely unusual, is increasingly well described. However, the overall impact on adolescent health in settings with high HIV seroprevalence has not previously been investigated. In this study adolescents (aged 10-18 y) systematically recruited from acute admissions to the two public hospitals in Harare, Zimbabwe, answered a questionnaire and underwent standard investigations including HIV testing, with consent. Pre-set case-definitions defined cause of admission and underlying chronic conditions. Participation was 94%. 139 (46%) of 301 participants were HIV-positive (median age of diagnosis 12 y: interquartile range [IQR] 11-14 y), median CD4 count = 151; IQR 57-328 cells/microl), but only four (1.3%) were herpes simplex virus-2 (HSV-2) positive. Age (median 13 y: IQR 11-16 y) and sex (57% male) did not differ by HIV status, but HIV-infected participants were significantly more likely to be stunted (z-score<-2: 52% versus 23%, p<0.001), have pubertal delay (15% versus 2%, p<0.001), and be maternal orphans or have an HIV-infected mother (73% versus 17%, p<0.001). 69% of HIV-positive and 19% of HIV-negative admissions were for infections, most commonly tuberculosis and pneumonia. 84 (28%) participants had underlying heart, lung, or other chronic diseases. Case fatality rates were significantly higher for HIV-related admissions (22% versus 7%, p<0.001), and significantly associated with advanced HIV, pubertal immaturity, and chronic conditions. HIV is the commonest cause of adolescent hospitalisation in Harare, mainly due to adult-spectrum opportunistic infections plus a high burden of chronic complications of paediatric HIV. Low HSV-2 prevalence and high maternal orphanhood rates provide further evidence of long-term survival following mother-to-child transmission. Better recognition of this growing phenomenon is needed to promote earlier HIV diagnosis and care.

For full text access click here:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000178

Editor’s note: Zimbabwe, a few years ahead of other countries in the region, may be the proverbial ‘canary in the mine’, alerting us to what will become increasingly evident – the unrecognised numbers of adolescents with HIV infection who were infected through mother-to-child (vertical) transmission. Adolescents (10 to 18 years) get lost in our epidemiological and clinical categories of <15 years and 15 to 49 years. Adolescents also get lost in our service provision, with freestanding services and youth-friendly clinics for adolescents rare in many settings. Legal barriers may prevent young people from learning their HIV status without guardian consent. Provider-initiated HIV testing and counselling offered to all adolescents in high HIV prevalence countries would go a long way to overcoming late diagnosis (the median age is 11 to 12 years), delayed antiretroviral treatment, blunted growth, and slow pubertal development. But to really make a difference in their growth, health, and survival, adolescents with HIV infection shouldn’t have to wait until they are sick to find out they have HIV. There is no time to lose – a considerable epidemic of long time survivors of vertical transmission is expected during the coming decade and strategic planning must start now or speed up rapidly. The later the diagnosis is made, the higher is the mortality.

Does it fit okay? Problems with condom use as a function of self-reported poor fit.

Crosby RA, Yarber WL, Graham CA, Sanders SA. Sex Transm Infect. 2010;86:36-8.

The study was set up to identify associations between men's self-reports of ill-fitting condoms and selected condom use problems, using an event-specific analysis. A convenience sample of men was recruited via advertisements in newspapers (two urban and one small town) and a blog on the website of a condom sales company. Men completed a questionnaire posted on the website of The Kinsey Institute for Research in Sex, Gender, and Reproduction. Inclusion criteria were: at least 18 years old, used condoms for penile-vaginal intercourse in the past 3 months and the ability to read English. In controlled, event-specific, analyses of 436 men, those reporting ill-fitting condoms (44.7%) were significantly more likely to report breakage (adjusted odds ratio (AOR 2.6), slippage (AOR 2.7), difficulty reaching orgasm, both for their female partners (AOR 1.9) and for themselves (AOR 2.3). In addition, they were more likely to report irritation of the penis (AOR 5.0) and reduced sexual pleasure, both for their female partner (AOR 1.6) and for themselves (AOR 2.4). Furthermore, they were more likely to report that condoms interfered with erection (AOR 2.0), caused erection loss (AOR 2.3), or became dry during sex (AOR 1.9). Finally, they were more likely to report removing condoms before penile-vaginal sex ended (AOR 2.0). Men and their female sex partners may benefit from public health efforts designed to promote the improved fit of condoms.

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/20157178

Editors’ note: Given that condoms are widely used to prevent pregnancy and that correct and consistent condom use is the cornerstone of HIV prevention for sexually active people, it is amazing that more research on the effects of ill-fitting condoms on penile erection, sexual pleasure, and discontinuation before the end of the sex act has not been done. This convenience sample of men from 28 countries (74% living in the US) defined ‘ill-fitting’ as ‘too long or too short’ and/or too narrow or too wide’. Almost 45% of men reporting ill-fitting condom use at the last sex act. It is not clear whether the problem is with the product itself or how it is applied. No wonder condoms get bad press! Much more work is needed to find out how this problem can be rectified – too many lives depend upon correct and consistent condom use.

Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study.

Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. PLoS Med. 2010;7:e1000229.

With the rapid expansion of antiretroviral therapy services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether antiretroviral therapy initiation influences pregnancy rates. The authors analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment programme for women, children, and families. From 11 programmes in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; antiretroviral therapy was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving antiretroviral therapy (9.0/100 PY) compared to women not on antiretroviral therapy (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19-2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts. Antiretroviral therapy use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioural or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services.

For full text access click here:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000229

Editors’ note:  Although the incidence of pregnancy ranged 5-fold across these seven countries, the association between antiretroviral therapy and pregnancy was consistent across countries. Within 4 years of starting on treatment, one-third of women became pregnant, constituting an almost 80% increased incidence over women who were not yet eligible for antiretroviral therapy. There is no doubt that antiretroviral therapy can improve well-being, increase sexual activity, and lead to renewed fertility intentions through increased hope and planning for the future. However, 30% of pregnancies in sub-Saharan Africa, regardless of HIV status, are unintentional. This multi-country, women-centred, family-focused care and treatment initiative surprisingly did not include standardised counselling on pregnancy and contraceptive use, although barrier and non-barrier contraceptive methods were provided on site or by referral, and did not explore fertility desires and pregnancy plans. As a result, options for fertility planning were not systematically discussed with women, treatment regimens were not adjusted to reduce the impact of nevirapine on hormonal contraceptive blood levels for those women who chose this method of contraception, and the opportunity to help women shape their own futures and that of their families appears to have been missed. This study provides strong justification for the integration of family planning services into antiretroviral therapy programmes.

Targeting early infection to prevent HIV-1 mucosal transmission.

Haase AT. Nature. 2010;464:217-23.

Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/20220840

Editors’ note: Sexual mucosal transmission of HIV is the most common mode of acquisition. This excellent review of what we know now about the events from mucosal exposure to established systemic infection sets out the clear challenges before us and describes the window of opportunity that the earliest stage of infection presents. With vaginal transmission probabilities estimated at 1 in 100 to 1 in 1000, HIV can have a difficult time getting a toehold. Although people with HIV infection generally have several genetically distinct HIV viruses, surprisingly, due to what is called a ‘genetic bottleneck’, only one virus or infected cell initiates productive infection in almost 80% of people who become infected, with the remaining 20% becoming infected with two to five viruses. After exposure, prevention has to start by stopping the establishment of this small founder population in the first week of infection, taking advantage of its vulnerability to reduce its basic reproductive rate below 1. There are only a few days before dissemination and establishment of systemic infection in the second week with massive depletion of memory CD4 T cells in the gut and immune activation providing a new supply of target cells for HIV. Understanding what happens in early infection may not only help explain why male circumcision partially protects heterosexual men and how modest protection occurred in the Thai RV144 vaccine trial, it will lead to the design of targeted biomedical strategies that prevent establishment of HIV infection when HIV exposure occurs at mucosal surfaces.