Hiv testing and counselling for women attending child health clinics: An opportunity for entry to prevent mother-to-child transmission and hiv treatment. Author

Although HIV has been shown to affect all domains of child functioning, motor development is the most apparent in terms of severity, early onset, and persistence across age groups. However, motor development has been the most widely assessed domain while language development has been less vigorously evaluated in SSA, hence an accurate quantitative estimate of the effect cannot yet be made.

Evidence for efficacy of male circumcision as an HIV prevention measure is increasing, but there is serious concern that men who are circumcised may subsequently adopt more risky sexual behaviors.

Using a prospective cohort study, we compared sexual behaviors of 324 recently circumcised and 324 uncircumcised men at 1, 3, 6, 9, and 12 months after circumcision/study enrollment. The main outcome indicators were incidence of sexual behaviors known to place men at increased risk of acquiring HIV, namely, having sex with partners other than their wife/wives for married men or other than "regular" girlfriends for unmarried men.

During the first month following circumcision, men were 63% and 61% less likely to report having 0 to 0.5 and >0.5 risky sex acts/week, respectively, than men who remained uncircumcised. This difference disappeared during the remainder of follow-up, with no excess of reported risky sex acts among circumcised men. Similar results were observed for risky unprotected sex acts, number of risky sex partners, and condom use.

During the first year post-circumcision, men did not engage in more risky sexual behaviors than uncircumcised men, suggesting that any protective effect of male circumcision on HIV acquisition is unlikely to be offset by an adverse behavioral impact.

Engelson, E. S.

Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART).

The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women.

Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (S(I)) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n=17) and in obese healthy controls (n=32).

The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P<0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with S(I) (P<0.001 for the regression's slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with S(I) did not differ significantly between groups. For both groups combined, the best model predicting a low S(I) included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r(2)=0.44, P=0.0003).

In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance.

To review recent research findings on the specific expression of endogenous retroviral sequences (ERVS) in reproductive tissues and their possible physiological roles. ERVS have been implicated in several biological events such as induction of resistance to exogenous retrovirus invasion, involvement in placental trophoblast formation, sperm maturation and differentiation; and stimulation of local immunosuppression to protect the foetus from immunological attack.

Critical review of relevant articles and abstracts cited in international and local journals, literature searches on Medline and Medchem up to 2005.

Retroviruses have been implicated in the induction of tumour and immunological disorders. Over the years, endogenous retroviruses (ERVs) and retroviral elements have been detected in the genome of many vertebrate species, including primates. The evidence for the presence of retroviruses in the primate tissues such as the placenta, ovary, breast, testis and epididymis has been documented using electron microscopic studies. Retrovirus-like particles were found budding from the basal membrane of syncytiotrophoblasts, as well as in tumour cell lines in embryonic carcinoma or teratocarcinomas. Apart from their pathological effects, recent evidence suggests that these ERVs may play useful roles in normal physiological events.

Recent studies indicate the expression of endogenous retroviruses in the testis, epididymis, placenta and breast. However, limited data exist on the detection of ERVs in the ovary. Overall, the precise functions for ERVs in these tissues are not well understood. In the testis and epididymis, speculative functions may include among others spermatogenesis and/or sperm maturation (differentiation) whereas in placenta they are possibly associated with trophoblast fusion and locally induced immunosuppression to protect the foetus from immunological attack. Experiments in our laboratory have indicated restricted expression of retroviral antigens including baboon endogenous retroviral proteins (BERV), ERV-3, HIV-1 gp41 and HERV-K env in the baboon ovary.

ERVs are specifically expressed in different mammalian reproductive tissues and may have unique physiological roles.

To explore behaviour change, baseline risk behaviour, perception of risk, HIV disclosure and life events in health centre-based voluntary counselling and testing (VCT) clients.

Single-arm prospective cohort with before-after design at three (one urban and two rural) government health centres in Kenya; study duration 2 years, 1999-2001.

Numbers of sexual partners, partner type, condom use, reported symptoms of sexually transmitted infection, HIV disclosure and life events.

High rates of enrollment and follow-up provided a demographically representative sample of 401 clients with mean time to follow-up of 7.5 months. Baseline indicators showed that clients were at higher risk than the general population, but reported a poor perception of risk. Clients with multiple partners showed a significant reduction of sexual partners at follow-up (16% to 6%; p<0.001), and numbers reporting symptoms of sexually transmitted infection decreased significantly also (from 40% to 15%; p<0.001). Condom use improved from a low baseline. Low rates of disclosure (55%) were reported by HIV-positive clients. Overall, no changes in rates of life events were seen.

This study suggests that significant prevention gains can be recorded in clients receiving health centre-based VCT services in Africa. Prevention issues should be considered when refining counselling and testing policies for expanding treatment programmes.

Although breast-feeding accounts for 15-20% of mother-to-child transmission (MTCT) of HIV, it is not prohibited in some developing countries because of the higher mortality associated with not breast-feeding. We assessed the potential impact, on HIV infection and infant mortality, of a recommendation for shorter durations of exclusive breast-feeding (EBF) and poor compliance to these recommendations.

We developed a deterministic mathematical model using primarily parameters from published studies conducted in Uganda or Kenya and took into account non-compliance resulting in mixed-feeding practices. Outcomes included the number of children HIV-infected and/or dead (cumulative mortality) at 2 years following each of 6 scenarios of infant-feeding recommendations in children born to HIV-infected women: Exclusive replacement-feeding (ERF) with 100% compliance, EBF for 6 months with 100% compliance, EBF for 4 months with 100% compliance, ERF with 70% compliance, EBF for 6 months with 85% compliance, EBF for 4 months with 85% compliance.

In the base model, reducing the duration of EBF from 6 to 4 months reduced HIV infection by 11.8% while increasing mortality by 0.4%. Mixed-feeding in 15% of the infants increased HIV infection and mortality respectively by 2.1% and 0.5% when EBF for 6 months was recommended; and by 1.7% and 0.3% when EBF for 4 months was recommended. In sensitivity analysis, recommending EBF resulted in the least cumulative mortality when the a) mortality in replacement-fed infants was greater than 50 per 1000 person-years, b) rate of infection in exclusively breast-fed infants was less than 2 per 1000 breast-fed infants per week, c) rate of progression from HIV to AIDS was less than 15 per 1000 infected infants per week, or d) mortality due to HIV/AIDS was less than 200 per 1000 infants with HIV/AIDS per year.

Recommending shorter durations of breast-feeding in infants born to HIV-infected women in these settings may substantially reduce infant HIV infection but not mortality. When EBF for shorter durations is recommended, lower mortality could be achieved by a simultaneous reduction in the rate of progression from HIV to AIDS and or HIV/AIDS mortality, achievable by the use of HAART in infants.

Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive.

To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population.

Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases.

Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82).

In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus

A lack of male circumcision has been associated with increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition in a number of studies, but questions remain as to whether confounding by behavioral practices explains these results. The objective of the present study was to model per-sex act probabilities of female-to-male HIV-1 transmission (i.e., infectivity) for circumcised and uncircumcised men, by use of detailed accounts of sexual behavior in a population with multiple partnerships.

Data were collected as part of a prospective cohort study of HIV-1 acquisition among 745 Kenyan truck drivers. Sexual behavior with wives, casual partners, and prostitutes was recorded at quarterly follow-up visits. Published HIV-1 seroprevalence estimates among Kenyan women were used to model HIV-1 per-sex act transmission probabilities.

The overall probability of HIV-1 acquisition per sex act was 0.0063 (95% confidence interval, 0.0035-0.0091). Female-to-male infectivity was significantly higher for uncircumcised men than for circumcised men (0.0128 vs. 0.0051; P=.04). The effect of circumcision was robust in subgroup analyses and across a wide range of HIV-1 prevalence estimates for sex partners.

After accounting for sexual behavior, we found that uncircumcised men were at a >2-fold increased risk of acquiring HIV-1 per sex act, compared with circumcised men. Moreover, female-to-male infectivity of HIV-1 in the context of multiple partnerships may be considerably higher than that estimated from studies of HIV-1-serodiscordant couples. These results may explain the rapid spread of the HIV-1 epidemic in settings, found throughout much of Africa, in which multiple partnerships and a lack of male circumcision are common.

To determine the correlation between polymorphisms in the IL-4 gene cluster and resistance to HIV-1 infection.

A cross-sectional genetic analysis of polymorphisms within the IL-4 gene cluster was conducted in a well-described female sex worker cohort from Nairobi, Kenya, known to exhibit differential susceptibility to HIV-1 infection.

Microsatellite genotyping was used to screen six microsatellite markers in the IL-4 gene cluster for associations with HIV-1 resistance. Further analysis of the interferon regulatory factor 1 (IRF-1) gene was conducted by genomic sequencing. Associations between IRF-1 gene polymorphisms and the HIV-1 resistance phenotype were determined using the chi-square test and Kaplan-Meier survival analysis. The functional consequence of IRF-1 polymorphism was conducted by quantitative Western blot.