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



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Conclusion:

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.



Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa.
Author: Abu-Raddad, L. J.; Patnaik, P., and Kublin, J. G.
Source: Science. 2006 Dec 8; 314(5805):1603-6.
Abstract: Mounting evidence has revealed pathological interactions between HIV and malaria in dually infected patients, but the public health implications of the interplay have remained unclear. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes; in addition, susceptibility to malaria is enhanced in HIV-infected patients. A mathematical model applied to a setting in Kenya with an adult population of roughly 200,000 estimated that, since 1980, the disease interaction may have been responsible for 8,500 excess HIV infections and 980,000 excess malaria episodes. Co-infection might also have facilitated the geographic expansion of malaria in areas where HIV prevalence is high. Hence, transient and repeated increases in HIV viral load resulting from recurrent co-infection with malaria may be an important factor in promoting the spread of HIV in sub-Saharan Africa.

Male circumcision in Siaya and Bondo Districts, Kenya: prospective cohort study to assess behavioral disinhibition following circumcision.
Author: Agot, K. E.; Kiarie, J. N.; Nguyen, H. Q.; Odhiambo, J. O.; Onyango, T. M., and Weiss, N. S.
Source: J Acquir Immune Defic Syndr. 2007 Jan 1; 44(1):66-70.
Abstract: Background:

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.


Methods:

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.


Results:

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.


Discussion:

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.




HLA and T in cross-reactive immune responses to HIV-1 subtype A, CRF01_AE and CRF02_AG cell elements vaccine sequence in Ivorian blood donors. Vaccine.
Author: Aidoo, M.; Sawadogo, S.; Bile, E. C.; Yang, C.; Nkengasong, J. N., and McNicholl, J. M.
Abstract: Comprehensive understanding of the determinants of cross-subtype immune responses in HIV infection is critical to developing efficacious HIV vaccines against multiple viral subtypes. Because HIV-1 subtype A or recombinants comprising subtype A are prevalent in Africa and parts of Asia where HIV is spreading, we assessed the determinants of cross-subtype immune responses in HIV-infected blood donors from Cote d'Ivoire to peptides from a candidate CRF02_AG vaccine sequence, a subtype A sequence from western Kenya and a CRF01_AE sequence from Thailand. We present evidence that immune recognition of multiple viral subtypes is maintained by recognition of multiple epitopes. Our data suggest that complete escape of HIV from immune recognition is uncommon. Evaluation of these frequently generated cross-reactive responses should be included in immunogenicity trials of HIV vaccines.

Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV- infected women.
Author: J. B.; Kenya, S.; He, Q.; Wainwright, M.; Berk, E. S.; Heshka, S.; Kotler, D. P., and

Engelson, E. S.


Source: Am J Clin Nutr. 2007 Jul; 86(1):100-6.
Abstract: Background:

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


Objective:

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


Design:

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).


Results:

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).


Conclusion:

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



Characterization of CD8 T-cell responses in HIV-1-exposed seronegative commercial sex workers from Nairobi, Kenya.
Author: Alimonti, J. B.; Kimani, J.; Matu, L.; Wachihi, C.; Kaul, R.; Plummer, F. A., and Fowke, K. R.
Source: Immunol Cell Biol. 2006 Oct; 84(5):482-5.
Abstract: CD8+ T-lymphocyte responses are crucial to the control of HIV-1; therefore, studying the CD8+ immune response in a naturally resistant population could provide valuable insights into an effective anti-HIV response in healthy uninfected individuals. Approximately 5-10% of the women in the Pumwani Commercial Sex Worker cohort in Nairobi, Kenya, have been highly exposed to HIV-1 yet remain HIV-IgG-seronegative and HIV-PCR negative (HIV(ES)). As IFN-gamma production correlates to cytotoxic function, the CD8+ T-lymphocyte IFN-gamma response to HIV p24 peptides was compared in HIV(ES) and HIV-infected (HIV+) individuals. Almost 40% of the HIV(ES) had a CD8+ IFN-gamma+ response that was five times lower in magnitude than that of the HIV+ group. The breadth of the response in HIV(ES) was very narrow and focused primarily on one peptide that is similar to the protective KK10 peptide. In the HIV+ group, low peripheral CD4+ counts negatively influenced the number of CD8+ cells producing IFN-gamma, which may undermine the ability to control HIV. Overall, many of the HIV(ES) women possess a HIV-1 p24-specific CD8+ IFN-gamma response, providing evidence to the specificity needed for an effective HIV vaccine

CD4+ T cell responses in HIV-exposed seronegative women are qualitatively distinct from those in HIV-infected women.
Author: Alimonti, J. B.; Koesters, S. A.; Kimani, J.; Matu, L.; Wachihi, C.; Plummer, F. A., and Fowke, K. R.
Source: J Infect Dis. 2005 Jan 1; 191(1):20-4.
Abstract: The immune response of human immunodeficiency virus (HIV)-exposed seronegative (ESN) women may be qualitatively different from that in those infected with HIV (HIV(+)). In a cohort of female commercial sex workers in Nairobi, Kenya, we found significantly lower (P< or =.01) levels of CD4(+)-specific immune activation and apoptosis in the ESN women compared with those in the HIV(+) women. Compared with the HIV(+) women, a lower proportion of the ESN women showed p24 peptide pool responses by the short-term, CD4(+)-specific, interferon (IFN)- gamma intracellular cytokine staining assay, whereas the proportion showing responses by the long-term, CD8(+)-depleted T cell proliferation assay was similar. Interestingly, the ESN responders had a 4.5-fold stronger proliferation response (P=.002) than the HIV(+) group. These data suggest that, compared with those in HIV(+) women, CD4(+) T cells in ESN women have a much greater ability to proliferate in response to p24 peptides.

Widowhood in the era of HIV/AIDS: a case study of Siaya District, Kenya.
Author: Ambasa-Shisanya, C. R.
Source: SAHARA J. 2007 Aug; 4(2):606-15.
Abstract: Luo women are believed to acquire contagious cultural impurity after the death of their husbands that is perceived as dangerous to other people. To neutralise this impure state, a sexual cleansing rite is observed. In the indigenous setting, the ritual was observed by a brother-in-law or cousin of the deceased husband through a guardianship institution. However, with the emergence of HIV/AIDS, many educated brothers-in-law refrain from the practice and instead hire professional cleansers as substitutes. If the deceased spouses were HIV positive, the ritual places professional cleansers at risk of infection. Thereafter, they could act as a bridge for HIV/AIDS transmission to other widows and to the general population. This paper provides insights into reasons for continuity of widowhood rites in Siaya District. Twelve focus group discussions and 20 in-depth interviews were conducted.The cultural violence against Luo widows could spread HIV/AIDS, but Christianity and condoms act as coping mechanisms.
Evidence for expression of endogenous retroviral sequences on primate reproductive tissues and detection of cross-reactive ERVS antigens in the baboon ovary: a review.
Author: Arimi, M. M.; Nyachieo, A.; Langat, D. K.; Abdi, A. M., and Mwenda, J. M..
Source: East Afr Med J. 2006 Feb; 83(2):106-12.
Abstract: Objective:

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.


Data sources:

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


Data synthesis:

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.


Results:

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.


Conclusion:

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



Behaviour change in clients of health centre-based voluntary HIV counselling and testing services in Kenya.
Author: Arthur, G.; Nduba, V.; Forsythe, S.; Mutemi, R.; Odhiambo, J., and Gilks, C..
Source: Sex Transm Infect. 2007 Dec; 83(7):541-6.
Abstract: Objective:

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.


Design and setting:

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.


Subjects: Consecutive eligible adult clients.
Main outcome measures:

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


Results:

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.


Conclusion:

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.



Potential impact of infant feeding recommendations on mortality and HIV-infection in children born to HIV-infected mothers in Africa: a simulation.
Author: Atashili, J.; Kalilani, L.; Seksaria, V., and Sickbert-Bennett, E. E.
Source: BMC Infect Dis. 2008; 8:66.
Abstract: Background:

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.


Methods:

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.


Results:

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.


Conclusion:

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.



Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women.
Author: Baeten, J. M.; Benki, S.; Chohan, V.; Lavreys, L.; McClelland, R. S.; Mandaliya, K.; Ndinya-Achola, J. O.; Jaoko, W., and Overbaugh, J. Kenyan women.
Source : AIDS. 2007 Aug 20; 21(13):1771-7.
Abstract: Background:

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.


Objective:

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.


Methods:

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.


Results:

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).


Conclusions:

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



HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads.
Author: Baeten, J. M.; Chohan, B.; Lavreys, L.; Chohan, V.; McClelland, R. S.; Certain, L.; Mandaliya, K.; Jaoko, W., and Overbaugh, J.
Source : J Infect Dis. 2007 Apr 15; 195(8):1177-80.
Abstract: We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.0-5.6]) and a faster rate of CD4 cell count decline (P=.003). The mortality risk persisted after adjustment for plasma HIV-1 load. There were no differences in plasma viral load by HIV-1 subtype during follow-up. HIV-1 subtype D infection is associated with a >2-fold higher risk of death than subtype A infection, in spite of similar plasma HIV-1 loads.

Female-to-male infectivity of HIV-1 among circumcised and uncircumcised Kenyan men.
Author: Baeten, J. M.; Richardson, B. A.; Lavreys, L.; Rakwar, J. P.; Mandaliya, K.; Bwayo, J. J., and Kreiss, J. K.
Source : J Infect Dis. 2005 Feb 15; 191(4):546-53.
Abstract: Background:

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.


Methods:

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.


Results:

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.


Conclusions:

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.



Polymorphisms in IRF-1 associated with resistance to HIV-1 infection in highly exposed uninfected Kenyan sex workers.
Author: Ball, T. B.; Ji, H.; Kimani, J.; McLaren, P.; Marlin, C.; Hill, A. V., and Plummer, F. A.
Source : AIDS. 2007 May 31; 21(9):1091-101.
Abstract: Objective:

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


Design:

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.


Methods:

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.



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