Dalton Wamalwa

Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children

Objectives:To describe the early response to World Health Organization (WHO)-recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line highly active antiretroviral therapy (HAART) in HIV-1-infected Kenyan children unexposed to nevirapine. Design:Observational prospective cohort. Methods:HIV-1 RNA level, CD4 lymphocyte count, weight for age z score, and height for age z score were measured before the initiation of HAART and every 3 to 6 months thereafter. Children received no nutritional supplements. Results:Sixty-seven HIV-1-infected children were followed for a median of 9 months between August 2004 and November 2005. Forty-seven (70%) used zidovudine, lamivudine (3TC), and an NNRTI (nevirapine or efavirenz), whereas 25% used stavudine (d4T), 3TC, and an NNRTI. Nevirapine was used as the NNRTI by 46 (69%) children, and individual antiretroviral drug formulations were used by 63 (94%), with only 4 (6%) using a fixed-dose combination of d4T, 3TC, and nevirapine (Triomune; Cipla, Mumbai, India). In 52 children, the median height for age z score and weight for age z score rose from −2.54 to −2.17 (P < 0.001) and from −2.30 to −1.67 (P = 0.001), respectively, after 6 months of HAART. Hospitalization rates were significantly reduced after 6 months of HAART (17% vs. 58%; P < 0.001). The median absolute CD4 count increased from 326 to 536 cells/μL (P < 0.001), the median CD4 lymphocyte percentage rose from 5.8% before treatment to 15.4% (P < 0.001), and the median viral load fell from 5.9 to 2.2 log10 copies/mL after 6 months of HAART (P < 0.001). Among 43 infants, 47% and 67% achieved viral suppression to less than 100 copies/mL and 400 copies/mL, respectively, after 6 months of HAART. Conclusion:Good early clinical and virologic response to NNRTI-based HAART was observed in HIV-1-infected Kenyan children with advanced HIV-1 disease.

Herpes simplex virus type 2 and risk of intrapartum human immunodeficiency virus transmission.

OBJECTIVE: To determine whether herpes simplex virus type 2 (HSV-2) infection was associated with risk of intrapartum human immunodeficiency virus type 1 (HIV-1) transmission and to define correlates of HSV-2 infection among HIV-1-seropositive pregnant women. METHODS: We performed a nested case control study within a perinatal cohort in Nairobi, Kenya. Herpes simplex virus type 2 serostatus and the presence of genital ulcers were ascertained at 32 weeks of gestation. Maternal cervical and plasma HIV-1 RNA and cervical HSV DNA were measured at delivery. RESULTS: One hundred fifty-two (87%) of 175 HIV-1-infected mothers were HSV-2-seropositive. Among the 152 HSV-2-seropositive women, nine (6%) had genital ulcers at 32 weeks of gestation, and 13 (9%) were shedding HSV in cervical secretions. Genital ulcers were associated with increased plasma HIV-1 RNA levels (P=.02) and an increased risk of intrapartum HIV-1 transmission (16% of transmitters versus 3% of nontransmitters had ulcers; P = .003), an association which was maintained in multivariable analysis adjusting for plasma HIV-1 RNA levels (P=.04). We found a borderline association for higher plasma HIV-1 RNA among women shedding HSV (P=.07) and no association between cervical HSV shedding and either cervical HIV-1 RNA levels or intrapartum HIV-1 transmission (P=.04 and P=.05, respectively). CONCLUSION: Herpes simplex virus type 2 is the leading cause of genital ulcers among women in sub-Saharan Africa and was highly prevalent in this cohort of pregnant women receiving prophylactic zidovudine. After adjusting for plasma HIV-1 RNA levels, genital ulcers were associated with increased risk of intrapartum HIV-1 transmission. These data suggest that management of HSV-2 during pregnancy may enhance mother-to-child HIV-1 prevention efforts. LEVEL OF EVIDENCE: II

Reasoning and deciding PMTCT-adherence during pregnancy among women living with HIV in Kenya

This study explores type identities among rural and urban slum women on antiretroviral therapies who become pregnant. Narrative structuring was chosen to develop type narratives that illustrate how rural and urban women handle their HIV-infection and how they reason and decide about PMTCT-adherence during pregnancy and childbirth. Women in rural areas described their lives as ‘secure and family controlled’. This gave the women security and predictability in life, but also meant that it was difficult to keep secrets about HIV infection. For women in the urban slum area the narratives were a tale of the uncertain and hard to predict reality in the slum, but also about self-reliance and decisiveness. They portrayed themselves as ‘vulnerable and striving to survive’ thus managing a tough situation without long-term solutions. We conclude that pregnancy poses different social challenges in rural and urban areas affecting how women choose to manage their adherence to PMTCT, which is also affected by HIV stigma and lack of disclosure.

Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre- and post-highly active antiretroviral therapy and revaccination.

Background: HIV-1-infected children have lower response rates after measles and tetanus immunization than uninfected children. We determined the extent to which highly active antiretroviral therapy (HAART) augments vaccine immunity and promotes responses to revaccination. Methods: Previously immunized, antiretroviral-naive HIV-1-infected children were evaluated for immunity against measles and tetanus. After 6 months on HAART, children meeting CD4% criteria (>15%) who were persistently antibody negative were revaccinated and immunity was reassessed. Results: At enrollment, among 90 children with mean age of 4.9 years, 67% had negative measles IgG and 22% negative tetanus IgG. Among 62 children completing 6 months on HAART, 17 (40%) of 43 without protective measles IgG converted and 10 (53%) of 19 positive children lost measles responses (P = 0.3). Children who lost responses had significantly lower measles antibody concentrations than those who remained measles IgG positive during follow-up (7.1 vs. 20.3 mg/mL; P = 0.003). Three (23%) of 13 children negative for tetanus IgG spontaneously seroconverted on HAART, while 15 (31%) of 49 children lost tetanus antibody (P = 0.008). There was a nonsignificant trend for an association between spontaneous measles seroconversion and lower baseline HIV-1 viral load (P = 0.06). Tetanus seroconversion was associated with older age (P = 0.03). After revaccination, positive responses were observed in 78% and 75% of children reimmunized against measles and tetanus, respectively. Conclusions: After 6 months of HAART, more than half of previously immunized children still lacked positive measles antibody. With increased use of HAART in pediatric populations, revaccination against measles and tetanus should be considered to boost response rates and immunization coverage.

Prevalence, perceptions, and correlates of pediatric HIV disclosure in an HIV treatment program in Kenya.

Disclosure to HIV-infected children regarding their diagnosis is important as expanding numbers of HIV-infected children attain adolescence and may become sexually active. In order to define correlates of pediatric disclosure and facilitate development of models for disclosure, we conducted a cross-sectional survey of primary caregivers of HIV-1 infected children aged 6–16 years attending a pediatric HIV treatment program in Nairobi, Kenya. We conducted focus group discussions with a subset of caregivers to further refine perceptions of disclosure. Among 271 caregiver/child dyads in the cross-sectional survey, median child age was 9 years (interquartile range: 7–12 years). Although 79% of caregivers believed children should know their HIV status, the prevalence of disclosure to the child was only 19%. Disclosure had been done primarily by health workers (52%) and caregivers (33%). Caregivers reported that 5 of the 52 (10%) who knew their status were accidentally disclosed to. Caregivers of older children (13 vs. 8 years; p<0.001), who were HIV-infected and had disclosed their own HIV status to the child (36% vs. 4%; p=0.003), or who traveled frequently (29% vs. 16%, p=0.03) were more likely to have disclosed. Children who had been recently hospitalized (25% vs. 44%, p=0.03) were less likely to know their status, and caregivers with HIV were less likely to have disclosed (p=0.03). Reasons for disclosure included medication adherence, curiosity or illness while reasons for nondisclosure included age and fear of inadvertent disclosure. Our study found that disclosure rates in this Kenyan setting are lower than observed rates in the USA and Europe but consistent with rates from other resource-limited settings. Given these low rates of disclosure and the potential benefits of disclosure, strategies promoting health worker trainings and caregiver support systems for disclosure may benefit children with HIV.

Latent Tuberculosis Detection by Interferon γ Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1-Infected Women and Their Children

BACKGROUND We evaluated the prognostic usefulness of interferon γ release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants. METHODS Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHR(CD4)), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants. RESULTS Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHR(CD4), 4.5; 95% confidence interval [CI], 1.1-18.0; P = .030). For immunosuppressed women (CD4 cell count, <250 cells/μL), positive IGRA results were associated with increased risk of maternal mortality (aHR(CD4), 3.5; 95% CI, 1.02-12.1;), maternal active tuberculosis or mortality (aHR(CD4), 5.2; 95% CI, 1.7-15.6; P = .004), and infant active tuberculosis or mortality overall (aHR(CD4), 3.0; 95% CI, 1.0-8.9; P = .05) and among HIV-1-exposed uninfected infants (aHR(CD4), 7.3; 95% CI, 1.6-33.5; P = .01). CONCLUSIONS Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants.

High uptake of postpartum hormonal contraception among HIV-1-seropositive women in Kenya.

Objectives: The objectives of this study were to determine patterns of contraceptive utilization among sexually active HIV-1-seropositive women postpartum and to identify correlates of hormonal contraception uptake. Goal: The goal of this study was to improve delivery of family planning services to HIV-1-infected women in resource-limited settings. Study Design: HIV-1-infected pregnant women were followed prospectively in a perinatal HIV-1 transmission study. Participants were referred to local clinics for contraceptive counseling and management. Results: Among 319 HIV-1-infected women, median time to sexual activity postpartum was 2 months and 231 (72%) women used hormonal contraception for at least 2 months during follow-up, initiating use at approximately 3 months postpartum (range, 1–11 months). Overall, 101 (44%) used DMPA, 71 (31%) oral contraception, and 59 (25%) switched methods during follow-up. Partner notification, infant mortality, and condom use were similar between those using and not using contraception. Conclusions: Using existing the healthcare infrastructure, it is possible to achieve high levels of postpartum hormonal contraceptive utilization among HIV-1-seropositive women.

Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up.

Background:Much of the burden of morbidity affecting women of childbearing age in sub-Saharan Africa occurs in the context of HIV-1 infection. Understanding patterns of illness and determinants of disease in HIV-1-infected mothers may guide effective interventions to improve maternal health in this setting. Methods:We describe the incidence and cofactors of comorbidities affecting peripartum and postpartum HIV-1-infected women in Kenya. Women were evaluated by clinical examination and standardized questionnaires during pregnancy and for up to 2 years after delivery. Results:Five hundred thirty-five women were enrolled in the cohort (median CD4 count of 433 cells/mm3) and accrued 7736 person-months of follow-up. During 1-year follow-up, the incidence of upper respiratory tract infections was 161 per 100 person-years, incidence of pneumonia was 33 per 100 person-years, incidence of tuberculosis (TB) was 11 per 100 person-years, and incidence of diarrhea was 63 per 100 person-years. Immunosuppression and HIV-1 RNA levels were predictive for pneumonia, oral thrush, and TB but not for diarrhea; CD4 counts <200 cells/mm3 were associated with pneumonia (relative risk [RR] = 2.87, 95% confidence interval [CI]: 1.71 to 4.83), TB (RR = 7.14, 95% CI: 2.93 to 17.40) and thrush. The risk of diarrhea was significantly associated with crowding (RR = 1.86, 95% CI: 1.19 to 2.92) and breast-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). Less than 10% of women reported hospitalization during 2-year follow-up; mortality risk in the cohort was 1.9% and 4.8% for 1 and 2 years, respectively. Conclusions:Mothers with HIV-1, although generally healthy, have substantial morbidity as a result of common infections, some of which are predicted by immune status or by socioeconomic factors. Enhanced attention to maternal health is increasingly important as HIV-1-infected mothers transition from programs targeting the prevention of mother-to-child transmission to HIV care clinics.

Survival benefit of early infant antiretroviral therapy is compromised when diagnosis is delayed

Late presentation is common among African HIV-1–infected infants. Incidence and correlates of mortality were examined in 99 infants with HIV-1 diagnosis by 5 months of age. Twelve-month survival was 66.8% (95% confidence interval: 55.9–75.6%). World Health Organization stage 3 or 4, underweight, wasting, microcephaly, low hemoglobin, pneumonia and gastroenteritis predicted mortality. Early HIV-1 diagnosis with antiretroviral therapy before symptomatic disease is critical for infant survival.

Illness during pregnancy and bacterial vaginosis are associated with in-utero HIV-1 transmission.

HIV-1 transmission in utero accounts for 20–30% of vertical transmission events in breast-feeding populations. In a prospective study of 463 HIV-1-infected mothers and infants, illness during pregnancy was associated with 2.6-fold increased risk of in-utero HIV-1 transmission [95% confidence interval (CI) 1.2–5.8] and bacterial vaginosis with a three-fold increase (95% CI 1.0–7.0) after adjusting for maternal HIV-1 viral load. Interventions targeting these novel risk factors could lead to more effective prevention of transmission during pregnancy.