An evaluation of the early effects of a combination antiretroviral therapy programme on the management of AIDS-associated Kaposi's sarcoma in KwaZulu-Natal, South Africa.

Roll-out of combination antiretroviral therapy (cART) in South Africa should impact on AIDS-associated Kaposi's sarcoma (KS). Government provision began in 2003, with 23% coverage for World Health Organization (WHO) stage IV AIDS in 2006. To assess the effect of cART availability on KS management, we evaluated records from 701 KS patients seen at a tertiary oncology centre in KwaZulu-Natal, South Africa, from 1995 to 2006. Associations between cART use and measures of KS care were evaluated. cART availability was 0% prior to 2001, 9.6% (2001-2003) and 44% (2004-2006). Documentation of HIV status increased incrementally from 65% to 92%. cART was associated with chemotherapy administration: 56% on cART versus 17% not on cART (P < 0.001); and less loss to follow-up, 13% on cART versus 38% not on cART (P < 0.001). cART availability improves the care of AIDS-associated KS. Further increases in cART availability for this population are needed in South Africa.

Increasing incidence of Kaposi's sarcoma in black South Africans in KwaZulu-Natal, South Africa (1983-2006).

The aim of the study was to describe the temporal trends in the incidence of Kaposi's sarcoma (KS) in black South Africans in KwaZulu-Natal (KZN). The study was designed as a retrospective record review. The incidence of Kaposi's sarcoma was estimated using administrative records for patients receiving care for KS through public sector oncology clinics in KZN, 1983-2006. Annual age-standardized incidence rates were calculated using provincial census data for the denominator. Age-specific rates were calculated for the pre-AIDS (1983-1989) and for the generalized AIDS epidemic eras (2006). Age-standardized incidence of KS increased in KZN from <1:100,000 in 1990 to at least 15:100,000 in 2006; this increase was observed in both men and women. There was a shift in the peak age-specific incidence rates from the sixth decade of life in the pre-AIDS era to the fourth and fifth decades in the AIDS era. In conclusion, KS is a growing public health problem in KZN, South Africa. These data reinforce the need for comprehensive national access to and roll-out of antiretroviral drugs, given their success in prevention and treatment of KS in first-world settings.

Rapid testing may not improve uptake of HIV testing and same day results in a rural South African community: a cohort study of 12,000 women.

BACKGROUND: Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area. METHODS AND PRINCIPAL FINDINGS: HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT) programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6%) and 4,810 (74.6%) agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4%) requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p<0.001), as were women aged 21-35 (AOR 0.762, p<0.001) and >35 years (AOR 0.756, p<0.01) compared to those <20 years. CONCLUSIONS: Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given.

Characteristics of HIV-1-associated Kaposi's sarcoma among women and men in South Africa.

Despite the increase of HIV-1-associated Kaposi's sarcoma (KS), little is known about HIV-associated KS in the African setting, particularly among women. A descriptive study of the demographic, clinical, immunological and virological features of AIDS-associated KS from KwaZulu-Natal, South Africa was undertaken. Consecutively, recruited patients were clinically staged; CD4/CD8 cell counts, HIV-1 viral loads and clinical parameters were evaluated. Of the 152 patients (77 male and 75 female) 99% were black. Females were significantly younger (P = 0.02) and had poorer disease prognosis (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4, P = 0.003) and were more likely to have extensive cutaneous KS when compared with males (OR = 3.1, 95% CI = 1.4-6.7, P = 0.003). One-third of patients had coexisting HIV-related disease, most commonly tuberculosis, and these were more frequent in females (56.7 vs. 43.3%). In conclusion, HIV-associated KS in South Africans has an equal female-to-male ratio. Females are younger and have more severe disease than males.

Messages about dual contraception in areas of high HIV prevalence are not heeded.

BACKGROUND: Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections, including HIV. It is critical for HIV-negative women to prevent seroconversion and HIV transmission to their infants during pregnancy and breastfeeding. METHODS: Women were followed up after delivery, monthly for the first 9 months and then 3-monthly to 24 months, in a cohort study investigating postnatal HIV transmission. Study nurses discussed family planning, including condom use, at each visit. Contraceptive methods used since the last visit were recorded. All women knew their HIV status, and most women breastfed for a minimum of 6 months. RESULTS: Among 1,137 HIV-positive and 1 220 HIV-negative women the most common contraceptive method was the hormonal injectable; few women used condoms alone or as dual contraception (0-3 months 6.8%; 7-12 months 16.3%; 19-24 months 14.4%). Compared with uninfected women, HIV-positive women were more likely to use condoms in years 1 and 2 after delivery (adjusted odds ratio (AOR) 1.72, 95% confidence interval (CI) 1.38-2.14, p<0.001; AOR 1.61, 95% CI 1.15-2.25, p=0.006 respectively). Compared with women with a flush toilet, those with a pit latrine were less likely to use condoms in years 1 and 2 (AOR 0.22, 95% CI 01.7-0.28, p<0.001; AOR 0.27, 95% CI 0.19-0.39, p<0.001). Older women were more likely to use condoms in the first postpartum year (AOR 1.78, 95% CI 1.03-3.09, p=0.040). CONCLUSIONS: More creative ways of promoting condoms and dual contraception need to be found if new HIV infections, in women and children, are to be prevented.

Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.

In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 ( n = 259) expression are associated with differences in HIV-1-specific CD8 (+) T cell responses. The overall breadth and magnitude of HIV-1-specific CD8(+) T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801-restricted CD8 (+) T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8 (+) T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression.

Messages about Dual Contraception in Areas of High HIV Prevalence are not Heeded

Background : Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections; including HIV. It is critical for HIV-negative women to prevent sero-conversion and HIV transmission to their infants during pregnancy and breastfeeding. Methods: Women were followed post-partum; monthly to 9 months and 3-monthly to 24 months; in a cohort study investigating postnatal HIV transmission. Study nurses discussed family planning; including condom use; at each visit. Contraceptive methods used since the last visit were recorded. All women knew their HIV status; most women breastfed for a minimum of six months.Results : of 1137 HIV-positive and 1220 HIV-negative women the most common contraceptive method was the hormonal injectable; few women used condoms alone or as dual contraception (0-3 months 6.8; 7-12 months 16.3; 19-24 months 14.4). HIV-positive women were more likely to use condoms in years one and two post-partum (AOR 1.72; 95CI 1.38-2.14; pp=0.040). Conclusions. More creative ways of promoting condoms and dual contraception need to be found if new HIV infections; in women and children; are to be prevented

Breast health problems are rare in both HIV-infected and HIV-uninfected women who receive counseling and support for breast-feeding in South Africa.

BACKGROUND: Breast problems, including mastitis, can interfere with the duration and exclusivity of breast-feeding. However, there are no large prospective studies documenting the prevalence, duration, and timing of such problems in breast-feeding women, particularly those who are infected with human immunodeficiency virus (HIV). METHODS: Women enrolled prenatally underwent a breast-feeding counseling intervention until 6 months after delivery. Breast health problems were documented per breast for 180 days after delivery, with 14-day recall histories. RESULTS: Breast health problems were rare, and there were no significant differences between HIV-infected and HIV-uninfected women for any of the following conditions: engorgement, 39 HIV-infected women (3.5%) versus 33 HIV-uninfected women (2.7%; P=.30); breast thrush, 17 (1.5%) versus 12 (1.0%; P=.25); bleeding nipple, 6 (0.5%) versus 4 (0.3%; P=.45); and mastitis/abscess, 11 (1.0%) versus 6 (0.5%; P=.17). Most problems occurred during the first month after birth, with few additional mothers experiencing problems after this point: at 1 and 6 months, 13% and 17% of all mothers, respectively, had experienced a minor or major breast health problem, including sore nipples. Women who had not exclusively breast-fed their infants were more likely to experience any of the breast health problems than were women who had exclusively breast-fed their infants (time-dependent variable; adjusted odds ratio, 1.46; 95% confidence interval, 1.13-1.87; P=.003). HIV-infected women who experienced any serious breast health problem (i.e., bleeding nipple, pus oozing from a nipple or breast, or mastitis/abscess) were 3.55 times (95% confidence interval, 0.86-14.78 times; P=.08) more likely to transmit HIV postnatally to their infant. CONCLUSIONS: With encouragement to exclusively breast-feed, women experienced few breast health problems. When those problems did occur, HIV-infected women with bleeding nipple, pus oozing from a nipple or breast, or mastitis/abscess were more likely to transmit HIV to their infants.

Preserving breastfeeding practice through the HIV pandemic.

Breastfeeding, particularly for the first 6 months of life, is unquestionably the ideal way to feed most infants. However, the human immunodeficiency virus (HIV) pandemic has caused debate and confusion about the best way for HIV-positive mothers to feed their children. This review provides recent key findings and opinions around making breastfeeding safer for HIV-positive women, and argues for preservation of breastfeeding, as opposed to complete avoidance of breastfeeding for all HIV-positive women.

Impact of HIV-1 status on the radiological presentation and clinical outcome of children with WHO defined community-acquired severe pneumonia.

AIMS: We compared the radiological features and outcome of WHO defined severe pneumonia among HIV infected and exposed uninfected children randomised to receive penicillin or oral amoxicillin in Durban, South Africa. METHODS: Of 425 children aged between 3 and 59 months with WHO defined severe pneumonia, 366 had anonymous HIV testing performed. Outcome was assessed by failure to improve at 48 h after enrolment or deterioration within 14 days. Chest radiographs were evaluated according to WHO defined radiological criteria for pneumonia and internationally standardised radiological criteria. Findings were stratified for HIV status. RESULTS: 82 (22.4%) children were HIV infected, 40 (10.9%) were HIV exposed and 244 (66.7%) were HIV uninfected. The day 14 outcome in children <12 months of age was significantly worse in HIV-1 infected than HIV uninfected children (OR 2.8 (95% CI 1.35 to 3.5), p = 0.002), while HIV-1 infected and uninfected children aged > or =12 months had equivalent outcomes. Parental penicillin and oral amoxicillin had equivalent response rates in all HIV groups. According to the WHO radiological classification, children who failed WHO standard antimicrobial treatment had significantly higher "other consolidates/infiltrates" than "endpoints for consolidation" in the HIV infected group (OR 5.45 (95% CI 1.58 to 21.38), p<0.002), while the reverse was true for HIV exposed uninfected children (OR 4.13 (95% CI 0.88 to 20.57), p<0.036). CONCLUSIONS: The WHO standard treatment guideline for severe pneumonia is inadequate for HIV-1 infected infants. The increased prevalence of "other consolidates/infiltrates" among HIV-1 infected children who failed standard treatment supports the addition of co-trimoxazole to WHO standard treatment.

Infant feeding counselling for HIV-infected and uninfected women: appropriateness of choice and practice.

OBJECTIVE: To examine infant feeding intentions of HIV-infected and uninfected women and the appropriateness of their choices according to their home resources; and to determine their adherence to their intentions in the first postnatal week. METHODS: Feeding intentions of pregnant women were compared against four resources that facilitate replacement feeding: clean water, adequate fuel, access to a refrigerator and regular maternal income. First-week feeding practices were documented. FINDINGS: The antenatal feeding intentions of 1253 HIV-infected women were: exclusive breastfeeding 73%; replacement feeding 9%; undecided 18%. Three percent had access to all four resources, of whom 23% chose replacement feeding. Of those choosing replacement feeding, 8% had access to all four resources. A clean water supply and regular maternal income were independently associated with intention to replacement feed (adjusted odds ratio (AOR) 1.94, 95% confidence interval (CI) 1.2-3.2; AOR 2.1, 95% CI: 1.2-3.5, respectively). Significantly more HIV-infected women intending to exclusively breastfeed, rather than replacement feed, adhered to their intention in week one (exclusive breastfeeding 78%; replacement feeding 42%; P<0.001). Of 1238 HIV-uninfected women, 82% intended to exclusively breastfeed; 2% to replacement feed; and 16% were undecided. Seventy-five percent who intended to exclusively breastfeed adhered to this intention postnatally, and only 11 infants (<1%) received no breast milk. The number of antenatal home visits significantly influenced adherence to feeding intention. CONCLUSION: Most HIV-infected women did not have the resources for safe replacement feeding, instead choosing appropriately to exclusively breastfeed. Adherence to feeding intention among HIV-infected women was higher in those who chose to exclusively breastfeed than to replacement feed. With appropriate counselling and support, spillover of suboptimal feeding practices to HIV-negative women is minimal.

Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.

Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa.

OBJECTIVES: To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea. DESIGN: A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status. SETTING: Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis. SUBJECTS: Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea. RESULTS: In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10). CONCLUSIONS: This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken.

Challenges in the provision of ICU services to HIV infected children in resource poor settings: a South African case study.

The HIV/AIDS epidemic has placed increasing demands on limited paediatric intensive care services in developing countries. The decision to admit HIV infected children with Pneumocystis carinii pneumonia (PCP) into the paediatric intensive care unit (PICU) has to be made on the best available evidence of outcome and the ethical principles guiding appropriate use of scarce resources. The difficulty in confirming the diagnosis of HIV infection and PCP in infancy, issues around HIV counselling, and the variance in the outcome of HIV infected children with PCP admitted to the PICU in African studies compound this process. Pragmatic decision making will require evaluation of at least three ethical questions: are there clinical and moral reasons for admitting HIV positive children with PCP to the PICU, should more resources be committed to caring for HIV children who require the PICU, and how can we morally choose candidates for the PICU? Those working in the PICU in HIV endemic regions need to make difficult personal decisions on effective triage of admissions of HIV infected children with PCP based on individual case presentation, availability of resources, and applicable ethical principles.

Colloquium report: improving the health of school age children in an era of HIV/AIDS in Durban, South Africa.

Increased morbidity and mortality due to the HIV/AIDS epidemic in South Africa necessitates the examination of policies for the protection and support of school age children. At a colloquium held in Durban participants from government and non-government health and education sectors briefed delegates on key policies and programmes for promoting the health and mental health of school age children. Researchers gave evaluative accounts of the impacts of these measures and presented an overview of South African children's health and mental health needs. In the discussions that followed four critical issues emerged: intersectoral collaboration, accountability, retraining middle management, and a more comprehensive strategy to support pupils and teachers infected and affected by HIV/AIDS.